An Overview of Capillary Electrophoresis Pharmaceutical Biopharmaceutical and Biotechnology Applicat PDF

J Pharm Educ Res Vol. 2, Issue No.
2, December 2011
An overview of capillary electrophoresis: Pharmaceutical,

biopharmaceutical and biotechnology applications
Bhupinder Singh Sekhon
PCTE Institute of Pharmacy, Near Baddowal Cantt. (Ludhiana) -142021, India.
Email:sekhon224@yahoo.com
Received: November 08, 2011; Accepted: November 30, 2011

ABSTRACT
Capillary electrophoresis (CE) is an establishing separation technique of choice effective for a wide spectrum of
analytes, ranging from small inorganic ions to DNA macromolecules as it provides reliable data, requires
minimal sample preparation and offers a high degree of automation. CE is an alternative to more traditional
methods such as gel electrophoresis and liquid chromatography and is employed to detect both high and low
affinity molecular interactions, and separation of both charged and non-charged molecules. CE technique covers
different modes that essentially rely on a high voltage electric field being applied over a solution which is held in
a capillary tube. In CE, the separation is based on charge, size and frictional force and it offers fast separations
with exceptional efficiency. CE has proved to be an efficient and versatile approach for physicochemical
characterization of bioactive molecules and resolution for charged substances such as biomolecules, low molecular
weight basic or acidic drugs and ions. CE is now an established technique in several areas of analysis and is
capable of detecting millimolar to nanomolar binding interactions and offers the benefits of a powerful and
proven technology applied to drug discovery screening on a wide variety of targets such as enzymes, membrane
receptor domains, structural proteins, nucleic acid complexes, bioactive peptides, protein-protein interactions
and antibodies. CE can also determine chiral purity in pharmaceuticals and can be successfully used to support
aspects of early drug discovery and drug development testing, analysis of protein-based pharmaceuticals and
routine quality control of marketed pharmaceuticals. CE has found application in the analysis of complex
carbohydrates and in the increased associated activities of CE-MS techniques in the biotechnology and
biopharmaceutical industry. CE-frontal analysis provided a method on the interaction of drugs with plasma
proteins. Various applications of hyphenated capilliary electrphoresis techniques include characterization of
quantum dots and quantum dots-conjugated biological molecules. Immunoaffinity capillary electrophoresis has
been reported as a versatile tool for determining protein biomarkers in inflammatory processes and for total
Immunoglobulin E quantification in serum. CE technology has been valuable for the comprehensive
characterization of macromolecules, used both as biologics and in proteomic study, and to analyze and characterize
therapeutic proteins in biotechnology.
Keywords: Capillary electrophoresis, glycoproteins, chiral separation, quality control, pharmaceutical, biopharmaceutical,
biotechnology applications.
INTRODUCTION
dimensions of the capillaries greatly increased the surface

to volume ratio, which eliminated overheating by high
voltages. The potential of CE as a high-resolution
analytical separation technique was first described in 1981
using glass capillary column and aqueous buffer to
separate charged compounds 4. CE technology employs
narrow-bore capillaries to perform electrophoresis in free
solution or nonconductive medium, such as a gel and can
detect both high and low affinity molecular interactions
covering both large and small molecules 5-7. The typical
voltages employed in the region of 10-30 kV across a
capillary with a bore diameter of about 25-100mu give
rise to operational currents in the region of 10-100
microamps. A brief history of CE is given in Table 1.
Electrophoresis is the migration of ions or solutes

under the influence of an electric field. Capillary
electrophoresis (CE) is electrophoresis performed in a
capillary tube and is the most efficient separation technique
available for the analysis of both large and small molecules
1-3
. CE is an analytical technique that separates ions based
on their electrophoretic mobility with the use of an applied
voltage. The electrophoretic mobility is dependent upon
the charge of the molecule, the viscosity, and the atoms
radius. The rate at which the particle moves is directly
proportional to the applied electric fieldthe greater the
field strength, the fast the mobility. In CE, the thin
2
J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

Table. 1. A brief history of CE.
Reference
Year
Discovery event
1967
First high voltage CE system (with rotating 3 mm internal diameter capillaries.
1981
CE was first described in 1981 by Jorgenson and Lukacs. These researchers demonstrated highly efficient
electrophoresis separations of peptide by performing electrophoresis in narrow bore capillaries filled with buffer,
normally in the range from 25 to 100 m of internal diameter.
1983
The first paper on capillary gel electrophoresis was published in the 80s by Hjertn.
10
1984
Isoelectric focussing was introduced in capillary format
11
1984
Micellar electrokinetic chromatography, a hybrid of electrophoresis and chromatography was introduced by

Terabe.
12
13
1985
Anionic micelles were used as a pseudostationary phase to separate neutral compounds.
1987
Karger and co-workers addressed the application area of protein separations in polyacrylamide gels in the presence
of sodium dodecyl sulphate (SDS).
14,15
19871989
The first automated CE instrument was introduced commercially under the name Microphoretic 1000 by
Microphoretic Systems (Sunnyvale, CA, USA) in 1987. Second by Applied Biosystems (Foster City, CA) in
1988. In 1989, Beckman Instruments introduced the first fully automated capillary electrophoresis instrument (P/
ACE 2000)
16
1987
Capillary electrochromatography (CEC) in open tubular columns and detailed theoretical analysis of
electrochromatography and technique development.
17,18
1988
Kargers group shows DNA separations of single strandedoligonucleotides with gel-filled capillaries.
19
1989
Bob Brownlee and coworkers introduced the first commercial instrument with on column UV/VIS detection,
automatic injection and computerized data analysis for rapid, high-resolution CE separation.
20
1989
Beckman Coulter (then Beckman Instruments) introduced the first fully automated capillary electrophoresis
system the P/ACE 2000.
21
19901993
Karger s group shows DNA separations with sieving polymers on DNA restriction fragments.
22-24
1990
Various workers presented the reports of capillary array electrophoresis for DNA sequencing.
25-28
1991
The capillary column packed with particulate stationary phase, which generally consists of inorganic particles
(silica beads) allows high loading capacity.
29
1991
Grossman expands work with sieving polymers.
30
1991
Everaerts demonstrated the use of isotachophoresis in open tubular fused silica capalliaries.
31
1992
Mathies et al. developed the approach of multiplexing the separation of DNA sequencing fragments by means of
the use of arrays of capillaries. This was a significant and necessary development in capillary based DNA sequencing,
leading to a 96-column format as the method of choice for production-scale work.
32
1994
The potential of CEC in the analysis of mixtures relevant to the pharmaceutical industry was realized by Smith and
Evans.
33
1995
The most important CE techniques and their use for the analysis and characterization of proteins and DNA.
34
1996
Rapid and automated genetic typing using capillary electrophoresis for the analysis of short tandem repeats
(STRs).
35
2001
Conditions for typing PCR-amplified short tandem repeat (STR) loci by capillary electrophoresis were investigated
using the ABI Prism 310 Genetic Analyzer.
36
2004
High-resolution CE provides an alternative for rapid identification of Mycobacterium species.
37
2005
An overview over quantitative measurements performed by CE-MS.
38
2008
CE coupled with laser-induced fluorescence was used for the characterization of quantum dots and their conjugates
to biological molecules.
39
2009
Papers detailing the use of affinity capillary electrophoresis in examining binding parameters between biological
species.
40
2011
Beckman Coulter introduced the CESI 8000 High Performance Separation-ESI Module with OptiMS technology
consisting of the first commercial CESI sprayer combined with new capillary electrophoresis instrumentation
specifically designed for mass spectrometry (MS). CESI is the integration of CE and ESI by a dynamic process
41

within a single device; Agilent Technologies Launches Automated Electrophoresis System to Accelerate Sample
and Library QC for Next-Generation Sequencing
2011
Dr. Stellan Hjertn, the Father of Capillary Electrophoresis, received the 2011 award at CASSS Annual Award
Dinner on November 3, 2011 in Oakland, California. Dr. Hjertn has done pioneering work in many branches of
separation science, introducing agarose gels for electrophoresis and polyacrylamide gels for chromatography and
using them for chromatography and electrophoresis.
42
2011
Rogers et al. demonstrated the use of microstructured fibres for capilliary zone electrophoresis, taking advantage
of their relatively high surface-to-volume ratio and the small individual size of each channel to effect highly efficient
separations, particularly for dye-labelled peptides.
43
Advantages over HPLC
/Capillary electrochromatography (CEC)
Qualities of CE such as high efficiency of separation,

short analysis time, remarkably low injection volume, the
possibility of chiral separation without the need of special
expensive columns, ease of operation and a variety of
detection systems have facilitated acceptance of this
technology 44. One of the major advantages of CE over
other separation technique is the ability to separate both
charged and non-charged molecules. CE offers several
advantages over high-pressure or high-performance liquid
chromatography (HPLC). These include simplicity, rapid
analysis, automation, ruggedness, different mechanisms
for selectivity, and low cost 45. Separation mode in HPLC
is determined by column stationary phase and mobile
phase, however, separation mode in CE is determined
only by buffer and one type of capillary can be used for
different modes of separations. CE also uses aqueous
rather than organic solvents and is thus environmentally
friendlier than HPLC 46-48.
v)
Micellar electrokinetic chromatography (MEKC)
vi)
Microemulsion electrokinetic chromatography

(MEEKC)
vii)
Capillary isoelectric focusing (CIEF)
viii)
Capillary isotachophoresis (CITP)
ix)
Pressurized capillary electrochromatography

(pCEC)
x)
Affinity capillary electrophoresis (ACE)
xi)
Imunoaffinity capillary electrophoresis (IACE)
xii)
Nano capillary electrophoresis (NCE)
xiii)
Microchip-based capillary electrophoresis

(Microchip-based CE)
Various separation modes of CE
In CZE, analytes move in the electroosmotic flow

but separate into bands due to differences in their
electrophoretic mobilities (). Differences in results each
analytes overall migration velocity slightly different, and
difference in migration velocity leads to separation.
Electrophoretic mobilities are roughly a function of analyte
charge and frictional and size differences. CZE is a
separation technique based on charge: mass ratio and is
the most commonly used mode of separation in CE.
Cations with the largest charge-to-mass ratios separate
out first, followed by cations with reduced ratios, neutral
species, anions with smaller charge-to-mass ratios, and
finally anions with greater ratios. This technique is able
to separate both cations and anions in the same run under
high electroosmotic flow (EOF) conditions. The separation
in CZE relies on a constant field strength across the
capillary and the pH of the buffer solution, and then
xiv) Microfluidic capillary electrophoresis (MFCE)

i)
The differential movement for migration of ions by

attraction or repulsion in an electric field separate the
components of a mixture using an electric field v = Eq / f,
where v = velocity of molecule E = electric field, q = net
charge of molecule, and f = friction coefficient. CE is an
umbrella term for many different methods. The process
of capillary electrophoresis is actually a generic term and
depending on the types of capillary and electrolytes used,
the technology of CE can be segmented into several
separation techniques. Examples of these include:
i)
Capillary zone electrophoresis (CZE)
ii)
Nonaqueous capillary electrophoresis (NACE)
iii)
Capillary gel electrophoresis (CGE)
iv)
Capilliary electrokinetic chromatography (CEKC)

4
Capillary zone electrophoresis (CZE)
biological macromolecules such as oligonucleotides, DNA

restriction fragments and proteins 66-70. An overview of
uncommon replaceable matrices (gels) containing
saccharides, newly developed acrylamide-based gels and
thermoadjustable viscosity polymers, namely triblock
copolymers and grafted polyacrylamide for CGE were
reported 71. Researchers have described the development
of a method that uses CGE to analyze mixtures of inorganic
polyphosphate (Pi)n. Resolution of (Pi)n on the basis of n,
the number of residues of dehydrated phosphate, is
accomplished by CGE using capillaries filled with solutions
of poly(N,N-dimethylacrylamide) to exploit sieving
properties of low-viscosity solutions of PDMA and indirect
detection by the UV absorbance of a chromophore,
terephthalate, added to the running buffer 72. Researchers
developed a picoliter-scale partial translational
spontaneous injection approach for high-speed protein
separation under sodium dodecyl sulphate (SDS)-CGE
mode. In this context, a high-speed CE system for protein
separation based on a short capillary and slotted-vial array
has the advantages of simple structure, ease of building
without the requirement of microfabricated devices,
convenient operation, and low cost. Five fluorescein
isothiocyanate labeled proteins including myoglobin, egg
albumin, bovine serum albumin, phosphorylase b, and
myosin were separated within 60s with an effective
separation length of 1.5 cm. Moreover, the separation
speed and separation efficiency of the present system
were comparable to those of most microchip-based
capillary electrophoresis systems for protein separation73.
ultimately on the differences in analytes electrophoretic

mobilities that result in different velocities of migration of
ionic species 49,50. In CZE, different types of chiral
selectors including cyclodextrins, oligo- and
polysaccharides, crown ethers, macrocyclic antibiotics,
ligand exchange systems and proteins are employed 51,52.
Protein isoforms with small pI differences were rapidly
analyzed using CZE with new dynamic coatings 53. The
Sebia CAPILLARYS CDT system proved a simple
and reliable method to screen for Congenital Disorders
of Glycosylation in pediatric and adult patients with an
unexplained clinical syndrome 54. CZA method was
successfully applied to determination of sparfloxacin in
pharmaceutical tablets 55.
ii) Nonaqueous capillary electrophoresis (NACE)
Nonaqueous capillary electrophoresis (NACE) is a
process similar to CZA which is useful in the separation
of compounds that are insoluble in water as it relies mainly
on the use of organic solvents. The viscosity and dielectric
constants of organic solvents affect both sample ion
mobility and the level of electro osmotic flow. NACE is
undergoing rapid development 56 as the use of non-aqueous
medium allows additional selectivity options in methods
development 57. Chiral separations of pharmaceutical
racemic amines were achieved by NACE using various
cyclodextrins 58-61. Researchers demonstrated UV- and
mass-spectrometric detection of enantiomeric amines
resolved by NACE 62. A simple enantioselective method
based on CE using cyclodextrins as chiral selector was
found to be appropriate for controlling pharmaceutical
formulations containing isradipine enantiomers 63. The
NACE proved as the best CE technique out of CZE,
MEKC and MEEKC employed for the determination of
impurities in bromazepam, as its low solubility in water
was easily overcome 64. NACE has been widely used in
pharmaceutical and the recent advances in the applications
of NACE were reported 65.
CGE was used for the rapid separation of SDSprotein complexes according to their molecular masses
and a linear relationship between migration time and log
molecular masses was found 74. The application of a SDSCGE method for the analysis of triple 2/6/7 and doublelayered 2/6 rotavirus-like particles , candidate vaccines
against rotavirus infection has been reported. SDS-CGE
analysis of rotavirus-like particles resulted in peaks that
could be attributed to the viral proteins (VP2, VP6 and
VP7) according to their apparent molecular mass75.
Researches described microchannel-based SDS-CGE of
proteins and demonstrated its speed and high resolution76.
SDS-CGE is not widely accepted in proteomic research
primarily due to the difficulties in identifying the wellresolved proteins. Poly(tetrafluoroethylene) membranes
are excellent materials for collecting SDS-CGE-separated
iii) Capillary gel electrophoresis (CGE)

Capillary gel electrophoresis (CGE) ability to separate
molecules accurately and consistently relies on a constant
field strength across the capillary and the pH of the buffer
solution, and then ultimately on the charge/mass ratio of
the molecules. CGE separation is based on the difference
in solute size as the particles migrate through the gel. CGE
is used for the size and shape-based separation of
5
proteins. Scientists demonstrated the SDS washing bound

to the collected proteins and identified these proteins on
membrane with MALDI-TOF-MS 77. A capillary sodium
dodecyl sulfate gel electrophoresis (cSDS-CGE) method
for the analysis of monoclonal antibody (mAb1) under
reduced and non-reduced conditions was found to be
linear, accurate, and precise in the range of 0.253.0 mg/
mL protein concentration 78,79.
and have been used for pharmaceutical applications

including analysis of steroid isomers 88,89.
The fast separation of chiral !-blockers on a cellulose
tris(3,5-dimethylphenylcarbamate) (CDMPC)-modified
zirconia monolithic column by CEC was reported. The
porous zirconia monolithic capillary column was prepared
by using the sol-gel technology and then zirconia surface
modified with CDMPC 90. The separation of acidic and
basic compounds on monolithic columns demonstrated
CEC separation protocol. An on-line concentration
technique in CEC was reported. As a result of the
coexistence of stationary phase and electric field in a CEC
column, it is possible to employ chromatographic zone
sharpening and field-amplified sample stacking effects
simultaneously to improve CEC detection sensitivity 91.
The determination of drug partition in membrane
phospholipids 92 and the recent applications in
enantioselective analysis by means of CEC were reported
93
.
CGE can be used as an accurate and high throughput

diagnostic procedure for mutational status in the CEBPA
gene identifying not only the same mutational frequency
as in the published reports but also the TAD2C
polymorphism in addition 80.
iv) Capillary electrokinetic chromatography
(CEKC)/ Capillary electrochromatography (CEC)
CE technique with development of CEKC and
recently CEC are separation technique based on a
combination of liquid chromatographic and electrophoretic
separation methods. CEC offers both the efficiency of
CE and the selectivity and sample capacity of packed
capillary HPLC. CEC capillaries accommodate relatively
large amounts of sample due to high surface area of these
packing materials, thereby, making detection a simpler
task than it is in CE 81. Both CEKC and CEC enable
separation of neutral analytes by partition between two
phases. In CEKC, stationary phase is a moving pseudo
stationary phase, however, a fixed stationary phase in
capillary column in case of CEC 82.
v) Micellar electrokinetic capillary chromatography

(MEKC)
In MEKC, the secondary phase is a micellar dispersed
phase in the capillary. The separation principle of MEKC
is based on a differential partition between the micelle
and the solvent and this principle can be employed with
charged or neutral solutes and may involve stationary or
mobile micelles. MEKC has great utility in separating
mixtures that contain both ionic and neutral species, and
has become valuable in the separation of very hydrophobic
pharmaceuticals from their very polar metabolites. In
MEKC, hydrophobic molecules will spend the majority
of their time in the micelle, while hydrophilic molecules
will migrate quicker through the solvent. MEKC utilizes
surfactant above critical micelle concentration as pseudo
stationary phase and can separate neutral as well as
charged analytes as well as separating both charged and
neutral enantiomers with high efficiency, selectivity and
flexibility 94-96. The selectivity of MEKC can be controlled
by the choice of surfactant and also by the addition of
modifiers to the buffer.
Capillary electrochromatography (CEC)

CEC is a separation technique which combines liquid
chromatography and CE. It can be divided into three parts:
i) CEC open-tubular capillary electrochromatography
(OT-CEC) in which the stationary phase is immobilized
on the inner walls of the capillary, ii) CEC with packed
columns, and iii) CEC with monolith 82. The separation
mechanism is a packed column similar to
chromatography. Although CEC and HPLC are very
similar, the main difference is the flat flow velocity profile
generated by the electroosmotic flow in CEC, in
comparison to the pressure driven parabolic flow velocity
profile in HPLC. Using CE capillaries packed with LC
stationary phases, CEC offers the load ability and
selectivity of LC and the high efficiency of CE 83-87. CEC
is used to concentrate samples prior to separation by CZE
MEKC can be employed to separate both charged

and neutral molecules, individually or simultaneously,
including chiral compounds and benefits from high peak
efficiency due to electroosmotic flow in the separation
capillary, compounded with large variety of synthetic
6
separation of various hydrophobic and hydrophilic

compounds, with reduced sample pretreatment steps,
unique selectivities and/or higher efficiencies. Applications
of MEEKC are reported with emphases placed on the
discussion of MEEKC in the separation of chiral
molecules and highly hydrophobic substances, as well as
in the determination of partition coefficients, followed by
a survey of applications of MEEKC in the analysis of
pharmaceuticals and chiral separation110-112. Online
sample concentration, suppressed electroosmosis
MEEKC, chiral separations, MEEKC-MS, MEEKC-ICPMS and ME structure characterisation were also reported
113,114
. MEEKC is used effectively by the pharmaceutical
industry as generic methodology to analyze a broad
spectrum of pharmaceuticals 115 as well as drug partition
in microemulsions 116.
surfactants, organic modifiers, temperature and variable

separation voltage 97. The partial filling micellar
electrokinetic chromatography (PF-MEKC) technique
was reported for comprehensive profiling of metabolites
involved in mammalian steroid metabolism 98 .
Developments in micellar electrokinetic chromatography
(MEKC) have been reported 99,100.
vi) Microemulsion Electrokinetic Chromatography
(MEEKC)
Electrokinetic chromatography is a family of
electrophoresis separation techniques which include
electroosmosis, electrophoresis and chromatography and
the separation is based on a combination of electrophoresis
and interactions of the analytes with additives such as
surfactants that form a dispersed secondary phase moving
at a different velocity 101, also called a pseudo stationary
phase or separation carrier 102-105. A key example of this
was cyclodextrin-mediated electrokinetic chromatography
where the differential interaction of enantiomers with the
cyclodextrins allowed for the separation of chiral
compounds 106,107. This approach to enantiomer analysis
has made significant impact on the pharmaceutical
industrys approach to assessing drugs containing
enantiomers. Methods for correcting enantioselectivities
measurement in the presence of chiral impurities in the
chiral microemulsion were reported 108. The effect of
cosurfactant identity on microemulsion size, elution range,
retention factor, enantioselectivity, methylene selectivity,
efficiency, and resolution in chiral microemulsion
formulations was reported and efficiency and resolution
values varied with different cosurfactants 109.
vii) Capillary isoelectric focusing (CIEF)

CIEF is a separation technique based on isoelectric
point and it relies on a graduated pH buffer gradient to
provide an isoelectric point where the net charge on the
molecule is zero. In CIEF, the molecules migrate under
the influence of the electric field, so long as they are
charged, in a pH gradient generated by ampholytes having
pI values in a wide range (polyaminocarboxylic acids)
and dissolved in the separation buffer 117. CIEF is used
for the separation of amphoteric substances such as
proteins, peptides, amino acids, and pharmaceuticals in
polymer matrices as well as free solutions. CIEF is an
interesting technique for the characterization of
proteins118.
On-line capillary isoelectric focusing-mass
spectrometry (CIEF-MS) enabled determination of
concentrations of peptides and proteins using angiotensin
II and human tetrasialo-transferrin as the model samples.
CIEF-MS employing 1% Pharmalyte 3-10 and a sheath
liquid containing water/methanol/acetic acid (50/49/1)
resolved angiotensin I and II (5 microM each,
DeltapI=0.2) at an Rs value of 2.29. Human tetrasialotransferrin concentration was also determined by CIEFMS 119.
MEEKC is an electrodriven separation technique in

which separations are typically achieved using oil-in-water
microemulsions, which are composed of nanometre-sized
oil droplets suspended in an aqueous buffer. The droplets
are stabilised by a surfactant and a cosurfactant. The
microemulsion droplets are usually formed by sonicating
immicible heptane or octane with water. SDS addition at
relatively high concentrations stabilized the emulsion which
facilitated the separation of both aqueous and waterinsoluble compounds. Compared to MEKC, the presence
of a water-immiscible oil phase in the microemulsion
droplets of MEEKC gives rise to some special properties,
such as enhanced solubilization capacity and enlarged
migration window, which could allow for the improved
Besides performing conventional CIEF, a method

termed as pH gradient driven electrophoresis separated
ampholytic compounds with isoelectric points (pIs) beyond
the pH gradient besides performing conventional CIEF
and the proteins such as lysozyme, cytochrome C, and
7
pepsin with pIs higher than 10 or below 3 were separated

in a pH gradient provided by Pharmalyte (pH 3-10) 120.
CIEF with an open tubular immobilized pH gradient. CIEF
and CZE coupling with LIF detection to create an
ultrasensitive 2-D separation method for proteins were
reported 121. Researchers have reported a multiplexed
capillary electrophoresis system employing an array of
32 capillaries with a micromachined sheath-flow cuvette
as the detection chamber. The sample streams were
simultaneously excited with a 473-nm laser beam, and
the fluorescence emission was imaged on a CCD camera
with a pair of doublet achromat lens. The instrument
produced mass detection limits of 380 +/- 120 yoctomoles
for fluorescein in zone electrophoresis. Capillary isoelectric
focusing of fluorescent standards produced peaks with
an average width of 0.0029 +/- 0.0008 pH. Capillary
coating stability limits the reproducibility of the analysis
122
. Using biologically relevant HIS-tag and FLAG-tag
purifed protein complexes, researchers have demonstrated
the separations of protein complex isoforms of the
mammalian target of rapamycin- complex(mTORC1 and
2) and the subcomplexes and different phosphorylation
states of the Dam 1 complex using native capillary
isoelectric focusing 123.
separation was developed for the separation and

quantitation of alkylamine, antihistamine, dimethindene
and pheniramine enantiomers in various pharmaceutical
preparations such as capsules, oral drops, gel, granulated
powder. The minimal sample pretreatment and low
running costs make the proposed CITP method a good
alternative to commonly used analytical methods (CZE,
HPLC) 129. CITP with conductimetric detection has been
used for separating and determining bopindolol in
commercial mass-produced pharmaceutical preparations
130
.
(ix) Pressurized capillary electrochromatography
(pCEC)
Pressurized capillary electrochromatography (pCEC)
is a separation technology in which the retention
mechanism is based on both chromatographic partition
and electrophoresis. pCEC successfully makes use of
columns with small particles of 1.5m, and dramatically
enhanced the efficiency, speed, peak capacity,
reproducibility and sensitivity, compared to traditional
HPLC and CE. CEC technology is widely applied in
various fields, including pharmaceutical sciences 131,132.
pCEC has several advantages over HPLC: i) high
separation efficiency and resolution using a column packed
with extremely small particles, ii) high selectivity with a
double separation mechanism, iii) high speed with driven
force of both pressure and electroosmotic flow, iv)
quantitative sample injection with rotary type valve, and
v) gradient solvent elution with binary solvent delivery. It
has been widely applied in various fields, including
pharmaceuticals 133,134. A comprehensive survey of
development of CEC and pCEC, including the
development of instrumentation, capillary columns and
stationary phase as well as CEC and pCEC applications
in biotechnology and pharmaceutical analysis were
reported 135.
viii) Capillary Isotachophoresis (CITP)

Capillary isotachophoresis (CITP) is isotachophoresis
performed in a capillary. In CITP, a sample is inserted
between a leading electrolyte and a trailing (or terminating)
electrolyte without electroosmotic flow. The leading
electrolyte has a higher mobility and the trailing electrolyte
has a lower mobility than ions in the sample zone.
Separation in CITP relies on differences in the velocities
of analyte ions within the sample zone 124. CITP is
primarily used as a concentration technique by assembling
specific molecules into small focused zones 125. Cations
and anions cannot be separated at the same time using
CITP. CITP in cationic regime of the separation with
conductometric detection has been used for the separation
and determination of promethazine hydrochloride in
commercial mass-produced pharmaceutical preparations
126
. CITP is an effective way to analyze serum lipoprotein
127
. Determination of neomycin trisulphate in a dosage
form (Neox and Neosol) was carried out by CITP with
conductometric detection 128.
x) Affinity capillary electrophoresis (ACE)

Afnity capillary electrophoresis (ACE) is an
electrophoretic mode that takes advantage of the specic
interactions of receptors, antibodies, or ligands with the
analyte. In contrast to other CE modes, ACE is not
dedicated to general analysis, but rather is focused on
measuring molecular interactions of the solute with
specic receptors 136-138 . This method has been
Cyclodextrin-mediated CITP in cationic regime of the

8
of materials, and the enzymatic reactions for analytical

purposes can be conducted within the capillary.
Furthermore, detection of drugs at low concentration can
be achieved by NCE 154. The analyses of proteins and
nucleic acids at low levels have been described using chipbased nano-liquid chromatography and nano-capillary
electrophoresis in genomics and proteomics 155,156.
successfully used to examine protein-drug, protein-DNA,

peptide-carbohydrate, peptide-peptide/glycopeptide,
DNA-dye, carbohydrate-drug, antigen-antibody, enzymesubstrate, enzyme-inhibitor, and other bimolecular noncovalent interactions 139-142. An experimental design has
been reported for the determination of binding constants
within a couple of hours using capillary arrays or
miniaturized systems 143.
A nanocapillary electrophoretic electrochemical

(Nano-CEEC) chip with amperometric detection for
directly capturing and analysing zeptomole-level (3075
zeptomoles ) detection of catecholamines, including
dopamine and norepinephrine (noradrenaline) that are
released from coupled single PC-12 cells in an integrated
fashion has been developed. This Nano-CEEC chip
integrated a polydimethylsiloxane microchannel for cell
sampling and biomolecule separation and a silicon dioxide
nanochannel for sample pre-concentration and
amperometric detection. The cell-capture voltage ranges
from 0.1 to 1.5 V with a frequency of 110 kHz for PC12 cells, and the single cell-capture efficiency was
optimized by varying the duration of the applied field. All
of the processes, from cell sampling to neurotransmitter
detection were completed within 15 min 157.
Micellar afnity capillary electrophoresis (MACE) is

a fast, manageable, and reliable method for afnity studies
with weak binding ligands. In MACE, the alteration of
the ionic mobility as a factor of the tenside concentration
in the background electrolyte solution is a measure of the
strength of interaction, which may be evaluated graphically
144
. Multiple-injection affinity capillary electrophoresis
(MIACE) is a versatile analytical technique to probe
bimolecular noncovalent interactions and to estimate
binding constants between receptors and ligands.
Scientists demonstrated the use of MIACE and several
variations to MIACE to determine binding constants
between the glycopeptide antibiotics [vancomycin,
ristocetin, and teicoplanin from Streptomyces orientalis,
Nocardia lurida, and Actinoplanes teichomyceticus
respectively] and D-Ala-D-Ala terminus peptides 145.
xiii) Microchip-based capillary electrophoresis

(Microchip-based CE)
xi) Immunoaffinity capillary electrophoresis (IACE)
Microchip-based CE system is one of the techniques

that have been developed in the area of separation on a
microchip 158-161. Analysis of human serum proteins 162,
monoclonal antibodies 163, determination of lactate
dehydrogenase isoenzymes 164 , pharmaceutical
applications and clinical analysis applications were
reported 165,166. A new method to combine chip-PCR
and microchip-based capillary electrophoresis was
developed and reported for detection of SARS virus 167.
IACE combines the advantages of both immunoassay

and capillary electrophoresis, such as high specificity, high
separation efficiency, rapid and low consumption146. IACE
technology is rapidly emerging as the most promising
method for the analysis of low-abundance biomarkers and
involves a three-step procedure: (i) bioselective adsorption
and (ii) subsequent recovery of compounds from an
immobilized affinity ligand followed by (iii) separation of
the enriched compounds 147. IACE has been employed
for the secretion of pro-inflammatory cytokines148 and
for determining protein biomarkers in inflammatory
processes 149.
xiv) Microfluidic capillary electrophoresis (MFCE)

In practice, microfluidic systems are based on the
principles of CE. A universal conductivity detector was
presented that allowed detection of charged species down
to the M level. Additionally, powderblasting was
presented as a novel technique for direct etching of
microfluidic networks. The performance of powderblasted
devices with integrated conductivity detection was
illustrated by the separation of lithium, sodium, and
potassium ions and that of fumaric, malic, and citric acid168.
A microfluidic device was described in which an
xii) Nano capillary electrophoresis (NCE)

NCE is employed especially in proteomics and
genomics and it has gained increasing importance 150-153.
Further, NCE is a suitable technique for samples that may
be difficult to separate by Nano liquid chromatography
as the principles of separation are entirely different.
Moreover, lower detection limits of NCE lead to the
possibility of separating and characterizing small quantities
9
Detection systems
electrospray interface to a mass spectrometer was

integrated with a capillary electrophoresis channel, an
injector and a protein digestion bed on a monolithic
substrate. This chip provided a convenient platform for
automated sample processing in proteomics applications
169
. Microfluidic assays have been developed for three
important drug target classes using the Mobility-Shift
Assay kinetic format on the LC3000 platform. Assay
development and optimization was simplified and
accelerated by the ability to follow the reactions in realtime. Actual Km and Ki measurements were also derived
by the kinetic measurement of initial rates of product
formation, and reaction linearity was directly monitored
170
. A novel MFCE device featuring a double-T-form
injection system and an expansion chamber located at
the inlet of the separation channel utilized a double-L
injection technique and combines the expansion chamber
to minimize the sample leakage effect and to deliver a
high-quality sample plug into the separation channel so
that the detection performance of the device was
enhanced. This MFCE device has demonstrated a sound
potential for future use in high-quality, high-throughput
chemical analysis applications 171.
CE is a growing technique that is continuously

developing with improved detectors 175. Separation by CE
can be detected by several detection devices which include
UV or UV-Vis absorbance, light-emitting diode, laserinduced fluorescence 176, mass spectrometry 177, surface
enhanced Raman spectroscopy (SERS) 178, fluorescence
179
, chemiluminescence 180,181, contactless conductivity
182,183
, amperometry 184-186, radiochemical 187, and NMR
188,189
. A high power UV light-emitting diode for
fluorescence detection in CE separations of proteins, and
peptides, that have been derivatized with UV-excited
fluorogenic labels, e.g., o-phthalic dicarboxaldehyde/betamercaptoethanol has been reported 190. Indirect UV
detection is widely used for detecting solutes having no
chromophores such as metal ions or inorganic anions, for
example chloride, sulphate and nitrate 191. This type of
determination is popular in the water and pharmaceutical
industries. Low UV wavelengths (ca 190-200 nm) are
also used to detect simple compounds such as organic
acids 192.
A simultaneous LIF, coaxial thermal lens spectroscopy
(TLS) and retro-reflected beam interference detection
for CE, has been described. In its optical scheme, a diodepump solid-state (DPSS) laser was employed as the pump
laser in both LIF detection and coaxial TLS detection,
and a He-Ne laser was utilized as the probe laser in coaxial
TLS detection and RBI detection. LIF and coaxial TLS
detection owned high sensitivity, and retro-reflected beam
interference detection indicated versatile property, based
on which the reported detection achieved a sensitive and
universal detection for CE 193. Microchip microemulsion
electrokinetic chromatography with indirect fluorimetric
detection provided an accurate method for estimating log
P octanol/water values for neutral and basic compounds
and also a means for analyzing compounds that are nonfluorescent 194. Microchip capillary electrophoresis,
coupled with indirect fluorescence detection was
investigated for estimating the pK(a) values of nonfluorescent compounds including several of
pharmaceutical importance with pK(a) values from 10.3
to 4.6 195. The different approaches for constructing
carbon nanotubes, nanoparticles, and nanorods-based
detectors for conventional CE and microchip
electrophoresis have been reported. In this context, the
A fabrication process for producing monolithic

sampling probes on glass chips, with tip diameters of a
few hundred micrometers was developed, using simple
tools including a glass cutter and a bench drill. Microfluidic
chips with probes fabricated by this approach were
coupled to a linearly moving slotted-vial array sample
presentation system for performing continuous sample
introduction in the chip-based CE system. The
performance of the system was demonstrated in the
separation of fluorescein isothiocyanate-labeled amino
acids with LIF detection, by continuously introducing a
train of different samples without interruption 172. A chiral
separation model of gel electrochromatography in a
polydimethylsiloxane microfluidic device for amino acids
has been reported. In this context, six pairs of fluorescein
isothiocyanate-labeled dansyl amino acids were separated
in a 36-mm effectual separation channel in less than 120
sec 173. A simple, rapid MFCE system with a continuous
sample introduction interface has been described for
analysis of two commercial pharmaceutical preparations
containing trimethoprim, sulfadiazine, and
sulfamethoxazole with UV detection at 214 nm174.
10
MS) interface utilizing a flow-through microvial is used

to ensure the electric continuity and supply the catholyte
and mobilizer solutions during the CIEF and mobilization
process. The flow-through microvial provided a stable
chemical environment and improved the ionization
efficiency without significantly diluting the analyte. The
CE-MS interface facilitated the transfer of the mobilized
CIEF effluent to the site of electrospray ionization, and
the gaseous ions can be detected directly by a mass
spectrometer. It also allows for complete focusing and
mobilization processes to be performed automatically in
programmed sequences with commercial CE systems.
Two different strategies, using either a part of the capillary
or the flow-through microvial of the CE-MS interface as
the catholyte reservoir for bare fused silica capillaries or
neutral coated capillaries, respectively, were developed
for automated CIEF-electrospray ionization (ESI)-MS.
Reasonable separation efficiency was achieved using
proper concentration of carrier ampholytes and suitable
strategies of electroosmotic/electrophoretic mobilization
207
.
enhanced detection performance of nanomaterial-based

detectors, such as higher sensitivity, improved limits of
detection, and higher peak capacity, along with various
biomedical applications were described 196.
Hyphenated capilliary electrphoresis techniques
The combination of the powerful technique of mass
spectrometry (MS) with CE was first reported by
Olivares et al.197, Smith et al.198 and Chamberlain 199.
CE-ESI-MS represents a promising hyphenated
microseparation platform in metabolomics and offers a
convenient format for the separation of complex mixtures
of cationic, anionic, and/or zwitterionic metabolites, as well
as their isobaric/isomeric ions without complicated sample
handling 200. The CE coupling to sensitive and selective
MS detection allows the qualitative and quantitative
analysis of even complex samples. Inductively coupled
plasma mass spectrometry (ICP-MS) and electrospray
ionization time-of-flight mass spectrometry (ESI-ToF-MS)
coupled to CE are complementary tools that are used in
the field of speciation. Structural information can be
obtained by means of ESI-ToF-MS, while ICP-MS is
ideally suited to quantify elements even in very low
concentration ranges 201. The complementary application
of CE-ICP-MS and CE-ESI-MS detection techniques to
the structural and functional characterisation of metalbinding proteins and their structural metal-binding moieties
was reported 202. The instrumentation and the integration
of mass spectroscopy and CE for the analysis of small
oligonucleotides and DNA-ligand interactions have been
reported 203,204.
A highly efficient and reliable membrane-assisted

capillary isoelectric focusing (MA-CIEF) system coupled
with MALDI-FTMS for the analysis of complex
neuropeptide mixtures was reported. The new interface
consisted of two membrane-coated joints made near each
end of the capillary for applying high voltage, while the
capillary ends were placed in the two reservoirs which
were filled with anolyte (acid) and catholyte (base) to
provide pH difference. Optimizations of CIEF conditions
and comparison with conventional CIEF were carried out
by using bovine serum albumin (BSA) tryptic peptides. It
was shown that the MA-CIEF could provide more
efficient, reliable and faster separation with improved
sequence coverage when coupled to MALDI-FTMS.
Analyses of orcokinin family neuropeptides from crabs
Cancer borealis and Callinectes sapidus brain extracts
have been conducted using the established MA-CIEF/
MALDI-FTMS platform. Increased number of
neuropeptides was observed with significantly enhanced
MS signal in comparison with direct analysis by MALDIFTMS. The results highlighted the potential of MA-CIEF
as an efficient fractionation tool for coupling to MALDI
MS for neuropeptide analysis 208.
A growing number of CE-MS applications make use

of capillaries where the internal wall is modified with
surface coating agents. In CE-MS, capillary coatings are
used to prevent analyte adsorption and to provide
appropriate conditions for CE-MS interfacing. In CE-MS,
separation is achieved through channels etched on the
surface of the capillary (connected to an external highvoltage power supply) which delivers sample to ESIMS. It is an automatable approach, with great sensitivity.
An overview of the various capillary coating strategies
used in CE-MS was reported 205. MEKC coupled to
ESI-MS method shows good potential for the detection
and structure elucidation of minor impurities in drug
substances 206.
An orthogonal method of coupling MEKC and MS

utilized atmospheric pressure chemical ionization (APCI)
A capillary electrophoresis mass spectrometry (CE11
CE applications in pharmaceutical analysis
and atmospheric pressure photoionization (APPI) 209. In

these methods the ionization efficiency has been shown
to be unaffected by the surfactant SDS using both APCI
and APPI 210,211. The APCI-MS set-up enabled detection
of basic, neutral, and acidic compounds, whereas apolar
and ionic compounds could not be detected. The analysis
of a mixture of basic compounds and a steroid using
volatile and nonvolatile background electrolyte further
demonstrated the feasibility of CE-APCIMS 212. The
successful coupling of CZE, NACE, MEKC and CEC
with MS detection provided an efficient and sensitive
analytical tool for the separation, quantitation, and
identification of numerous pharmaceutical and therapeutic
compounds. Chip-based microdevices were also reported
regarding fabrication methods, designs and MS interfacing
213
. A microchip-based capillary electrophoresis system
was interfaced with a microwave induced plasma optical
emission spectrometry (MIP-OES) to provide copper
species separation capabilities 214 . The use of
nanoparticles as pseudostationary phasess, in combination
with continuous full filling (CFF) and an orthogonal ESIinterface, has shown to be a good way to separate neutral
analytes without affecting the electrospray process or
contaminate the ion source 215,216.
CE is a powerful analytical technique which is

increasing in utility in the pharmaceutical industry. It is
used as an alternative or complementary technique to
HPLC due to its high efficiency, speed of analysis,
reduction in solvent and sample consumption, and low
operating cost compared to HPLC methodology 224. CE
is used for routine, particularly for analyzing serum
proteins and disease markers in many hospitals and clinics.
CE technique has also dramatically increased throughput
for DNA profiling in criminal investigations and CE data
have been shown to be credible evidence in law courts,
and forensic testing laboratories have published validated
procedures. Pharmaceutical companies make extensive
use of CE, in particular for chiral separations, and the
technique is widely accepted by regulatory authorities such
as the US Food and Drug Administration. CE has been
widely adopted for analyzing biomolecules such as DNA
and proteins by CE gel, steroids by MECC 225.
Applications of CE, CEC and their derived techniques
to assay active pharmaceutical ingredients (APIs), drug
impurity testing, chiral drug separation, determination of
APIs in biological fluids 226-235 and therapeutic drug
monitoring have been reported 236,237. CE has contributed
immensely to better understanding of affinity interactions
between cyclodextrins and chiral drugs 238. CE methods
were reported for assessing drug stability, separating
metallodrugs and their metabolites, characterizing related
metal-bioligand species, metabolomic and proteomic
analysis focussed on metal-based drugs 239.
The improvements in the separation as well as the

coupling of CE with MS have been reported 217-220.
Reproducible investigations of the interaction between a
novel Ru-based anticancer agent indazolium [transtetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) with
the proteins (human serum albumin (HSA) and transferrin
) as well with human plasma, human serum and HSAand IgG-depleted human serum was reported to shed light
on the fate of the drug upon intravenous application 221.
The
coupling
of
Ru(bpy) 3 2+ -based
electrochemiluminescence detection with CE was
reported for the simultaneous determination of proline
(association with chronic uremia ) and pipemidic acid (used
in the treatment of Gram-negative urinary tract infections
) in human urine 222. A pCEC coupled with on-column
chemiluminescence detection was reported for direct
determination of amino acids, which was based on the
principle of an enhanced effect of Cu(II)amino acid
complexes on the chemiluminescence reaction between
luminol and hydrogen peroxide in alkaline solution 223.
CE assay was developed for the stability evaluation

of tramadol enantiomers in commercial tablets using
maltodextrin as chiral selector and best separation for
the tramadol enantiomers was achieved on an uncoated
fused-silica capillary at 20C using borate buffer (50
mM, pH 10.2) containing 10% m/v maltodextrin and using
UV detector at 214 nm. The range of quantitation for
both enantiomers was 5100 g/mL (R>0.996) 240.
Examples of mechanistic aspects of capillary
electromigration enantioseparations and applications of
chiral pharmaceutical and biomedical analysis were
reported 241. CE applicability to the routine quality control
was successfully demonstrated for the determination of
bromhexine and amoxicillin, and pyrimethamine and
12
sulfadoxine in several pharmaceutical formulations 242,243.

The pharmaceutical analysis applications used for various
modes of capillary electrophoresis have been reported
244-248
. CE is commonly used in the analysis of small
molecules 249. Proteomic analysis with CE-MS coupling
permits fast and accurate identification and differentiation
of polypeptide patterns in the urine of patients with IgA
nephropathy, allowing differentiation from healthy controls
and, probably, other renal diseases 250. CZE was used for
the analysis of water-soluble vitamins in corns, in which
on-line concentration methods, namely field-enhanced
sample stacking and dynamic pH junction, were utilized
to improve the detection sensitivity 251.
attenuated total internal reflectance infrared

microspectroscopy (FT-IR) 261. Some applications of
CEC in the analysis of pharmaceuticals products have
been reported 262-265.
The mixed buffer of 20 mM phosphate/10 mM citrate
containing 5 mM methyl-!-cyclodextrin or 5 mM
carboxymethyl-!-cyclodextrin as a chiral selector showed
superior separation ability compared with single component
buffers in CE separation of sibutramine enantiomers. This
method was applied successfully to the enantiomeric
determination of (R)- and (S)-sibutramine in commercial
pharmaceutical formulations. Further, the resolution of the
sibutramine enantiomers was attributable mainly to the
difference in stability constants 266. A simple method based
on capillary electrophoresis with a capacitively coupled
contactless conductivity detector (CE-C4D) was found
suitable for controlling pharmaceutical formulations
containing suxamethonium and degradation products 267.
Since different drug metabolite enantiomers are

formed in many metabolic pathways, the advantage of
CE over HPLC is considered better for chiral separation
without the need of special expensive columns. The
sample preparation, separation and detection modes
involved in CE drug metabolism studies, and distinction
between drug metabolism analysis in vivo and in vitro
has been reported 252. In pharmaceutical industry, CE has
been used to support all of stages from chemical synthesis
to compound selection for drug development and quality
control. In this context, various applications include:
physicochemical profiling; pKa screening, Log p screening,
enzyme activity screening, chiral discovery and screening,
metabolomics, immunoassay, SDS-protein sizing,
oligonucleotide quality control, genetic analysis,
quantitation of gene expression, viral load quantitation,
genotyping, automated DNA sequencing and DNAprotein interactions 253. Recently, researchers have
developed a CZE method of analysing antimalarial drugs
based on sulfadoxine and pyrimethamine and analysis of
different tablet formulations has shown a good agreement
with the liquid chromatography method described in the
United States Pharmacopoeia 254.
The affinity of drugs to both to excipients and to

vehicle systems is of utmost importance in the
development and optimizations of pharmaceutical
formulations. ACE finds application for characterization
of ion pairing of hydrophilic drug with lipophilic counter
ions. Results showed that lipophilic counter ions as
absorption enhancer via ion pairing improved the oral
bioavailability of hydrophilic drugs such as cefpirome. In
addition, ACE was used to optimize the solubilization
capacity for lipophilic drugs of colloidal formulations such
as mixed micelles and microemulsions. Furthermore, ACE
was applied to determine the potential toxic labile iron in
parenteral iron formulations using off-capillary and on
capillary complexation with EDTA 268.
The results obtained with the PEGylated liposomes
demonstrated that CE as a useful tool for the
characterization of liposomal drug formulations such as
oxaliplatin (anti-cancer agent) 269. A method based on
CE-ICP-MS and interface units, was developed for
ascertaining possible metabolic transformations of metalbased drugs. In this context, using a novel anticancer
gallium compound, it was demonstrated that the drug
remains intact in the simulated intestine juice. On the
contrary, it undergoes a marked change in speciation
(mostly, due to binding to transferrin) in human serum 270.
The copper (II) complex of a modified cyclodextrin,
namely 6-mono-deoxy-6-[4-(2-aminoethyl) imidazolyl]-!-
Due to inexpensive quality control as well as projecting

CE as a powerful alternative to HPLC, CE approach has
been progressively introduced in the pharmaceutical
industry 255-258. CE has been used in the analysis and
small-scale separation of PEGylated proteins 259. The
CZE method for the simultaneous analysis of omeprazole
and lansoprazole was achieved and this method was
applied to determine the quality of commercial capsules
260
. Suxamethonium was determined by CE coupled with
13
anticancer drug (oxaliplatin) with human serum albumin

(HSA) in aqueous solution at physiological pH with drug
concentrations of 10 to 100 microM and a constant
concentration of HSA (5.0 x 10-5M) were studied using
CIEF with whole column imaging detection. The altered
CIEF profile demonstrated the possible conformation
change due to the binding of the drug. Further, a significant
proteins pI shift for higher HSA-oxaliplatin incubation
ratios was observed. Furthermore, spectroscopic evidence
showed that oxaliplatin caused the fluorescence quenching
of HSA by formation of HSA-oxaliplatin complex. In
addition, the quenching rate constants K(q) at three
different temperatures indicated the presence of static
quenching mechanism in the interactions of oxaliplatin with
HSA 280.
CD was investigated in ligand exchange capillary

electrophoresis (LECE) using ESI-MS as the detection
device. This hyphenated method potential was compared
with the results previously obtained with optical detection
by studying the chiral resolution of tryptophan racemate.
It was observed that chiral separation conditions
compatible with LECE-ESI-MS could be achieved based
on the figures of merit obtained by LECE-UV. The values
of detection limit obtained by LECE-ESI-MS were
significantly better than those obtained by LECE-UV 271.
Various CE modes were applied to different areas of
pharmaceutical analysis such as enantiomer separation,
analysis of small molecules such as amino acids or drug
counter-ions, pharmaceutical assay and physiochemical
measurements such as log P and pKa of compounds 272275
.
A simple ampholyte-free CIEF free-flow

electrophoresis design establishing a pH gradient spanning
from 2.3 to 8.9 was reported and the separation of proteins
such as !-Lactoglobulin, Hemoglobin, Myoglobin and
Cytochrome C was confirmed by CIEF with pI markers
281
. CIEF has been proved as a high-resolution technique
for protein and peptide separation in pharmaceutical
industries for the analysis and characterization of, for
example, isoforms of glycoproteins, point mutations in
hemoglobin, and peptide mapping. Further, hyphenation
to MS and chip based CIEF (microfabrication) have
shown promise and CIEF kits and specific recipes /
application notes are available from vendors of CE
equipment, as are a vast amount of publications and
handbooks of CE published over recent years 282.
In order to automate the key tasks in large-scale

nucleic acid CE analysis (including the profile alignment),
researchers reported a computational method called highthroughput robust analysis for capillary electrophoresis
(HiTRACE). In this context, HiTRACE quantitation of
the largest datasets was achieved in 312 min as compared
to 710 h of manual intervention using prior approaches
276
. An automated CZE system utilizing a capillary
cartridge having a plurality of capillary tubes was reported
277
.
Macrocyclic antibiotics (ansamycins and the
glycopeptides) and macrolides are used as chiral selectors
in CE for enantioseparation applications. Clarithromycin
lactobionate, belonging to the group of macrolide
antibiotics, allowed excellent separation of the enantiomers
of metoprolol, atenolol, propranolol, bisoprolol, esmolol,
ritodrine, and amlodipine, as well as partial
enantioresolution of labetalol and nefopam at the buffer
pH range of 7.37.5 using 12.5 mM borax buffer with
50% v/v methanol, 60 mM clarithromycin lactobionate,
and 20 kV applied voltage278. Chiral CE helps better
understanding of mechanisms of enantioselective
intermolecular interactions, and the examples include chiral
pharmaceuticals in bulk and formulations in presence of
(sometimes also achiral) impurities, chiral drugs with
multiple centres of chirality, chiral drugs and metabolites
in complex biomedical matrices such as urine, plasma,
etc 279.
The results of a CE microfluidic device with a novel

injection structure with a 45 U-shaped injector and an
expansion chamber at the inlet of the separation channel
significantly prevented sample leakage and transports
suitable sample plugs into the separation channel enhancing
the detection performance 283. The development and
application of the electrophoretic and microchip
technologies for the analysis of outer membrane protein
was reported 284,285. Pharmaceutical analysis focused
on the detection of anions and cations in the course of
stoichiometric analysis was achieved by various CE
techniques 286. CE-MS was applied to the chiral
separation of baclofen using sulfobutylether-!-cyclodextrin
chiral selector in partial filling counter current mode, and
on-line UV detection was simultaneously used. The
Drug-protein interactions between the platinum-based

14
improvements for enhancing sensitivity in chiral analysis

by CE were reported 293. Off-line and on-line sample
treatment techniques, on-line sample preconcentration
strategies based on electrophoretic and chromatographic
principles, and alternative detection systems to the widely
employed UV/Vis detection in CE are the most relevant
approaches discussed for improving sensitivity. Microchip
technologies can open up great possibilities to achieve
sensitive and fast enantiomeric separations 294. Sulfated
cyclodextrins (HS-CDs) were used as selectors for chiral
resolution of seven basic and two zwitterionic drugs. The
electrophoretic conditions for the stereoselective analysis
of drugs were in the carrier mode with 25 mM sodium
phosphate buffer containing 1.25% w/v of each HS-CD
at pH 2.5 with an applied voltage of +15 kV and rapid
enantioresolution of all drugs were achieved under these
conditions 295.
cyclodextrin showed stereoselective complexation

towards baclofen enantiomers, thereby, allowing chiral
resolution at low concentration. Complete enantiomeric
separation was obtained by using 0.25 M formic acid
background electrolyte containing 1.75 mM of chiral
selector and water/methanol (30:70, v/v) 3% formic acid
as sheath liquid 287. The separation and determination of
amoxicillin, ampicillin, sulfamethoxazole, and
sulfacetamide was achieved by MEKC method using UV
detection at 210 nm 288. Stereoselective methods
employing capillary electrophoresis for chiral drug
metabolism studies were also reported 289.
MEKC method with diode-array detection for the
simultaneous and short-time analysis of six statin drugs
(lovastatin, simvastatin, pravastatin, fluvastatin,
atorvastatin and rosuvastatin) in pharmaceutical samples
was reported using ketoprofen as an internal standard.
Optimized conditions were found to be a 25 mM borate
buffer pH 9.5 with 25 mM sodium dodecyl sulphate and
10% methanol added as an organic modifier, an applied
voltage of 23 kV and a separation temperature of 30 C.
The linearity of the detector response for each statin was
within the concentration range from 10 to 100 g mL1
with a correlation coefficient greater than 0.9994 290.
A bromoacetate-substituted !-cyclodextrin
(Br-!-CD) was successfully bound to the 3aminopropylmethyldimethoxysilane-modified capillary
column prepared by microwave irradiation, as a chiral
stationary phase for open tubular capillary
electrochromatography. Compared with conventional
synthesis, the microwave-assisted process significantly
decreased the preparation time of the stationary phase
from 16 h to 40 min. Baseline chiral separation of 1phenyl-1,2-ethanediol was achieved using the Br-!-CD
modified column 296. The applications of CE and
microchip CE with conductivity detector C 4 D in
pharmaceutical and biological analysis have been reported
297
. CZE with a capacitively coupled contactless
conductivity detector (CE-C4D) was successfully applied
to the simultaneous determination of atenolol and amiloride
in different pharmaceutical tablet formulations 298.
Determination of ethambutol , a first-line drug against
tuberculosis, was achieved using CE based method with
capacitively coupled contactless conductivity detection
299
. The determination of ciclopirox olamine in
pharmaceutical formulations using CE with capacitively
coupled contactless conductivity detection was reported
in an alkaline and acidic medium. A linear working range
from 2.64 to 264 g/mL in sodium hydroxide electrolyte as
well as low detection limit (0.39 g/mL) and a good
repeatability (RSD = 3.4% for 264 g/mL ciclopirox solution
(n = 10)) were achieved. Olamine was determined in its
cationic form when acetic acid was used as the electrolyte
MEEKC method has been developed which

separated a range of nine steroids and was validated for
the determination of 17-estradiol content, a hormone
steroid, in transdermal patches. A microemulsion containing
ethyl acetate, butan-1-ol, sodium dodecyl sulfate, 15%
(v/v) acetonitrile and 12 mmol L1 sodium tetraborate
aqueous buffer at pH 9.2 was used with direct UV
detection at 200 nm. The method was validated for the
determination of 17-estradiol content, a hormone steroid,
in transdermal patches 291.
A chiral microemulsion electrokinetic chromatography
method has been developed for the separation of the
enantiomers of the phenethylamines ephedrine, Nmethylephedrine, norephedrine, pseudoephedrine,
adrenaline (epinephrine), 2-amino-1-phenylethanol,
diethylnorephedrine, and 2-(dibutylamino)-1-phenyl-1propanol, respectively. Additionally, the developed method
was successfully applied to the related substances analysis
of noradrenaline, adrenaline, dipivefrine, ephedrine and
pseudoephedrine monographed in the European
Pharmacopoeia 292. The methodological and instrumental
15
nevirapine (mixture A) and zidovudine/didanosine/ritonavir

(mixture B) were quantitated in human serum samples
314-316
. Researchers demonstrated the potential of CE as
a routine analytical separation technique for the analysis
of non chiral, chiral and impurities in pharmaceuticals
formulation of fluoroquinolones and primaquine 317. A
sweeping CE was established for the determination trace
levels of abused drugs in addicts urine 318. The analysis
of anxiolytic drugs, including barbiturates and
benzodiazepines, by CE with bare and coated capillaries
was also reported 319,320. The determination of hydroxybutyric acid in urine and serum samples with (CEC4D was reported 321. MEKC analysis of a group of
date-rape drugs by permitted the analysis of uncharged
molecules by providing a secondary separation through
the addition of a surfactant that formed into micelles 322.
solution. The results obtained include a linear range from

26.4 to 184.8 g/mL and a detection limit of 2.6 g/mL
olamine 300.
Micro-electrodialysis and CE were combined for rapid
pretreatment and subsequent determination of inorganic
cations in biological samples as such, and this hyphenation
method greatly improved the analytical performance of
the latter as the adsorption of high molecular weight
compounds present in real samples on the inner capillary
wall was eliminated 301. CE and CE-based analytical
tools have great potential in the determination of lipids 302
and were employed to study interactions between analytes
and biomimetic lipid vesicles 303.
Most NACE applications carried out for the analysis
of compounds of pharmaceutical interest include (i)
analysis of drugs and related substances, (ii) analysis of
chiral substances, (iii) analysis of phytochemical extracts
and (iv) analysis of drugs in biological fluids 304.
Researchers reported the ingredients in acne formulations
(salicylic acid, cloramphenicol and resorcinol in presence
of azulene) by CZE 305. CE has been used for analysis of
various classes of antifungal compounds such as
miconazole and 5-fluorocytosine 306. Developments in
chiral separation using CZE, EKC, and CEC were
reported 307. Researchers have reported on a novel closedloop system to identify ionic species with similar
electrophoretic mobilities unlike many conventional CE
systems. In this method, the sample undergoes separation
to travel back and forth along the short channel multiple
times, and moreover, it was independent of migration time
308
. MEKC has been used for analysis of water-soluble
neutral compounds, weak acids and bases 309,310.
ACE found applications in the identification of

antimicrobial compounds that bound the novel target YihA
[an essential gene of unknown function in both
Escherichia coli and Bacillus subtilis conserved in
bacteria and represents an attractive target for the
discovery of new antibiotics]. YihA encoded a putative
GTP-binding protein and screened a small-molecule library
of 44,000 compounds initially identified 115 binders, of
which 76% were confirmed. Furthermore, the ACE assay
distinguished diverse compounds that possessed drug-like
properties and antimicrobial activity against drug-resistant
clinical isolates. Such data validated ACE as a valuable
tool for the fast, efficient detection of specific binding
molecules that possess biological activity 323.
Researchers have demonstrated development of
electrophoretically mediated micro analysis for screening
protein tyrosine phosphatase inhibitors in natural extracts
324,325
. The determination of the physicochemical and
thermodynamic parameters of drug compounds offering
strategies to explore and characterize interactions between
drugs, drug vehicles, and biological membranes to facilitate
developments in controlled drug delivery was achieved
using ACE 326.
A simple, rapid microfluidic capillary electrophoresis

system with a continuous sample introduction interface
has been applied to the analysis of two commercial
pharmaceutical preparations containing trimethoprim,
sulfadiazine, and sulfamthoxazole with UV detection at
214 nm, achieving baseline separation within 2.5 min 311.
CE significance as a complementary biophysical tool for
protein characterization has been reported 312. Lamivudine,
didanosine, and saquinavir were simultaneously
determined by CZE 313 . MEKC was used for
determination of stavudine, didanosine, saquinavir (mixture
A) and stavudine, didanosine, efavirenz (mixture B), the
anti-HIV drug mixtures containing zidovudine /didanosine/
Regulatory requirements limit the amount of the host

cell DNA that can be present in vaccines or human
therapeutics. The viral quantitative capillary
electrophoresis was successfully applied to quantify the
oncolytic vaccinia virus in the range of 106 to 1012 ivp/
mL. In this context, researchers separated intact virus
16
particles and the residual DNA, and measured the level

of virus contamination with DNA impurities using CE
method, and intercalating YOYO-1 dye was used to detect
the encapsulated and free DNA by laser-induced
fluorescence 327. Applications of capillary electrophoresis
with capacitively coupled contactless conductivity
detection (CE-C4D) in pharmaceutical and biological
analysis were reported 328.
and protein mapping. Separation effectiveness of this 2D system was demonstrated by the analysis of tryptic
digest of BSA and human red blood cell lysate. A
theoretical peak capacity of approximately 24 000
achieved for bovine serum albumin digest proved its
promising potential for the application in proteomics 337.
DNA fragments, SDS protein and macromolecules
analysis has been achieved using CGE 338-342.
CE application in biopharmaceutical analysis
Flow Induced Dispersion Analysis (FIDA), a general

methodology for assessing non-covalent interactions, has
been used on small molecules, proteins (such as antibodies)
and DNA 343. The application of CE to the glycoform
analysis of glycoproteins and profiling of the N-linked
glycans released from glycoprotein pharmaceuticals, and
applications for structural analysis using CE-MS technique
and glycan profil1ing method for therapeutic antibody were
reported 344.
CE has demonstrated to be a complementary

alternative to chromatographic techniques in
biopharmaceutical analysis. The complete
characterization of biopharmaceutical drugs such as
erythropoietin and various therapeutic monoclonal
antibodies for glycosylation compositions, IgG purity, and
impurities for quality control purposes are of utmost
importance. Further, therapeutic biomolecules have a
highly complex composition and structure. Moreover, the
products may vary in structure due to the complexity of
cell culture and purification processes 329. Various modes
of CE offer several possibilities for biopharmaceutical
analysis including glycosylated therapeutic proteins,
monoclonal antibodies, pharmaceutical and
biopharmaceutical impurities 330. CZE has been used for
proteins as long as there are differences in charge:frictional
drag ratios 331. The acceleration and rapid success of
Human Genome Project was possible due only to the
introduction of CE-based sequencers 332. CE-SDS gel
application has become the gold standard for protein purity
and heterogeneity analysis in biopharmaceutical
laboratories and several major biopharmaceutical
companies have adopted CE-SDS as a replacement to
SDS-PAGE. Denatured proteins can be reduced or left
intact for separation and subsequent analysis 333. Various
modes of CE offer numerous possibilities for
biopharmaceutical analysis 334. CE- laser-induced
fluorescence detection method has been useful for both
structural characterization and quantitative profiling of Nlinked oligosaccharides derived from recombinant
monoclonal antibodies pharmaceuticals 335.
Researchers have developed a procedure for the

removal of polysorbate 80 from formulated epoetin alfa,
allowing the material to be analyzed by European
Pharmacopoeia CZE modified method 345. Practical
aspects of CE devoted to proteins, peptides, and techniques
especially useful in the area of recombinant DNA products
346
, analyses of dosage forms of biotechnology derived
proteins of pharmaceutical importance as well as the
identification and examination of the peptides, obtained
after enzymatic cleavage of proteins by CE have been
reported 347. CE has been used in the analyses of
Escherichia coli-derived proteins, glycosylated proteins
derived from mammalian cell cultures, carbohydrate
chains enzymatically removed from the protein, analysis
of the antisense oligonucleotides for the determination of
purity and the analytical studies on the metabolism of these
modified oligonucleotides 348.
A major advance for CE is its recognition by various
regulatory authorities. A general monograph on CE is now
included in the United States Pharmacopoeia (USP, which
has also been published in the European Pharmacopoeia
(EP) and Japanese Pharmacopoeia 349. CE methods have
emerged in the official Pharmacopoeial texts. The ICH
Steering Committee, based on the evaluation by the Q4B
Expert Working Group (EWG), recommended that the
analytical procedures described in the official
Pharmacopoeial texts, Ph. Eur. 2.2.47. Capillary
CIEF applications related to analysis of

biopharmaceutical compounds and isolated proteins for
metabolomic studies have been reported 336. A novel online 2-D system combining CIEF with pCEC using a microinjection valve as the interface was developed for peptide
17
powerful data processing capabilities of Agilent

MassHunter and BioConfirm software, enabled
identification of the glycopeptides and glycan moiety
attached to the complex protein. The combination of CE
with Q-TOF MS has proved a valuable tool for peptide
mapping of small quantity biopharmaceuticals 359. The
potential of ligand-exchange capillary electrophoresis
method in solving major problems, such as the separation
of enantiomers and the determination of biologically active
compounds poorly absorbing in the UV region (sugars,
amines, and amino acids) were reported 360.
Electrophoresis, JP General Information 4. Capillary

Electrophoresis, and USP General Information Chapter
<1053> Biotechnology-derived Articles Capillary
Electrophoresis,4 can be used as interchangeable in the
ICH regions.
The key features for method validation of small
molecules using CE in the context of the pharmaceutical
industry have been reported 351,352. The determination of
Kd of three drugs namely daunorubicin, pharmorubicin
and idarubicin was reported using CZE with amperometric
detection and the pKa values obtained through the method
were in agreement with the values by typical
spectrophotometric method 353. A CZE with amperometric
detection method has been developed for the determination
of idarubicin in human urine 354, and also for the separation
and determination of sucrose, glucose, and fructose in
Chinese traditional drugs, namely Astragalus
Membranceus (Fish.) Bge, Angelica and Codonopsis
pilosula (Franch.) Nannf 355. The analysis of doxorubicin
(DOX) and daunorubicin (DAU) in human serum using
CZE and mirochip-based CE-LIF detection was validated
with regard to reproducibilities, linearity and limit of
detection. The optimum electrophoretic separation
conditions were 10 mM sodium tetraborate buffer at pH
9.5 with 40% acetonitrile (V/V) and a separation voltage
of 2.1 kV. DOX and DAU were separated in 60 s under
the optimum separation conditions. Linear relationships
were obtained between the concentration and peak area
in the 175 g mL-1 range and with the detection limits of
0.3 and 0.2 g mL-1 for DOX and DAU, respectively
356,357
. Researchers have reported advances in CE theory,
instrumentation, and methodologies that are specific to
nucleic acids, proteins and peptides, carbohydrates, lipids,
single cells, and bioparticles, as well as advances in the
use of CE to define functional assays or to investigate
biomolecular interactions 358.
CE applications in biotechnology
CE separation technique is broadly used in the
biotechnology industry for carbohydrate analysis and
significant improvements for the standard CE sample
preparation method of glycan analysis of glycoproteins
by CE-LIF and CE-MS were reported 361-366.
AdvanCE FS platform provided rapid separation
and ample resolution with excellent sensitivity and dynamic
range, to benefit a variety of applications in genomic
research 367. Several glycoproteins such as fetuin, alpha1
acid glycoprotein, IgG, and transferrin separation was
achieved within only 5 h with the three-step procedure
involving release of glycans, derivatization with Fmoc, and
CE-ESI MS analysis. This method was also applicable
for the analysis of N-glycans derived from monoclonal
antibody pharmaceuticals, as well as from alphafetoprotein (one of the tumor markers of hepatocellular
carcinomas) 368. Reports on pharmaceuticals and
biotechnology products analyses by CEC were compiled
369
. A number of collaborations between various
pharmaceutical companies and regulatory authorities for
the analysis of biomolecules using CE demonstrated the
robustness of CE-SDS across eight different organisations
370
. CE found applications for the separation of
microorganisms as well as the detection and isolation of
Candida albicans fungus in human blood 371. The
applications of microchip-based CE to the detection and
separation of DNA fragments in biotechnological and
clinical research were reported 372.
The applicability of CE-MS was demonstrated on a

separation of glycopeptides from monoclonal antibodies
(mAb) and to identify the glycan modifications. The tryptic
peptide map of the mAb was generated and the
glycopeptide was assigned using accurate mass
measurement. Subsequently, BioConfirm software was
used to map the glycosylation site on the mAb. The
extremely efficient CE separation and superior mass
accuracy of the Q-TOF platform, combined with the
CE methods showed promise for analysis of

resveratrol and other flavonoid antioxidants (glycosides
and aglycones) in wine 373. A CE-MS technique has been
developed for age estimation of silk textiles based on amino
18
fluorescence detection
acid racemization rates ranging in age from several

decades to a few-thousand-years-old. The analysis takes
20 min, consumes only nanoliters of the amino acid
mixture, and provided both amino acid composition profiles
and d/l ratios for 11 amino acids 374. Lysozyme, bovine
serum albumin and beta-galactosidase were successfully
separated rapidly using a laboratory-made miniaturized
capillary electrophoresis apparatus provided with a
confocal fluorescence spectrometry 375.
389
Inorganic nanoparticles assisted CE pharmaceutical

applications
CE has seen used in the separation and
characterization of inorganic nanoparticles (Ag, Au, TiO2,
Al 2 O 3 , Fe 2 O 3 ) 390-394 , quantum dots(QD) 395 , QDconjugates with bovine serum albumin and horse radish
peroxidase 396, and QD-conjugates with Ulex europaeus
and anti-von Willebrand factor 397. The immunoassay
application of QD in CE offers considerable advantages.
In this context, quantum dots were conjugated with
antibody and subsequently tested by electrophoretic
separation of free antibody and antibody-antigen complex.
It was observed that antibody was fluorescently labelled
by quantum dots via conjugation procedures and its
electrophoretic characteristics were effectively modified
due to the attachment of quantum dots. The determination
of human IgM by direct CE based immunoassay could
be easily achieved by simply changing the pH value of
separation buffer. Further, satisfactory separation of
complex from free antibody could be achieved with 20
mM sodium tetraborate as separation buffer, at pH 9.8
398
. CE has also been used for immunoassays involving
hepatitis B, prion protein, alpha-fetoprotein 399-405, and CEcharacterization of QDs (of differing emission
wavelengths) exclusively conjugated to biotin and
streptavidin 406 . The performance of CE-LIF in
characterizing immunoconjugates of quantum dot-labeled
IgGs suggested that both QDs and CE-LIF can be applied
as a sensitive technique for the detection of biological
molecules 407. However, these reports on the use of QDs
in CE-based immunoassays are not satisfactory, due in
part to a QD-biomolecule conjugates (and
immunoconjuagtes) complex charge:size ratio. In view
of above, further research is required in its development
as a fast and efficient method for performing
immunoassays. Commercially available QD were
characterized using CE using detection system UV
absorption and LIF 408. The applications stemming from
the merging of nanotechnology with microfludics in
electrophoresis haves been reported 409.
CE based on the principles of frontal analysis was

used to characterize the binding of flavonoids to human
serum albumin at near-physiological conditions, thereby,
providing a lot of useful parameters for characterization
of ligandprotein interactions 376. CE-FA was used to
study the interaction of drugs with plasma proteins 377 ,
protein binding of basic drugs 378, protein binding constant,
binding sites of the Strychnos alkaloid-strychnine and
bovine serum albumin 379,380,. CE has the potential to
become a useful technology to characterize liposomal
systems including liposomal drug formulations and
PEGylated liposomal drug formulation 381-383. CE provided
better clues about levels of molecular species, enzymatic
processes, and protein expression occurring in a cell at
different time points in the cell life cycle 384. MEKC CE
method was developed for the quantitative analysis of
cereulide, the emetic toxin produced by Bacillus
cereus 385.
The model binding of the glycopeptide antibiotic
teicoplanin from Actinoplanes teichomyceticus,
immobilized on magnetic microspheres to d-Ala-d-Ala
terminus peptides was reported using microchip capillary
electrophoresis with continuous frontal analysis. The
binding constants obtained using the technique was
comparable with values reported in the literature 386.
Researchers have reported the methodology of CE-LIF
immunoassay for the detection of DNA adducts 387.
The results for the analysis of inorganic ions in whole
blood, specifically lithium demonstrated the versatility of
the CE system for on-site measurement of inorganic ions
388
. Automated, high-resolution, quantitative, highthroughput analysis of mono- and oligosaccharides,
produced by enzymatic digestion of cellohexaose (model
substrate) and lignocellulosic biomass, has been
demonstrated using CE in conjunction with a single-step
fluorophore labeling strategy for sensitive laser-induced
Conclusions and perspectives

CE is a well-known automated analytical technique
that separates cationic, anionic and neutral species
covering both large and small molecules by applying
19
voltage across buffer filled capillaries. This technique

allows for minimal organic consumption, fast analysis time,
high degree of resolution and low operating costs. It is
one of the suitable methods for the characterization and
quantication of molecular interactions of bioactive
molecules. CE is employed in quality control of
pharmaceuticals, biopharmaceuticals, and CE analysis
includes purity determination, assays; analysis of metal
ions, simple organic acids, inorganic anions, carbohydrates
and their derivatives, proteins, DNA and trace level
determinations. CE has been increasingly employed for
the separation of pharmaceutical agents and drugs;
pharmaceutical analysis, assay of active pharmaceutical
ingredients, chiral drug separation, detection of impurities
in drugs, analysis of metal and non-metal ions,
carbohydrates and their derivatives, proteins, DNA, and
assessment of potency and stability of drugs. The use of
CE is almost routine in many hospitals and clinics,
particularly for analyzing serum proteins and disease
markers. Moreover, CE technique is widely accepted by
regulatory authorities.
2.
Camille P. Capillary electrophoresis: Theory and practice;

CRC Press: Boca Raton, 1993.
3.
Landers JP. Handbook of capillary electrophoresis; CRC

Press: Boca Raton, 1994.
4.
Jorgenson JW, Lukacs KD. Zone electrophoresis in opentubular glass capillaries. Anal Chem 1981;53:1298-1302.
6.
Capillary Electrophoresis Methods and Protocols, Series:

Methods in Molecular Biology, Vol. 384, Schmitt-Kopplin,
Philippe (Ed.) 2008, XVIII.
7.
Bartle K, Myers P (Eds.), Capillary Electrochromatography,

RSC, Cambridge, 2001.
8.
Hjertn S. Free zone electrophoresis. Chromatogr Rev

1967;9:122-219.
9.
Jorgenson JW, Lukacs KD. Free-zone electrophoresis in

glass capillaries. Clin Chem 1981;27:1551-1553.
11. Hjertens S, Zhu MD. Adaptation of the equipment for highperformance electrophoresis to isoelectric focusing. J
Chromatogr 1985;346:265-270.
12. Terabe S, Otsuka K, Ichikawa K, Tsuchiya A, Ando T.
Electrokinetic separations in micellar solutions and opentubular capillaries. Anal Chem 1984;56:111-113.
13. Terabe S., Otsuka
K, Ando, T. Electrokinetic
chromatography with micellar solution and open-tubular
capillary. Anal Chem 1985;57:834-841.
14. Cohen AS, Paulus A, Karger BL, High-performance
capillary electrophoresis using open tubes and gels.
Chromatographia 1987;24:15-24.
15. Cohen AS, Karger BL. High-performance sodium dodecylsulfate polyacrylamide-gel Capillary electrophoresis of
peptides and proteins. J Chromatogr 1987;397:409-417.
16. Chankvetadze B. Capillary electrophoresis in chiral
analysis. John Wiley and Sons, Chapter1, p 7, 1997.
17. Tsuda T. Electrochromatography using high applied
voltage. Anal Chem 1987; 59: 521-523.
18. Knox JH, Grant IH. Miniaturisation in pressure and
electroendosmotically driven liquid chromatography: Some
theoretical considerations. Chromatographia 1987;24:135143.
REFERENCES
Kuhn R, Hoffstetter-Kuhn S. Capillary electrophoresis:
Principles and practice; Springer-Verlag: Berlin, 1993.
Baker DR. Capillary electrophoresis. Wiley: New York, 1995.
10. Hjertn S. High-performance electrophoresis: The

electrophoretic counterpart of high-performance liquid
chromatography. J Chromatogr 1983;270:1-6.
Microchip system providing specific advantages is a

potentially valuable tool for pharmaceutical analysis when
compared to traditional separation methods. MEEKC
technique is capable of separating almost every kind of
drug, including cationic, neutral, and anionic drugs. The
use of CE for the determination of drugs in biological
matrices and for therapeutic drug monitoring should be
further explored. Advances in flow injection-capillary
electrophoresis technology have led to enhanced
separation capabilities in the area of pharmaceutical
analysis. In this direction, the fabrication of interfaces
between the flow injection-capillary electrophoresis
components and the microfluidic platform is currently a
focus of researchers.
1.
5.
19. Cohen AS, Najarian DR, Paulus A, Guttman A, Smith JA,

Karger BL. Rapid separation and purification of
oligonucleotides by high-performance capillary gel
electrophoresis. Proc Natn Acad Sci U.S.A. 1988;85: 96609663.
20. Kasper TJ, Melera M, Gozel P, Brownlee RG. Separation
and detection of DNA by capillary electrophoresis. J
Chromatogr 1988;458:303312.
20
21. https://www.beckmancoulter.com/wsrportal/wsr/
industrial/products/capillary-electrophoresis/history-ofce/index.htm
Sixth International Symposium on Human Identification,

Promega Corporation, 1995, pp. 81-87.
36. Moretti TR, Baumstark AL, Defenbaugh DA, Keys KM,
Brown AL, Budowle B. Validation of STR typing by capillary
electrophoresis. J Forensic Sci 2001;46(3):661-676.
22. Guttman A, Cohen AS, Heiger DN, Karger BL. Analytical

and micropreparative ultrahigh resolution of
oligonucleotides by polyacrylamide gel high performance
capillary electrophoresis. Anal Chem 1990;62:137-141.
37. Ho HT, Chang PL, Hung CC, Chang HT. Capillary

electrophoretic restriction fragment length polymorphism
patterns for the mycobacterial hsp65 gene. J Clin Microbiol
2004;42(8):3525-3531.
23. Strege M, Lagu A. Separation of DNA restriction fragments

by capillary electrophoresis using coated fused silica
capillaries. Anal Chem 1991; 63(13):1233-1236.
38. Ohnesorge J, Neusb C, Wtzig H. Quantitation in capillary

electrophoresis-mass spectrometry. Electrophoresis
2005;26:39733987.
24. Kleemib MH, Gilges M, Schomburg G. Capillary

electrophoresis of DNA restriction fragments with
solutions of entangled polymers. Electrophoresis
1993;14:515522.
39. Pereira M, Lai EPC. Capillary electrophoresis for the

characterization of quantum dots after non-selective or
selective bioconjugation with antibodies for immunoassay.
J Nanobiotechnol 2008;6:10 doi:10.1186/1477-3155-6-10
25. Zagurski RJ, McCormick RM. DNA sequencing separations

in capillary gel on a modified commercial DNA sequencing
instrument. Biotechniques 1990;9:74-79.
40. Liu X, Dahdouh F, Salgado M, Gomez FA. Recent advances

in affinity capillary electrophoresis . J Pharm Sci 2009;98:394410.
26. Huang XC, Quesada MA, Mathies RA. DNA sequencing

using capillary array electrophoresis. Anal Chem
1992;64(18):2149-54.
27. Graham CA, Hill AJM. DNA sequencing protocols
:Methods in Molecular Biology Volume 167. Humana Press,
2001.
41. http://www.mass-spec-capital.com/product/cesi-8000optims-technology-beckman-coulter-inc-nyse-200121093.html; http://www.separationsnow.com/coi/cda/

detail.cda?id=26378&type=News&chId=2&page=1
28. Dovichi NJ, Zhang J. DNA sequencing by capillary array

electrophoresis. Methods Mol Biol. 2001;162:85-94.
42. CASSS Award 2011. casss.org/displaycommon.

cfm?an=1&subarticlenbr=562
29. Knox JH, Grant IH. Electrochromatography in packed tubes

using 1.5 to 50 m silica-gels and ODS bonded silica-gels.
Chromatographia 1991;32:317-328.
43. Rogers B, Gibson GTT, Oleschuk RD. Bundled capillary

electrophoresis using microstructured fibres.
Electrophoresis 2011;32:223- 229.
30. Grossman PD, Soane DS. Capillary electrophoresis of

DNA in entangled polymer solutions. J Chromatogr A 1991;
559(1-2): 257-266.
44. Zhang J, Konecny J, Glatz Z, Hoogmartens J, Van

Schepdael A. Application of capillary electrophoresis in
drug metabolism studies. Curr Anal Chem 2007; 3(3):197217.
31. Beckers JL, Everaerts FM, Ackerman

MT.
Isotachophoresis with electroosmotic flow: open versus
closed systems. J Chromatogr A 1991;537:429-442.
45. Ahuja S, Jimidar M (eds.). Capillary electrophoresis

methods for pharmaceutical analysis. Academic Press,
Volume 9 (Separation Science and Technology) 2008.
32. Huang XC, Quesada MA, Mathies RA. DNA sequencing

using capillary array electrophoresis. Anal Chem
1992;64(18):2149-54.
46. Weinberger R. Practical capillary electrophoresis, 2nd

Edition, Academic Press, 2001.
47. Kuhr WG, Monnig CA. Fundamental reviews: Capillary
electrophoresis, Anal Chem 1992;64:389-407.
33. Smith NW, Evans MB. The analysis of pharmaceutical

compounds using electrochromatography. Chromatographia
1994;38:649-657.
34. Karger BL, Chu YH, Foret F. Capillary electrophoresis of
proteins and nucleic acids. Ann Rev Biophys Biomol Struct
1995;24:579-610.
48. Kaiser T, Wittke S, Just I, Krebs R, Bartel S, Fliser D, et al..

Capillary electrophoresis coupled to mass spectrometer
for automated and robust polypeptide determination in
body fluids for clinical use. Electrophoresis 2004; 25(13):
2044-2055.
35. McCord BR, Isenberg AR, Butler JM, Allen RO. Rapid and
automated genetic typing using capillary electrophoresis
for the analysis of STRs and D1S80. Proceedings of the
49. Gijbels K, De Coster J, Bossuyt X. Interference by gelatinbased plasma substitutes in capillary zone electrophoresis.
Clin Chem 2004;50:1473-1475.
21
50. Jouyban A , Kenndler E. Theoretical and empirical

approaches to express the mobility of small ions in capillary
electrophoresis. Electrophoresis 2006;27:992-1005.
62. Henrik L. Separation of pharmaceuticals by capillary

electrophoresis using partial filling and multiple-injections.
Doctoral Dissertation, Disciplinary Domain of Medicine
and Pharmacy, Faculty of Pharmacy, Department of
Medicinal Chemistry, Uppsala universitet, Sweden, Last
updated: 2011-01-28
51. Amini A. Recent developments in chiral capillary

electrophoresis and applications of this technique to
pharmaceutical and biomedicalanalysis. Electrophoresis.
2001; 22(15) :3107-3130.
63. Aguiar FA, de Gaitani CM, Borges KB. Capillary

electrophoresis method for the determination of isradipine
enantiomers: Stability studies and pharmaceutical
formulation analysis. Electrophoresis 2011;32:26732682.
52. Li B, Haynie DT. Chiral drug separation. In: Encyclopedia

of chemical processing, 2006, Taylor & Francis, pp 449458.
64. Hansen SH, Sheribah ZA. Comparison of CZE, MEKC,

MEEKC and non-aqueous capillary electrophoresis for the
determination of impurities in bromazepam. J Pharm Biomed
Anal 2005;39(1-2):322-327.
53. Chang WW, Hobson C, Bomberger DC, Schneider LV.

Rapid separation of protein isoforms by capillary zone
electrophoresis with new dynamic coatings.
Electrophoresis. 2005;26(11):2179-2186.
65. Teng H, Yuan BQ, You TY. Recent advances in application

of nonaqueous aapillary electrophoresis. Chin J Anal Chem
2010;38(11):1670-1677.
54. Parente F, Ah Mew N, Jaeken J, Gilfix BM. A new capillary

zone electrophoresis method for the screening of congenital
disorders of glycosylation (CDG). Clin Chim Acta.
2010;411(1-2):64-66.
66. Cohen AS, Smisek DL, Keohavong P. Capillary gel

electrophoresis of biopolymers. Trends Anal Chem
1993;12(5):195-202.
55. Elbashir AA, Saad B, Abdussalam SMA; Muhd IS, AboulEnein HY. Optimization, validation and application of a
capillary zone electrophoresis method for the assay of
sparfloxacin in pharmaceutical formulation. Anal Lett
2008;41 (14): 2608-2620 .
67. Zhu Z, Lu JL, Liu S. Protein separation by capillary gel

eectrophoresis: A review. Anal Chim Acta 2012;709:21-31.
56. Riekkola ML. Recent advances in nonaqueous capillary

electrophoresis. Electrophoresis 2002; 23: 38653883.
68. Guttman A. On the separation mechanism of capillary

sodium dodecyl sulfate-gel electrophoresis of proteins.
Electrophoresis 1995;16:611-616.
57. Altria KD, Wallberg M, Westerlund D. Separation of a range

of cations by non-aqueous capillary electrophoresis using
indirect and direct detection. J Chromatogr B 1998;714:99104.
69. Tsai SW, Loughran M, Susuki H, Karube, I. Native and

sodium dodecylsulfate-capillary gel electrophoresis of
proteins on a single microchip. Electrophoresis
2004;25(3):494-501.
58. Wang F, Khaledi MG. Chiral separations by nonaqueous

capillary electrophoresis. Anal Chem 1996;68 (19): 34603467.
70. Salas-Solano O, Tomlinson B, Du S, Parker M, Strahan A,

Ma S. Optimization and validation of a quantitative capillary
electrophoresis sodium dodecyl sulfate method for quality
control and stability monitoring of monoclonal antibodies.
Anal Chem 2006;78(18):6583-6594.
59. Carlsson Y, Hedeland M, Bondesson U, Pettersson C.

Non-aqueous capillary electrophoretic separation of
enantiomeric amines with (-)- 2,3:4,6-di-O-isopropyliden2-keto-L-gulonic acid as chiral counter ion. J. Chromatogr
2001; 922:303-311.
71. Miksk I, Sedlkov P, Mikulkov K, Eckhardt A, Cserhati

T, Horvth T. Matrices for capillary gel electrophoresis
a brief overview of uncommon gels. Biomed Chromatogr
2006;20:458465.
60. Hedeland Y, Hedeland M, Bondesson U, Pettersson C.

Chiral separation of amines with N-benzoxycarbonylglycylL-proline as selector in non-aqueous capillary
electrophoresis using methanol and 1,2-dichloroethane in
the background electrolyte. J Chromatogr A 2003; 984:261271.
72. Lee A, Whitesides GM. Analysis of inorganic

polyphosphates by capillary gel electrophoresis. Anal
Chem 2010;82:68386846.
73. Lin QH, Cheng YQ, Dong YN, Zhu Y, Pan JZ, Fang Q.
High-speed separation of proteins by sodium dodecyl
sulfate-capillary gel electrophoresis with partial translational
spontaneous sample injection. Electrophoresis
2011;32: 28982903.
61. Lodn H, Hedeland Y, Hedeland M, Bondesson U,

Pettersson C. Development of a chiral non-aqueous
capillary electrophoretic system using the partial filling
technique with UV and mass spectrometric detection. J
Chromatogr. A 2003;986:143-152.
74. Lausch R, Scheper T, Reif OW, Schlsser J, Fleischer J,

Freitag R. Rapid capillary gel electrophoresis of proteins. J
22
Chromatogr A 1993; 654(1):190-195.
Michotte Y (eds.), Taylor and Francis, Florida, 2010, pp.

459-500.
75. Mellado MCM, Franco C, Coelho A, Alves PM, Simplcio

AL. Sodium dodecyl sulfate-capillary gel electrophoresis
analysis of rotavirus-like particles. J Chromatogr A
2008;1192(1):166-72.
87. Mangelings D, Vander Heyden Y. Chiral separations by

capillary electrophoresis. Chapter in Chiral separation
methods for pharmaceutical and biotechnology products.
S. Ahuja S (ed.), John Wiley and Sons, New Jersey, 2010,
pp. 331 - 382.
76. Yao S, Anex DS, Caldwell WB, Arnold DW, Smith KB,
Schultz PG. SDS capillary gel electrophoresis of proteins in
microfabricated channels. Proc Natl Acad Sci USA 1999; 9:
53725377.
88. Remcho VT, Vallano PT, Lord GA, Gordon DB, Dermaux A,
Sandra P, et al. Capillary Electrochromatography: Bartle
KD, Myers P, (eds.) RSC Publishing, 2001.
77. Lu JJ, Zhu Z, Wang W, Liu S. Coupling sodium dodecyl

sulfatecapillary polyacrylamide gel electrophoresis with
Matrix-assisted laser desorption ionization time-of-flight
mass spectrometry via a poly(tetrafluoroethylene)
membrane. Anal Chem 2011;83(5):1784-1790.
89. Euerby MR, Gillott NC. Pharmaceutical applications of

capillary electrochromatography, Chapter 7, pp 107-124.
In: Bartle KD, Myers P. Capillary electrochromatography:
RSC chromatography monographs. Royal Society of
Chemistry, 2001
78. Hunt G, Nashabeh W. Capillary electrophoresis sodium

dodecyl sulfate nongel sieving analysis of a therapeutic
recombinant monoclonal antibody:
A
biotechnology perspective. Anal Chem 1999;71: 2390-2397.
90. Kumar AP, Park JH. Fast separations of chiral -blockers

on a cellulose tris(3,5-dimethylphenylcarbamate)-coated
zirconia
monolithic
column
by
capillary
electrochromatography. J Chromatogr A 2011;1218(31):536973.
79. Zhang J, Burman S, Guntur S, Foley JP. Method

development and validation of capillary sodium dodecyl
sulfate gel electrophoresis for the characterization of a
Monoclonal antibody. J Pharm Biomed Anal 2010;53:12361243.
91. Ping G, Schmitt-Kopplin P, Zhang Y, Baba Y. Capillary

electrochromatography and on-line concentration.
Methods Mol Biol. 2008;384:751-69.
80. Caroline JC, Marianne B, Dorte M, Peter H, Charlotte

Guldborg N. Capillary gel electrophoresis : a simple method
for identification of mutations and polymorphisms in the
CEBPA gene in patients with acute myeloid leukaemia. Eur
J Haematol 2008;81(4):273-280.
92. Barbato F, Grumetto L, Carpentiero C, Rocco A, Fanali S.

Capillary electrochromatography as a new tool to assess
drug affinity for membrane phospholipids. J Pharm Biomed
Anal 2011;54(5):893-899.
93. Mangelings D, Vander Heyden Y. Enantioselective capillary
electrochromatography: Recent developments and new
trends. Electrophoresis 2011;32: 25832601.
81. Remcho VT. Capillary electrokinetic chromatography (CEC):

An introduction to a high-efficiency microanalytical
technique. Chem Educat 1997;2(2):
94. Terabe S, Otsuka K, Ichikawa K, Tsuchiya A, Ando T.

Electrokinetic separation with micellar solution and opentubular capillaries. Anal Chem 1984;56: 111-113.
82. Erim FB. From capillary electrophoresis to capillary

electrochromatography:An overview. Hacettepe J Biol &
Chem 2009;37(2):77-82.
83. Mangelings D, Perrin C, Massart DL, Maftouh M, Eeltink
S, Kok WT, et al. Optimisation of the chlorthalidone chiral
separation by capillary electrochromatography. Anal Chim
Acta 2004;509 ;11-19.
95. Akbay SA, Rizvi A, Shamsi SA. Simultaneous

enantioseparatoin and tandem UV-MS detection of eight
beta-blockers in micellar electrokinetic chromatography
using a chiral molecular micelle. Anal Chem 2005;77:16721683.
84. Adu JK, Euerby MR, Tettey JNA, Skellern GG. Capillary
electrochromatography of pharmaceuticals, Chapter 17,
pp 439-476. In: Capillary electrophoresis methods for
pharmaceutical analysis, Volume 9 of Separation Science
and Technology. Ahuja S, Jimidar MI (eds). Elsevier, 2008.
96. Hu Q, Zhou TS, Zhang H, Li H, Fang YZ. Study on the

separation and determination of three water-soluble
vitamins in pharmaceutical preparations and food by
micellar electrokinetic chromatography with amperometric
electrochemical detection, Anal Chim Acta 2001;437: 123.
85. Kasicka V. Recent developments in CE and CEC of peptides.

Electrophoresis 2008;29( 1):179-206.
97. Rizvia SAA, Dob DP, Salehc AM. Fundamentals of micellar

electrokinetic chromatography (MEKC). Eur J Chem
2011;2(2):276 281.
86. Mangelings D, Vander Heyden Y. Recent applications in

capillary electrochromatography. Chapter in Chiral
separations by capillary electrophoresis. Van Eeckhaut A,
98. Sirn H, Seppnen-Laakso T, Oresic M. Capillary

electrophoresis with UV detection and mass spectrometry
23
in method development for profiling metabolites of steroid

hormone metabolism. J Chromatogr B Analyt Technol
Biomed Life Sci. 2008;;871(2):375-382.
advances in the methodology, optimisation and application

of MEEKC. Electrophoresis 2009;30(1):65-82.
113. Ryan R, Donegan S, Power J, Altria K. Advances in the
theory and application of MEEKC. Electrophoresis
2010;31(5):755-767.
99. Molina M, Silva M. Micellar electrokinetic

chromatography: current developments and future.
Electrophoresis 2002;23(22-23):3907-3921.
114. Ryan R, McEvoy E, Donegan S, Power J, Altria K. Recent

developments in the methodology and application of
MEEKC. Electrophoresis. 2011;32(1):184-201.
100. Terabe S Capillary separation: micellar electrokinetic

chromatography. Ann Rev Anal Chem 2009; 2: 99-120.
101. Pyell, U. Electrokinetic chromatography: theory,
instrumentation and application. John Wiley & Sons, Ltd:
2006.
115. Altria KD, Broderick M, Donegan S, Power J. The use of

novel waterin-oil microemulsions in microemulsion
electrokinetic chromatography. Electrophoresis 2004; 25:
645-652.
102. Quirino JP, Terabe S. Electrokinetic chromatography. J

Chromatogr A 1999;856:465-482.
116. Mrestani Y. Afnity of drugs to pharmaceutical vehicle

systems: Microemulsions. In: Affinity capilliary
electrophoresis in pharmaceutics and biopharmaceutics,
Neubert RHH, Rutinger HH (eds.), Marcel Dekker, Inc. New
York, 2003.
103. Xia Z, Jiang X, Mu X, Chen H. Improvement of

microemulsion electrokinetic chromatography for
measuring octanol-water partition coefficients.
117. Gao L, Liu S. Cross-linked polyacrylamide coating for

capillary isoelectric focusing. Anal Chem 2004;76 (24): 7179
-7186.
104. Terabe S, Matsubara N, Ishihama Y, Okada Y.

Microemulsion
electrokinetic
chromatography:
Comparison with miceller electrokinetic chromatography.
J Chromatogr 1992;608:23-29.
118. Yang C, Wang S, Chang C, Wang Y, Hu X. Capillary

Isoelectric focusing with an open tubular immobilized pH
gradien. Anal Chem 2010;82 (5):1580-1583.
105. Terabe S, Otsuka K, Ando T. Electrokinetic chromatography

with miceller solution and open tubular capilliary. Anal
Chem 1985;57:834-841;
119. Kuroda Y, Yukinaga H, Kitano M, Noguchi T, Nemati M,

Shibukawa A, et al. On-line capillary isoelectric focusingmass spectrometry for quantitative analysis of peptides
and proteins. J Pharm Biomed Anal 2005;37(3):423-438.
106. Marsh A, Clark B, Broderick M, Power J, Donegan S, Altria

K. Recent advances in microemulsion electrokinetic
chromatography. Electrophoresis 2004;25:3970-3908.
120. Yang C, Zhang W, Zhang J, Duan J, Zhang Y. Protocol of

capillary isoelectric focusing to separate extremely acidic
and basic proteins. J Sep Sci 2005;28:78-86.
107. Kojtari AB, Guetschow ED, Foley JP. The effect of

cosurfactant-modified micelles on chiral separations in
EKC. Electrophoresis 2009;30:2829-2836.
108. Kojtari A, Foley JP. Effect of microemulsion component
purity on the chromatographic figures of merit in chiral
microemulsion electrokinetic chromatography. J
Chromatogr A 2009;1216:3488-3491.
121. Dickerson JA, Ramsay LM, Dada OO, Cermak N, Dovichi

NJ. Two-dimensional capillary electrophoresis: capillary
isoelectric focusing and capillary zone electrophoresis with
laser-induced fluorescence detection. Electrophoresis
2010;31(15):2650-2654.
109. Kahle KA, Foley JP. Chiral microemulsion electrokinetic

chromatography: Effect of cosurfactant identity on
enantioselectivity, methylene selectivity, resolution, and
other chromatographic figures of merit. Electrophoresis.
2006;27(21):4321-33.
122. Dada OO, Ramsay LM, Dickerson JA , Cermak N, Jiang R,

Zhu C, Dovichi NJ. Capillary array isoelectric focusing with
laser-induced fluorescence detection: milli-pH unit
resolution and yoctomole mass detection limits in a 32channel system. Anal Bioanal Chem 2010; 397(8):3305-3310.
110. Huie CW. Recent applications of microemulsion

electrokinetic chromatography. Electrophoresis
2006;27(1):60-75.
123. Fonslow BR, Kang SA, Gestaut DR, Graczyk B, Davis TN,
Sabatini DM, John R. YatesIII JR. Native capillary isoelectric
focusing for the separation of protein complex isoforms
and subcomplexes. Anal Chem 2010;82:66436651.
111. McEvoy E, Marsh A, Altria K, Donegan S, Power J. Recent

advances in the development and application of
microemulsion EKC. Electrophoresis 2007;28(1-2):193-207.
124. Li SFY. Capillary electrophoresis: Principles, practice, and

applications. Elsevier Science Publishers: The Netherlands,
1992.
112. Ryan R, Donegan S, Power J, McEvoy E, Altria K. Recent

24
125. Zhang B, Matsunaga A, Saku K. Associations among

plasma lipoprotein subfractions as characterized by
analytical capillary isotachophoresis, apolipoprotein E
phenotype, Alzheimer disease, and mild cognitive
impairment. Arteriosclerosis, Thrombosis, and Vascular
Biol 2004;24:e144.
137. Ruttinger HH. Theory of afnity electrophoresis. In:

Affinity capillary electrophoresis in pharmaceutics and
biopharmaceutics . Neubert RHH, Ruttinger HH (eds.),
Marcel Dekker Inc. New York, 2003.
138. Ishihama Y. Determination of physicochemical parameters.
In:Affinity capillary electrophoresis in pharmaceutics and
126. Kuback P, Mikus P, Valskov I, Havrnek E.

Determination of promethazine hydrochloride in
pharmaceuticals by capillary isotachophoresis. Methods
Find Exp Clin Pharmacol 2005;27(8):529-32.
139. Azad M, Hernandez L, Plazas A Rudolph M, Gomez FA.

Determination of binding constants between the antibiotic
ristocetin A and D-Ala-D-Ala terminus peptides by affinity
capillary electrophoresis. Chromatographia 2003; 57: 339344.
127. Wang Y, Wang H, Ju S, Pu J, Wang Z, MM. Analysis of

dyslipidemia in nephrotic syndrome by capillary
isotachophoresis. LabMedicine 2009;40:544-547.
128. Kurzawa M, Jastrzbska A, A, Sz!yk E. Application of
isotachophoretic and conductometric methods for
neomycin trisulphate determination. Chemical Papers 2009;
63(3):255-260.
140. Azad MA, Kaddis J, Villareal V, Hernandez L, Silverio C,

Gomez FA. Affinity capillary electrophoresis to examine
receptor-ligand interactions. In: Capillary electrophoresis
of proteins and peptides; Strege MA, Lagu AL, Eds.;
Humana Press: Totowa, 2004, pp 153-168.
129. Kuback P, Mikus P, Valskov I, Havrnek E.Chiral

separation of alkylamine antihistamines in pharmaceuticals
by capillary isotachophoresis with charged cyclodextrin.
Drug Dev Ind Pharm. 2007;33(11):1199-204.
141. Linscheid MW. Afnity capillary electrophoresis: DNA

interactions with peptides, proteins, and modied DNA.
In: Affinity capilliary electrophoresis in harmaceutics and
biopharmaceutics, Neubert RHH, Rutinger HH (eds.),
Marcel Dekker, Inc. New York, 2003.
130. Urbnek M, Posp"#ilov M, Pol#ek M. Determination

of bopindolol in pharmaceuticals by capillary
isotachophoresis. J Pharm Biomed Anal 2002; 28(3-4):509515.
142. Kiessig S, Thunecke F. Afnity of drugs to proteins and

proteinprotein interactions. In: Affinity capilliary
Neubert RHH, Rutinger HH (eds.), Marcel Dekker, Inc. New
York, 2003.
131. Wu Y, Wang Y, Zhao Z, Wu K, Wang Y, Yan C. Pressurized

capillary electrochromatography: Instrumentation,
columns, and applications. Amer Lab 2010; 42(2):38-41.
143. El-Hady D, Khne S, El-Maali N, Wtzig H. Precision in

affinity capillary electrophoresis for drug-protein binding
studies. J Pharm Biomed Anal. 2010;52(2):232-241.
132. Krull I S, Stevenson R L, Misty K, Swartz M E, Capillary

electrochromatography and pressurized flow capillary
electrochromatography, HNB Publishing, New York, 2000,
240 pp.
144. Schwarz MA, Hauser PC. Afnity of drugs to

pharmaceutical vehicle systems: micelles. In: Affinity
capilliary electrophoresis in pharmaceutics and
biopharmaceutics, Neubert RHH, Rutinger HH (eds.),
Informa Healthcare 2003, 2003.
133. Lin ZA, Wu XP, Lin XC, Xie ZH. End-column

chemiluminescence detection for pressurized capillary
electrochromatographic analysis of norepinephrine and
epinephrine. J Chromatogr A 2007;1170:118121.
145. Jose Z, Dinora C, Alejandra; R, Violet C, Gomez, Frank A.

Multiple-injection affinity capillary electrophoresis. LC-GC
North America; 2006; 24(10):11-18.
134. Qu QS, Mangelings D, Shen F, Hua XY, Yan C, Zhang YK,

et al. Pressurized capillary electrochromatographic assay
of trimethoprim impurities using 1 microm particle-based
columns. J Chromatogr A 2007;1169: 228234.
146. Hongxu C, Xinxiang Z. Development of immunoaffinity

capillary electrophoresis. Chinese Journal of
Chromatography 2009;27(5):631-641.
135. Wu Y, Zhang X, Wei J, Xue Y, Bahatibieke M, Wang Y, et al.

Recent advances and applications of capillary
electrochromatography and pressurized capillary
electrochromatography. Se Pu 2009;27(5):609-620.
147. Guzman NA, Blanc T, Terry M. Phillips TM. Immunoaffinity

capillary electrophoresis as a powerful strategy for the
quantification of low-abundance biomarkers, drugs, and
metabolites in biological matrices. Electrophoresis 2008;
29(16): 32593278.
136. Schiewe J. Principles of capilliary electrophoresis. In:

Affinity capillary electrophoresis in pharmaceutics and
148. Kalish H, Phillips TM. Application of immunoaffinity

capillary electrophoresis to the measurements of secreted
25
cytokines by cultured astrocytes. J Sep Sci 2009 ;32 (10) :

1605-1612.
2007;10:16-18.
162. Colyer CL, Mangru SD, Harrison DJ. Microchip-based
capillary electrophoresis of human serum proteins. J
Chromatogr A 1997;781(1-2):271-276.
149. Guzman NA, Phillips TM. Immunoaffinity capillary

electrophoresis: A new versatile tool for determining protein
biomarkers in inflammatory processes. Electrophoresis
2011; 32:15651578.
163. Chiem N, Harrison DJ. Microchip-based capillary

electrophoresis for immunoassays: Analysis of monoclonal
antibodies and theophylline. Anal Chem 1997;69 (3): 373378.
150. Khandurina J, Guttman A. Microscale separation and

analysis. Curr Opin Chem Biol 2003;7:595-602.
151. Rozing G. Trends in HPLC column formatsmicrobore,
nanobore and smaller. LC GC Europe 2003;16:14-19.
164. Zhuang GS, Liu J, Jia CP, Jin QH, Zhao JL, Wang HM.
Microchip-based capillary electrophoresis for
determination of lactate dehydrogenase isoenzymes. J Sep
Sci 2007;30:13501356.
152. Legido-Quigley C, Marlin ND, Melin V, Manz A, Smith NW.

Advances in capillary electrochromatography and microhigh performance liquid chromatography monolithic
columns for separation science. Electrophoresis 2003; 24:
917-944.
165. Li SFY, Larry J. Kricka LJ. Clinical analysis by microchip

capillary electrophoresis. Clin Chem 2006;52(1):3745.
166. Currie CA. Capillary and microchip electrophoresis systems
for pharmaceutical applications. Ph D Thesis, University
of Cincinnati, 2009; http://gateway.proquest.com/
o p e n u r l % 3 f u r l _ v e r = Z 3 9 . 8 8 2004%26res_dat=xri:pqdiss%26rft_val_fmt=info:ofi/
fmt:kev:mtx:dissertation%26rft_dat=xri:pqdiss:3368451.
153. Deyl Z, Svec F (Eds.). Capillary electrochromatography,

Amsterdam: Elsevier 2001.
154. Aboul-Enein HY, Ali I. Nano chromatography and capillary
electrophoresis: Pharmaceutical and environmental
analyses, Wiley VCH, 2011.
167. Development of microchip-based capillary electrophoresis

system and study of its application. http://
www.rescancer.com/breast-cancer/183.html
155. Ali I, Aboul-Enein HY, Gupta VK. Microchip-based nano

chromatography and nano capillary electrophoresis in
genomics and proteomics. Chromatographia 2009; 69(
Supplement 1)13-22.
168. Guijt RM, Baltussen E, van der Steen G, Schasfoort RBM,

Schlautmann S, Billiet H AH, et al. New approaches for
fabrication of microfluidic capillary electrophoresis devices
with on-chip conductivity detection. Electrophoresis,
2001;22: 23524.
156. Ali I, Abdoul-Enein H Y, Gupta VK. Nanochromatography

and nanocapillary electrophoresis - Pharmaceutical and
environmental analyses. 2008, John Wiley & Sons, Inc.,
Hoboken, NJ, USA. Chapter 8.
169. Wang C, Oleschuk R, Ouchen F, Li J, Thibault, P., Harrison,

D. J. Integration of immobilized trypsin bead beds for protein
digestion within a microfluidic chip incorporating capillary
electrophoresis separations and an electrospray mass
spectrometry interface. Rapid Commun Mass SP
2000;14: 13771383.
157. Wu RG, Yang CS, CC, Tseng FG. Nanocapillary

electrophoretic electrochemical chip: towards analysis of
biochemicals released by single cells. Interface Focus
2011;1: 744753.
158. Hsieh YL, Ho TY. Automated physical design of microchipbased capillary electrophoresis systems. Proceeding VLSID
11 Proceedings of the 2011 24th International Conference
on VLSI Design IEEE Computer Society Washington, DC,
USA 2-7 Jan. 2011, pp 165 - 170.
170. Tutorials: Assay: Microfluidic capillary electrophoresis:

Real-time kinetic assays for kinases, phosphatases, and
proteases. Genet Eng Biotech News 2006;26(8).
171. Fu LM, Leong JC, Lin CF, Tai CH, Tsai CH. High performance
microfluidic capillary electrophoresis devices. Biomed
Microdevices 2007;(3):405-412.
159. Xie W, Yang R, Xu J, Zhang L, Xing W, Cheng J. Microchipbased capillary electrophoresis systems. Capillary
electrophoresis of nucleic acids. Methods Mol Biol
2001;162(Part I): 67-83.
172. He QH, Fang Q, Du WB, Fang ZH. Fabrication of a

monolithic sampling probe system for automated and
continuous sample introduction in microchip-based CE,
Electrophoresis 2007; 28(16): 2912-2919.
160. Breadmore MC. Capillary and microchip electrophoresis:

Challenging the common conceptions. J Chromatogr A
Available online 28 September 2011.
173. Zeng HL, Li H, Wang X, Lin JM. Chiral separation of FITClabeled amino acids with gel electrochromatography using
a polydimethylsiloxane microfluidic device. J Capill
Electrophor Microchip Technol. 2007;10(1-2):19-24.
161. Greenspoon SA, Yeung SHI, Ban JD, Mathies RA.

Microchip capillary electrophoresis: Progress toward an
integrated forensic analysis system. Profiles in DNA
26
174. Fan LY, Chen HL, Chen XG, Hu ZD. Separation and
determination of sulfonamides in pharmaceutical
preparations by a microfluidic capillary electrophoresis
system with a continuous sample introduction interface. J
Sep Sci 2003;26:13761382
187. Mikkelsen SR, Cortn E. Capillary electrophoresis in

bioanalytical chemistry, John Wiley & Sons, Inc., Hoboken,
NJ, USA. 2004.
188. Diekmann J, Adams KL, Klunder GL, Evans L, Steele P,
Vogt C, et al. Portable microcoil NMR detection coupled to
capillary electrophoresis . Anal Chem 2011; 83(4);1328-1335.
175. Ali I, Aboul-Enein HY, Gupta VK, Li SF. Pharmaceuticals

analysis by capillary electrophoresis at nanolevel detection.
J Capill Electrophor Microchip Technol. 2006;9(5-6):85-99.
189. Wolters AM, Jayawickrama DA, Webb AG, Sweedler JV.

NMR detection with multiple solenoidal microcoils for
continuous-flow capillary electrophoresis. Anal Chem
2002;74(21):5550-5555.
176. Skoog DA, Holler FJ, Crouch SR. Principles of instrumental

analysis. 6th ed. Chapter 30, Thomson Brooks/Cole
Publishing: Belmont, CA 2007.
190. Hapuarachchi S, Janaway GA, Aspinwall CA. Capillary

electrophoresis with a UV light-emitting diode source for
chemical monitoring of native and derivatized fluorescent
compounds. Electrophoresis. 2006;27(20):4052-4059.
177. Bao J, Krylova SM, Wilson DJ, Reinstein O, Johnson PE,

Krylov SN. Kinetic Capillary electrophoresis with massspectrometry detection (KCE-MS) facilitates label-free
solution-based kinetic analysis of proteinsmall molecule
binding. ChemBioChem 2011;12: 25512554.
191. Altria KD, Elder D. Overview of the status and applications

of capillary electrophoresis to the analysis of small
molecules. J Chromatogr A 2004;1023(1):1-14.
178. Lin H, Natan M, Keating C. Surface-enhanced raman

scattering:
A structure-specific detection method for
capillary electrophoresis. Anal Chem 2000;72:5348-5355.
192. Altria K, Marsh A, Snger-van de Griend C. Capillary

electrophoresis for the analysis of small-molecule
pharmaceuticals. Electrophoresis 2006; 27: 22632282.
179. Alnajjar AO. Capillary electrophoresis with fluorescence

detection for sensitive analysis of morphine and 6acetylmorphine in human urine. Acta Chromatogr 2008;
20( 2): 227-238.
193. Xiong B, Wang W, Miao X, Liu L, Wang L, Zhou X, et al.

Simultaneous laser-induced fluorescence, coaxial thermal
lens spectroscopy and retro-reflected beam interference
detection for capillary electrophoresis. Talanta In Press,
Accepted Manuscript Available online 25 October 2011.
180. Yin XB, Wang E. Capillary electrophoresis coupling with

electrochemiluminescence detection: a review. Anal Chim
Acta 2005; 533(2);113-120.
194. Tu J, Halsall HB, Seliskar CJ, Limbach PA, Arias F,

Wehmeyer KR, et al. Estimation of logP(ow) values for
neutral and basic compounds by microchip microemulsion
electrokinetic chromatography with indirect fluorimetric
detection (muMEEKC-IFD). J Pharm Biomed Anal
2005;38(1):1-7.
181. Xing-Hu JI, Qin-Feng XU, Zhi-Ke HE. Recent advances in

chemiluminescence detection for capillary electrophoresis.
Chin J Anal Chem 2008;36(11):1579-1586.
182. Zemann AJ, Schnell E, Volgger D, Bonn GK. Contactless
conductivity detection for capillary electrophoresis. Anal
Chem 1998;70 (3):563-567.
195. Currie CA, Heineman WR, Halsall HB, Seliskar CJ, Limbach
PA, Arias F, et al. Estimation of pK(a) values using
microchip capillary electrophoresis and indirect
fluorescence detection. J Chromatogr B Analyt Technol
Biomed Life Sci 2005;824(1-2):201-205.
183. Pormsila W, Morand R, Krhenbhl S, Hauser PC. Capillary

electrophoresis with contactless conductivity detection
for the determination of carnitine and acylcarnitines in
clinical samples. J Chromatogr B Analyt Technol Biomed
Life Sci. 2011;879(13-14):921-926.
196. Pumera M, Escarpa A. Nanomaterials as electrochemical

detectors in microfluidics and CE: fundamentals, designs,
and applications. Electrophoresis 2009;30(19):3315-3323.
184. Kappes T, Hauser PC. Simplified amperometric detector

for capillary electrophoresis. Analyst 1999;124:1035-1039.
197. Olivares JA, Nguyen NT, Yonker CR, Smith RD. On-line
mass spectrometric detection for capillary zone
electrophoresis. Anal Chem. 1987;59:1230-1232.
185. Richter EM, Fracassi da Silva JA, Gutz IGR, do Lago CL,
Angnes L. Disposable twin gold electrodes for
amperometric detection in capillary electrophoresis.
Electrophoresis 2004; 25: 29652969.
198. Smith RD, Olivares JA, Nguyen NT, Udseth HR. Capillary
zone electrophoresis-mass spectrometry using an
electrospray ionization interface. Anal Chem 988;60:436441.
186. Tsai DM, Shih PR, Tai HW, Liu CY, Zen JM. A capillary
electrophoresis end-column amperometric detection
system incorporating disposable copper-plated screenprinted carbon electrodes. J Chin Chem Soc 2005;52: 773779.
199. Chamberlain J. How charge based separation are applied

in pharmaceutical analysis? Pharm J 2005;274:458-459.
27
200. Britz-McKibbin P. Capillary electrophoresis-electrospray

ionization-mass spectrometry (CE-ESI-MS)-based
metabolomics. Methods Mol Biol 2011;708:229-246.
to atmospheric pressure photoionization

spectrometry. Electrophoresis 2008;29:11-19.
mass
212. Hommerson P, Khan AM, de Jong GJ, Somsen GW.

Capillary electrophoresis-atmospheric pressure chemical
ionization-mass spectrometry using an orthogonal
interface: Set-up and system parameters. J Am Soc Mass
Spectrom 2009; 20:13111318.
201. Hansen SH, Bendahl L, Gammelgaard B, Jns O, Farver O.

Hyphenation of CE to ICP-MS and to sheathless
electrospray-MS for high sensitivity and selectivity in
bioanalysis. Chromatographia 2002;55(Supplement 1):S15S19.
213. Schappler J, Veuthey JL, Rudaz S. Coupling CE and

microchip-based devices with mass spectrometry In
Capillary Electrophoresis Methods for Pharmaceutical
Analysis. Capillary Electrophoresis Methods for
Pharmaceutical Analysis. pp. 477-521, Elsevier, Academic
Press, Amsterdam , 2008.
202. Prange A, Prfrock D. Application of CEICPMS and CE

ESIMS in metalloproteomics: challenges, developments,
and limitations. Anal Bioanal Chem 2005;383(3):372-389.
203. Methods in Molecular Biology, Vol. 162: Introduction to
the Capillary electrophoresis of nucleic acids, Vol. 1:
Practical applications of capillary electrophoresis Edited
by: K. R. Mitchelson and J. Cheng Humana Press Inc.,
Totowa, NJ.2001.
214. Matusiewicz H, lachciski M. Interfacing a microchipbased capillary electrophoresis system with a microwave
induced plasma spectrometry for copper speciation. Central
Eur J Chem 2011;9(5): 896-903.
204. Methods in Molecular Biology, Vol. 163: Capillary

Electrophoresis of nucleic acids, Vol. 2: Practical
applications of capillary electrophoresis . K. R. Mitchelson
KR, Cheng J (Eds.) Humana Press Inc., Totowa, NJ.2001.
215. Viberg P, Jornten-Karlsson M, Petersson P, Spegel P,

Nilsson S. Nanoparticles as pseudostationary phase in
capillary electrochromatography/ESI-MS. Anal Chem 2002;
74:4595-4601.
205. Huhn C, Ramautar R, Wuhrer M, Somsen GW. Relevance

and use of capillary coatings in capillary electrophoresis
mass spectrometry. Anal Bioanal Chem 2010;396(1): 297314.
216. Malmstrm D, Axen J, Bergquist J, Viberg P, Spegel P.

Continuous full filling capillary electrochromatography
electrospraying chromatographic nanoparticles.
Electrophoresis 2011;32(2):1-7.
206. Mol R, Kragt E, Jimidar I, de Jong GJ, Somsen GW. Micellar

electrokinetic chromatography-electrospray ionization
mass spectrometry for the identification of drug impurities.
J Chromatogr B Analyt Technol Biomed Life Sci. 2006;
843(2):283-288.
217. Axen J, Malmstrm D, Axelsson B-O, Petersson P, Sjberg

PJR. Efforts to improve detection sensitivity for capillary
electrophoresis coupled to atmospheric pressure
photoionization mass spectrometry. Rapid Commun Mass
SP 2010; 24(9) 1260-1264.
207. Zhong X, Maxwell EJ, Ratnayake C, Mack S, Chen DDY.

Flow-through microvial facilitating interface of capillary
isoelectric focusing and electrospray ionization mass
spectrometry. Anal Chem 2011; 83(22):8748-8755.
218. Malmstrm D, Axen J, Bergquist J, Viberg P, Spegel P.

Continuous full filling capillary electrochromatography
electrospraying chromatographic nanoparticles.
Electrophoresis 2011;1(32):261-267.
208. Zhang Z, Wang J, Hui L, Li L. Membrane-assisted capillary

isoelectric focusing coupling with matrix-assisted laser
desorption/ionization-Fourier transform mass spectrometry
for neuropeptide analysis. J Chromatogr A 2011;1218
(31):5336-5343.
219. Klampfl CW. CE with MS detection: A rapidly developing

hyphenated technique. Electrophoresis 2009;30:S83S91.
220. Gaspar A, Englmann M, Fekete A, Harir M, Schmitt-Kopplin
P. Trends in CE- MS 2005-2006. Electrophoresis 2008; 29(1):
66-79.
209. Himmelsbach M, Haunschmidt M, Buchberger W, Klampfl

CW. Microemulsion electrokinetic chromatography with
on-line atmospheric pressure photoionization mass
spectrometric detection. Anal Chem 2007;79:1564-1568.
221. Groessl M, Hartinger CG, Polec-Pawlak K, Jarosz M, Keppler

BK. Capillary electrophoresis hyphenated to inductively
coupled plasma-mass spectrometry: A novel approach for
the analysis of anticancer metallodrugs in human serum
and plasma. Electrophoresis 2008;29: 22242232.
210. Hommerson P, Khan AM, de Jong GJ, Somsen GW.

Comparison of electrospray ionization and atmospheric
pressure photoionization for coupling of micellar
electrokinetic chromatography with ion trap mass
spectrometry. J Chromatogr 2008;1204(2):197-203.
222. Sun H, Li l, Su M. Simultaneous determination of proline

and pipemidic acid in human urine by capillary
electrophoresis with electrochemiluminescence detection.
J Clin Lab Anal 2010;24: 327 333.
211. Schappler J, Guillarme D, Rudaz S, Veuthey JL.

Microemulsion electrokinetic chromatography hyphenated
28
223. Lin Z, Xie Z. Direct determination of amino acids by

pressurized capillary electrochromatography with
chemiluminescence detection. J Sep Sci 2008;31: 28522859.
toxicology. Therapeutic Drug Monitoring 2002; 24(2):222231.

237. Zhang J, Chakraborty U, Foley JP. Determination of residual
cell culture media components by MEKC. Electrophoresis
2009;30:3971-3977.
224. Petriska I, Polsek M. Electromigration analysis methods

in quality control of pharmacopoeial herbal drugs. Ceska a
Slovenska farmacie casopis Ceske farmaceuticke
spolecnosti a Slovenske farmaceuticke spolecnosti
2004;53(2):61-66.
238. Blaschke G. Chapter 8. Interactions between chiral drugs

and cyclodextrins. Affinity capillary electrophoresis in
pharmaceutics and biopharmaceutics. Neubert RHH,
Ruttinger HH (Eds.) Informa Healthcare, 2003.
225. Mohammad AA, Petersen JR, Bissell MG. Steroid analysis

by micellar electrokinetic capillary chromatography. Clinical
applications of capillary electrophoresis. Methods Mol
Med1999; 27: 177-187.
239. Timerbaev AR, Hartinger CG, Keppler BK. Metallodrug

research and analysis using capillary electrophoresis.
Trends Anal Chem 2006;25(9):868-875.
226. Suntornsuk L . Recent advances of capillary electrophoresis

in pharmaceutical analysis. Anal Bioanal Chem 2010,
398(1):29-52.
240. Mohammadi A, Nojavan S, Rouini M, Fakhari AR. Stability

evaluation of tramadol enantiomers using a chiral stabilityindicating capillary electrophoresis method and its
application to pharmaceutical analysis. J Sep Sci
2011;34(13):16131620.
227 Suntornsuk L. Capillary electrophoresis in pharmaceutical

analysis: a survey on recent applications. J Chromatogr
Sci 2007;45(9):559-577.
241. Scriba GK. Fundamental aspects of chiral electromigration

techniques and application in pharmaceutical and
biomedical analysis. J Pharm Biomed Anal 2011, 55(4):688701.
228. Marsh A, Broderick M, Altria K, Power J, Donegan S, Clark

B. Capillary electrophoresis for pharmaceutical analysis.
Methods Mol Biol. 2008; 384:205-245.
229. Hendrickx A, Mangelings D, Heyden YV. Capillary methods
for drug analysis. J AOAC Int 2011 94(3):667-702.
242. Oliva DC, Vlez KT, Vzquez ALR. Pharmaceutical

formulations by capillary electrophoresis. J Mex Chem
Soc 2011, 55(2):79-83.
230. Mahuzier PE,Aurora Prado MS, Clark BJ, Kedor-Hackmann

ERM, Altria KD. An introduction to the theory and
application
of
microemulsion
electrokinetic
chromatography. LCGC Europe January 2003, pp1-6; http:/
/chromatographyonline.findanalytichem.com/lcgc/data/
articlestandard//lcgceurope/012003/42178/article.pdf.
243. Amin NC, Blanchin MD, Ak M, Fabre H. Capillary zone

electrophoresis as a potential technique for the
simultaneous determination of sulfadoxine and
pyrimethamine in tablet formulations. J Pharm Biomed Anal
2012;58;168-171.
231. Lunte SM, Radzik DM. Pharmaceutical & biomedical

applications of capillary electrophoresis. Elsevier, 1996.
244. Lunn G. Capillary electrophoresis methods for

pharmaceutical analysis, Wiley, New York, 2000.
232. Thormann W. Capillary electrophoretic separations.

Methods Biochem Anal 2011: 451-85.
245. Natishan TK. Recent pogress in the analysis of

pharmaceuticals by capillary electrophoresis. J Liq
Chromatogr R T 2005; 28(7-8): 1115-1160.
233. Thormann W. Capillary electrophoretic separations, in

protein purification: Principles, high resolution methods,
and applications, Third Edition (Janson JC ed.) John Wiley
& Sons, Inc., Hoboken, NJ, USA. Chapter 19, 2011.
doi: 10.1002/9780470939932.ch19.
246. Mohammadi I, Kanfer I, Walker RB. A capillary zone

electrophoresis (CZE) method for the determination of
cyclizine hydrochloride in tablets and suppositories. J
Pharm Biomed Anal 2004;35 (1):233-239.
247. Suntornsuk L, Capillary electrophoresis in pharmaceutical
analysis: A survey on recent applications. J Chromatogr
Sci 2007;45(9):559- 577.
234. Prokhorova AF , Shapovalova EN, Shpigun OA. Chiral

analysis of pharmaceuticals by capillary electrophoresis
using antibiotics as chiral selectors. J Pharm Biomed Anal
2010;53(5):1170-1179.
248. Suntornsuk L. Recent advances of capillary electrophoresis

in pharmaceutical analysis. Anal Bioanal Chem
2010;398(1):29-52.
235 Landers JP (ed.). Handbook of capillary and microchip

Eelectrophoresis and associated microtechniques, 3rd
Edition, CRC Press 2008.
249. Altria K, Marsh A, Snger-van de Griend C. Capillary

electrophoresis for the analysis of small-molecule
pharmaceuticals. Electrophoresis 2006; 27: 22632282.
236. Wolfgang T. Progress of capillary electrophoresis in

therapeutic drug monitoring and clinical and forensic
29
250. Haubitz M, Wittke S, Weissinger EM, Walden M, Rupprecht

HD, Floege J, et al. Urine protein patterns can serve as
diagnostic tools in patients with IgA nephropathy. Kidney
Inter 2005;67: 23132320;
263. Xie G, Su M, Li P, Gu X, Yan C, Qiu Y, et al. Analysis of

urinary metabolites for metabolomic study by pressurized
CEC. Electrophoresis. 2007; 28: 44594468.
264. Qu Q, Yan C. Pressurized capillary electrochromatographic
assay trimethoprim impurities using 1 um particle-based
columns. J Chromatogr A 2007; 1169: 228-234.
251. Yanyan D, Li J, Haiqing L, Da X. Comparison of on-line

concentration methods in capillary zone electrophoresis
for analysis of water-soluble vitamins. Anal Lett
2007;40(10): 2005 2015.
265. Li M, Zhou J, Gu X, Wang Y, Huang X, Yan C, Quantitative

capillary electrophoresis and its application in analysis of
alkaloids in tea, coffee, coca cola, and theophylline tablets.
J Sep Sci 2009; 32:267 274.
252. Zhang J, Konecny J, Glatz Z, Hoogmartens J, Schepdael

AV. Application of capillary electrophoresis in drug
metabolism studies. Curr Anal Chem 2007;3 (3):197-217.
266. Zhu H, Wu E, Chen J, Men C, Jang YS, Kang W, et al.

Enantioseparation and determination of sibutramine in
pharmaceutical formulations by capillary electrophoresis.
Bull Korean Chem Soc 2010;31(6):1496-1500.
253. Krishna MV, Srinath M, Sankar DG. Principles and

applications of capillary electrophoresis in new drug
discovery. Curr Trends Biotechnol Pharm 2008;2 (1):142155.
267. Nussbaumer S, Fleury-Souverain S, Rudaz S, Bonnabry P,

Veuthey JL. Determination of suxamethonium in a
pharmaceutical formulation by capillary electrophoresis
with contactless conductivity detection (CE-C4D). J Pharm
Biomed Anal 2009;49:333337.
254. Christophe Amin NC, Blanchin MD, Ak M, Fabre H.

Capillary zone electrophoresis as a potential technique for
the simultaneous determination of sulfadoxine and
pyrimethamine in tablet formulations. J Pharm Biomed Anal
2012:58:168-171.
268. Neubert RHH, Ruttinger HH (eds.). Affinity capillary

electrophoresis in pharmaceutics and biopharmaceutics.
Informa Healthcare 2003.
255. Yang X, Yuan H, Wang C, Su X, Hu L, Xiao D. Determination

of penicillamine in pharmaceuticals and human plasma by
capillary electrophoresis with in-column fiber optics lightemitting diode induced fluorescence detection. J Pharm
Biomed Anal 2007; 45(2):362-366.
269. Franzen U, Nguyen TTTN, Vermehren C, Gammelgaard B,

Ostergaard J. Characterization of a liposome-based
formulation of oxaliplatin using capillary electrophoresis:
encapsulation and leakage. J Pharm Biomed Anal. 2011;55
(1):16-22.
256. Anastos N, Barnett NW, Lewis WS. Capillary

electrophoresis for forensic drug analysis: A review. Talanta
2005;67: 269-279.
270. Abramski JK, Foteeva LS, Pawlak K, Timerbaev AR,

Jarosz M. A versatile approach for assaying in vitro
metallodrug metabolism using CE hyphenated with ICPMS. Analyst 2009;134 (10):1999-2002.
257. Hong W, Thompson RA. Capillary electrophoresis

technologies for screening in drug discovery. Drug Discov
Today: Technologies 2005;2:171-178.
258. Thanh PT, Hoogmartens J, Van Schepdael A. Recent
advances in pharmaceutical applications of chiral capillary
electrophoresis. J Pharm Biomed Anal 2006;41;1-11.
271. Giuffrida A, Contino AG, Messina M, Cucinotta V. Mass

spectrometry detection as an innovative and
advantageous tool in ligand exchange capillary
electrophoresis. Electrophoresis 2011;32 (10):1176-1181.
259. Mayolo-Deloisa K , Gonzalez-Valdez J, Guajardo-Flores

D, Aguilar O, Benavides J, Rito-Palomares M. Current
advances in the non-chromatographic fractionation and
haracterization of PEGylated proteins. J Chem Technol
Biotechnol 2010; 86(1):18-25.
272. Brunner LJ, DiPiro JT, Feldman S. High-performance

capillary electrophoresis in the pharmaceutical sciences.
Pharmacotherapy 1995;15(1):1-22.
273. Lomsadze K, Martinez-Giron AB, Castro-Puyana M,
Chankvetadze I, Grego AL, A. Salgado A, et al. About the
role of enantioselective selectorselectand interactions and
the mobilities of diastereomeric associates in enantiomer
separations using CE. Electrophoresis 2009;30:2803-2822.
260. Lin YH, Wu SM. Analysis of omeprazole and lansoprazole

in capsules by capillary zone electrophoresis. LCGC
Europe, LCGC Europe, Mar 1, 2005.
261. Patterson BM, Danielson ND, Sommer AJ. Attenuated total
internal reflectance infrared microspectroscopy as a
detection technique for capillary electrophoresis Anal
Chem 2004;76: 38263832.
274. Lee DC, Webb M. Pharmaceuticals Analysis. Wiley-India,

2008.
275. Schmitt-Kopplin P. Capillary electrophoresis: methods and
protocols. Humana Press, 2008.
262. Huo Y, Kok WT. Recent applications in CEC.

Electrophoresis. 2008; 29(1): 44594468.
30
276. Yoon S, Kim J, Hum J, Kim H, Park S, Kladwang W, et al.

HiTRACE: high-throughput robust analysis for capillary
electrophoresis. Bioinformatics 2011; 27(13): 1798-1805.
288. Injac R, Koevar N, trukelj B. Optimized method for

determination of amoxicillin, ampicillin, sulfamethoxazole,
and sulfacetamide in animal feed by micellar electrokinetic
capillary chromatography and comparison with highperformance liquid chromatography. Croat Chem Acta
2009;82(3):685694.
277. Liu C, Kane TE, Li Q. Automated parallel capillary

electrophoresis system with hydrodynamic sample
injection. 09/15/2011, 20110220508; http://www.faqs.org/
patents/app/20110220508#ixzz1b1bEZ9Xy
289. Wang X, Zeng S. Stereoselective metabolic and

pharmacokinetic analysis of the chiral active components
from herbal medicines. Curr Pharm Anal 2010; 6(1):39-52.
278. Yu T, Du Y, Chen B. Evaluation of clarithromycin

lactobionate as a novel chiral selector for enantiomeric
separation of basic drugs in capillary electrophoresis.
Electrophoresis 2011;32: 18981905.
290. Dami M, Nigovi B. Fast analysis of statins in

pharmaceuticals by MEKC. Chromatographia 2010; 71(34): 233-240.
279. Servais AC, Rousseau A, Fillet M, Lomsadze K, Salgado

A, Crommen J, et al. Separation of propranolol enantiomers
by CE using sulfated beta-CD derivatives in aqueous and
non-aqueous electrolytes: comparative CE and NMR study.
Electrophoresis 2010, 31, 1467-1474.
291 Silva CA, Aurora-Prado MS, Altria KD, Tavares MFM.

Separation of steroids and the determination of estradiol
content in transdermic patches by microemulsion
electrokinetic chromatography. Chromatographia 2011; 73:
373-378.
280. Lemma T, Pawliszyn J. Human serum albumin interaction

with oxaliplatin studied by capillary isoelectric focusing
with the whole column imaging detection and
spectroscopic method. J Pharma Biomed Anal 2009; 50(4):
570-575.
292. Borst C, Holzgrabe U. Comparison of chiral electrophoretic

separation methods for phenethylamines and application
on impurity analysis. J Pharm Biomed Anal 2010;53:12011209.
281. Zhan Y, Lemma T, Musteata FM, Pawliszyn J. Development

of a simple ampholyte-free isoelectric focusing slab
electrophoresis for protein fractionation. J Chromatogr A
2009;1216 (14);2928-2933.
293. Snchez-Hernndez L, Crego AL, Marina ML, Garca-Ruiz

C. Sensitive chiral analysis by CE: An update.
282. Palm A. Peptides, Proteins, and Antibodies: Capillary

Isoelectric Focusing. Encyclopedia of chromatography,
Third Edition, Taylor and Francis, 2009.
294. Snchez-Hernndez L, Garca-Ruiz C, Luisa Marina M,

Luis Crego A. Recent approaches for enhancing sensitivity
in enantioseparations by CE. Electrophoresis 2010;31:28
43.
283. Chang CL, Leong JC, Hong TF, Wang YN, Fu LM.
Experimental and numerical analysis of high-resolution
injection technique for capillary electrophoresis microchip.
Int J Mol Sci 2011; 12(6): 35943605.
295. Zandkarimi M, Shafaati A, Foroutan SM. Chiral separation

of basic and zwitterionic electrophoresis highly sulfated
cyclodextrins using short-end injection capillary
electrophoresis. Iran J Pharm Res 2008;7(4):275-281.
284. Kustos I, Kocsis B, Kilr F. Bacterial outer membrane

protein analysis by electrophoresis and microchip
technology. Expert Rev Proteomics 2007;4(1):91-106.
296. Hongjun E, Su P, Farooq MU, Yang Y. Microwave-assisted

preparation of a -cyclodextrin-based stationary phase for
open tubular capillary electrochromatography. Anal Lett
2010;43(15): 2372-2380.
285. Van Eeckhaut A, Yvette Michott Y (eds.) Chiral separations

by capillary electrophoresis, 2009.
297. Elbashir AA, Aboul-Enein HY. Applications of capillary

electrophoresis with capacitively coupled contactless
conductivity detection (CE-C4D) in pharmaceutical and
biological analysis. Biomed Chromatogr BMC 2010; 24(10):
1038-1044.
286. Rossella Gottardo a, Federica Bortolotti a, Giorgia De Paoli

a, Jennifer Paola Pascali a, Ivan Miks"k b, Franco Tagliaro.
Hair analysis for illicit drugs by using capillary zone
electrophoresis-electrospray ionization-ion trap mass
spectrometry. J Chromatogr A 2007;1159:185189.
Morzunova TG. Capillary electrophoresis in pharmaceutical
analysis. Pharm Chem J 2006; 40(3):158-170.
298. Al Azzam KM, Saad B, Aboul-Enein HY. Simultaneous

determination of atenolol and amiloride in pharmaceutical
preparations by capillary zone electrophoresis with
capacitively coupled contactless conductivity detection.
Biomed chromatogr BMC 2010;24(9): 948-953.
287. Desiderio C, Valeria Rossetti D, Perri F, Giardina B, Messana

I, Castagnola M. Enantiomeric separation of baclofen by
capillary electrophoresis tandem mass spectrometry with
sulfobutylether--cyclodextrin as chiral selector in partial
filling mode. J Chromatogr B 2008;875(1): 280-287.
299. Fracassi Da Silva JA, Vitorazzi De Castro N, Pereira De

Jesus D, Faria AF, De Souza MVN, Leal De Oliveira MA.
Fast determination of ethambutol in pharmaceutical
31
formulations using capillary electrophoresis with

capacitively coupled contactless conductivity detection.
Electrophoresis 2010; 31(3):570-574.
310. Terabe S. Micellar electrokinetic chromatography for highperformance analytical separation. Chem Rec 2008;8:291301.
300. Silva Felix F, Lucio Do Lago C, Angnes L. Determination of

ciclopirox olamine in pharmaceutical products by capillary
conductivity detection. Electrophoresis 2011;32(8):900-905.
311. Fan LY, Chen HL, Chen XG, Hu ZD. Separation and
determination of sulfonamides in pharmaceutical
preparations by a microfluidic capillary electrophoresis
system with a continuous sample introduction interface. J
Sep Sci 2003;26:13761382.
301. Doan TKO, Kub P, Kub P, Kiplagat IK, Boek P.

Analysis of inorganic cations in biological samples by the
combination of micro-electrodialysis and capillary
conductivity detection. Electrophoresis 2011;32(3-4):464471.
312. Gavina JMA, Britz-McKibbin P. Protein unfolding and

conformational studies by capillary electrophoresis. Curr
Anal Chem 2007;3:17-31.
313. Fan B, Stewart JT. Determination of lamivudine /didanosine
/saquinavir in human serum using capillary zone
electrophoresis. J Liq Chromatogr R T 2002;25(2):241249.
302. Otieno AC, Mwongela SM. Capillary electrophoresis-based

methods for the determination of lipids -A review. Anal
Chim Acta 2008;624:163174.
314. Fan B, Stewart JT. Determination of stavudine/didanosine/

saquinavir and stavudine /didanosine /efavirenz in human
serum by micellar electrokinetic chromatography (MEKC).
J Liq Chromatogr R T 2002;25(6): 937947.
303. Wiedmer SK. Interactions between analytes and lipid

biomembranes by capillary electromigration techniques.
Mini-symposium: Characterization of drugs and related
compounds using capillary-based techniques Monday,
October 10, 2011 in Benzon Auditorium Faculty of
Pharmaceutical Sciences, University of Copenhagen,
Universitetsparken 2, 2100, Copenhagen.
315 Fan B, Stewart JT. Determinations of zidovudine/

didanosine/nevirapine and zidovudine/didanosine/
ritonavir in human serum by micellar electrokinetic
chromatography. J Pharm Biomed Anal 2002;30(4):955960.
316. Driouich R, Takayanagi T, Oshima M, Motomizu S.
Separation and determination of haloperidol, parabens and
some of their degradation products by micellar
electrokinetic chromatography. J Chromatogr A 2000;903:
271-278
304. Geiser L, Veuthey JL. Nonaqueous capillary electrophoresis

in pharmaceutical analysis. Electrophoresis 2007; 28(12):45-57.
305. Gomez MR, Olsina RA, Martnez LD, Silva MF.
Simultaneous determination of cloramphenicol, salicylic
acid and resorcinol by capillary zone electrophoresis and
its application to pharmaceutical dosage forms. Talanta
2003;61(2):233-238.
317. Elbashir A, Saad B, Ali ASM. Capillary electrophoresis

methods for pharmaceuitcal Analysis. LAP Lambert
Academic Publishing, 2010.
318. Chiang JF, Hsiao YT, Ko WK, Wu SM. Analysis of multiple
abused drugs and hypnotics in urine by sweeping CE.
306. Lechnou CN. Capillary electrophoresis used as an

alternative to HPLC for pharmaceutical analysis of
antifungal agents. Thomas Jefferson University, 2008.
Master s Theses & Dissertations. Paper 1. http://
jdc.jefferson.edu/diss_masters/1
319. Jinno K, Han Y, Nakamura M. Analysis of anxiolytic drugs

by capillary electrophoresis with bare and coated
capillaries. J Capillary ElectroP. 1996 ;3(3):139-145.
307. Gbitz G, Schmid MG. Recent advances in chiral separation

principles in capillary electrophoresis and capillary
electrochromatography. Electrophoresis 2004;23: 3981
3996.
320. Baldacci A, Theurillat R, Caslavska J, Pardubsk H,

Brenneisen R, Thormann W, Determination of gammahydroxybutyric acid in human urine by capillary
electrophoresis with indirect UV detection and
confirmation with electrospray ionization ion-trap mass
spectrometry. J Chromatogr A 2003; 990: 99-110.
308. Lewis A, Cranny A, Green N, Harris N, Stokes K, Wharton

J, et al. A closed-loop, non-linear, miniaturised capillary
electrophoresis system enabled by control of
electroosmotic flow. In: The 15th International Symposium
on field- and flow-based separations (FFF 2011), 23/05/
11 - 25/05/11, San Francisco.
321. Gong XY, Kubn P, Scholer A, Hauser PC. Determination

of gamma-hydroxybutyric acid in clinical samples using
capillary electrophoresis with contactless conductivity
detection. J Chromatogr A 2008; 1213:100-104.
309. Terabe S. In Micellar electrokinetic chromatography,

Handbook of capillary and microchip electrophoresis and
associated microtechniques, 3rd Ed. 2008; 2008:109-133.
322. Bishop SC, Lerch M, McCord BR. Micellar electrokinetic

chromatographic screening method for common sexual
32
assault drugs administered in beverages. Forensic Sci Int.

2004; 141: 7-15.
335. Kamoda S, Ishikawa R, Kakehi K. Capillary electrophoresis

with laser-induced fluorescence detection for detailed
studies on N-linked oligosaccharide profile of therapeutic
recombinant monoclonal antibodies. J Chromatogr A
2006;1133(1-2):332-339.
323. Lewis ML, Engle LJ, Pierceall WE, Hughes DE, Shaw KJJ.
Affinity capillary electrophoresis for the screening of novel
antimicrobial targets. J Biomol Screen 2004;4:303-308.
336. Silvertand LHH, Torao JS, van Bennekom WP, de Jong

GJ. Recent developments in capillary isoelectric focusing.
J Chromatogr A 2008;1204(2):157-170.
324. Belenky A, Hughes D, Korneev A, Dunayevskiy Y. Capillary

electrophoretic approach to screen for enzyme inhibitors
in natural extracts. J Chromatography A 2004;1053:247251.
337. Wei J, Gu X, Wang Y, Wu Y, Yan C. Two-dimensional

separation system by on-line hyphenation of capillary
isoelectric focusing with pressurized capillary
electrochromatography for peptide and protein mapping.
325. Pierceall WE, Zhang L, Hughes DE, Fu H. (eds.). Affinity

capillary electrophoresis analyses of protein-protein
interactions in target-directed drug discovery. Humana
Press, 2004.
338. Little MJ, Paquette DM, Roos PK. Electrophoresis of

pharmaceutical proteins: status quo. Electrophoresis
2006;27:2477-2485.
326. Neubert R, Rttinger HH (eds.). Affinity capillary

Marcel Dekker, 2003.
339. Que AH, He XZ, Toal MM, Cook KS. Capillary

electrophoresis in the biopharmaceutical industry of
monoclonal antibodies. Abstracts of Papers, 231st ACS
National Meeting, Atlanta, GA, United States, March 2630, 2006, ANYL-037.
327. Mironov GG, Chechik AV, Ozer R, Bell JC, Berezovski MV.
Viral quantitative capillary electrophoresis for counting
intact viruses. Anal Chem 2011; 83 (13):5431-5435.
328. Elbashir AA, Aboul-Enein HY. Applications of capillary
conductivity detection (CE-C4D) in pharmaceutical and
biological analysis. Biomed Chromatogr 2010;24(10):10381044.
340. Rochu D, Masson P. Capillary electrophoresis for

monitoring stability of pharmaceutical proteins. Ann Pharm
Fr 2003;61:185-195.
341. Rodriguez-Diaz R, Tuck S, Ng R, Haycock F, Wehr T, Zhu
M. Capillary electrophoresis of biopharmaceutical proteins.
Anal Tech Biopharm Dev 2005;161-226.
329. Hunt G, Nashabeh W. Capillary electrophoresis sodium

dodecyl sulfate nongel sieving analysis of a therapeutic
recombinant monoclonal antibody: A biotechnology
perspective. Anal Chem 1999;71:2390-2397.
342. Salas-Solano O. Capillary electrophoresis in biotechnology:

A practical tool to analyze and characterize therapeutic
proteins. Abstract of Papers, 238th ACS National Meeting,
Washington, DC, United States, August 16-20, 2009 2009,
BIOT-319.
330. Jouyban A, Kenndler E, Impurity analysis of

pharmaceuticals using capillary electromigration methods.
331. Racaityte K, Kiessig S, Kalman F. Application of capillary
zone electrophoresis and reversed-phase high-performance
liquid chromatography in the biopharmaceutical industry
for the quantitative analysis of the monosaccharides
released from a highly glycosylated therapeutic protein. J
Chromatogr A 2005;1079:354-365.
343. Jensen H. Flow Induced Dispersion Analysis: A new

approach to non-covalent interactions and instant elisa.
Mini-symposium: Characterization of drugs and related
compounds using capillary-based techniques,
Monday, October 10, 2011 in the Benzon Auditorium, The
Faculty of Pharmaceutical Sciences, Universitetsparken 2,
2100 Copenhagen. http://www.farma.ku.dk/fileadmin/DRA/
2011/Programme_characterization_of_drugs
_J%C3%98_10_oktober.pdf
332. Bosserhoff A, Hellerbrand C. Capillary Electrophoresis.

Chapter 7. In: Molecular diagnostics, Patrinos and Ansorge,
Elsevier, Inc, 2005.
344. Kamoda S, Kakehi K. Capillary electrophoresis for the

analysis of glycoprotein pharmaceuticals. Electrophoresis
2006;27(12):2495-504.
333. https://www.beckmancoulter.com/wsrportal/wsr/researchand-discovery/products-and-services/capillaryelectrophoresis/protein-characterization-applications/
index.htm.
345. Zhang J, Chakraborty U, Villalobos AP, Brown JM, Foley

JP. Optimization and qualification of capillary zone
electrophoresis method for glycoprotein isoform
distribution of erythropoietin for quality control laboratory.
J Pharm Biomed Anal 2009;50:538-543.
334. Zhang J. Quantitative biopharmaceutical applications of

capillary electrophoresis. http://hdl.handle.net/1860/3166.
33
346. Righetti PG. Capillary electrophoresis in analytical

biotechnology. CRC Press, 1996.
357. Lu H, Yuan G, He Q, Chen H. Rapid analysis of anthracycline

antibiotics doxorubicin and daunorubicin by microchip
capillary electrophoresis. Microchem J 2009 ; 92(2) : 170173.
347. Wong PK, Wang TH, Deval JH, Ho CM. Electrokinetics in

micro devices for biotechnology applications.
Mechatronics IEEE/ASME Transactions on 2004; 9(2):
366 376.
358. Kostal V, Katzenmeyer J, Arriaga EA. Capillary

electrophoresis in bioanalysis. Anal Chem 2008; 80(12):
45334550.
348. Lagu AL Applications of capillary electrophoresis in

biotechnology. Electrophoresis 1999;20(15-16):3145-55.
359. Suresh Babu CV, Gudihal R, Preckel T, Greiner M.

Application of Capillary Electrophoresis-Mass
Spectrometry in Biopharmaceuticals: Glycopeptide
Analysis of Monoclonal Antibodies. CE-Pharm 2010, P108.
349. USP Chapter in USP Second supplement USPNF, 2896

2900 (2000); Pharmeuropa 1999;112: 411412.
350. Guidance for Industry: Q4B Evaluation and
Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions, Annex 11 Capillary Electrophoresis General
Chapter: U. S. Department of Health and Human Services
Food and Drug Administration Center for Drug Evaluation
and Research (CDER) Center for Biologics Evaluation and
Research (CBER) September 2010 ICH; http://
w w w. f d a . g o v / d o w n l o a d s / D r u g s /
GuidanceComplianceRegulatoryInformation/Guidances/
UCM194492.pdf ; European Pharmacopoeia (Ph. Eur.):
Supplement 6.6 (published June 2009, and official January
1, 2010), Capillary Electrophoresis :
http://www.std.pmda.go.jp/jpPUB/Data/ENG/jpdata/
H201105_jp15_errata.pdf on May 28, 2010. ;United States
Pharmacopeia (USP): <1053> Biotechnology-derived
Articles Capillary Electrophoresis, USP Revision Bulletin
posted May 29, 2009, official July 1, 2009.
360. Kartsova L, Alekseeva A. Ligand-exchange capillary

electrophoresis. J Anal Chem 2011;66(7):563-571.
361. Lagu AL. Applications of capillary electrophoresis in
biotechnology. Electrophoresis. 1999;20(15-16):3145-3155.
362. Szabo Z, Guttman A, Rejtar T, Karger BL. Improved sample
preparation method for glycan analysis of glycoproteins
by CE-LIF and CE-MS, Electrophoresis 2010 ;31 : 1389-95.
363. Chen AB, Nashabeh W, Wehr T (Eds.), CE in
Biotechnology: Practical applications for protein and
peptide analyses, Chromatographia CE Series: Altria KD
(ed.), Supplement Vol. 53, Vieweg Publishing, Wiesbaden,
2001.
364. Scriba GKE, Psurek A. Separation of peptides by capillary
electrophoresis. In: Capillary electrophoresis : Methods
and protocols, Series: Methods Mol Biol 2008;384:483-506.
351. Text on validation of analytical procedures: methodology.

International conference on harmonization of technical
requirements for the registration of pharmaceuticals for
human use (ICH), IFPMA Ed., (Geneva, Switzerland, 1996).
365. Nicola V (ed.) Capillary electrophoresis of carbohydrates:

From monosaccharides to complex polysaccharides,
Springer, 1st Edition, 2011.
352. Fabre H, Altria KD. Validating CE methods for

pharmaceutical analysis. LC GC Europe CE Currents, May
2001, pp 1-5.
366. Alahmad Y, Tran NT, Taverna M. Analysis of intact

glycoprotein biopharmaceuticals by capillary
electrophoresis. Capillary ElectroP Carbohyd 2011;173-204.
353. Hu Q, Hu G, Zhou T, Fang Y. Determination of dissociation

constants of anthrocycline by capillary zone
electrophoresis with amperometric detection, J Pharm
Biomed Anal 2003;31(4): 679-684.
367. Petersen J, Baker D, Dibya D, Varineau P, Kenseth J. Recent

application developments in genomic research using the
AdvanCE FS capillary electrophoresis platform. BMC
Proc 2011;5(Suppl 7):P50.
354. Hu Q, Zhou T, Zhang L, Li H, Fang Y. Determination of

idarubicin in human urine by capillary zone electrophoresis
with amperometric detection. Fresen J Anal Chem
2000;368(8):844-847.
368. Nakano M, Higo D, Arai E, Nakagawa T, Kakehi K, Taniguchi

N, et al. Capillary electrophoresis-electrospray ionization
mass spectrometry for rapid and sensitive N-glycan analysis
of glycoproteins as 9-fluorenylmethyl derivatives.
Glycobiology 2009 ;19(2):135-143.
355. Hu Q, Zhou T, Hu G, Fang Y. Determination of sugars in

Chinese traditional drugs by CE with amperometric
detection, J Pharm Biomed Anal 2002;30:1047-1053.
369. Ahuja S. Chiral separation methods for pharmaceutical and

biotechnological products. John Wiley and Sons, 2010.
356. Hu Q, Zhang L, Zhou T, Fang Y. Determination of

daunorubicin in human urine by capillary zone
electrophoresis with amperometric detection. Anal Chim
Acta 2000;416:15-19.
370. Nunnally B, Park SS, Patel K, Hong M, Zhang X, Wang SX,

et al. A series of collaborations between various
pharmaceutical companies and regulatory authorities
34
concerning the analysis of biomolecules using capillary

electrophoresis. Chromatographia 2006;64(5-6):359-368.
drug formulation using capillary electrophoresis.

371. Ryan N, Lantz, Andrew L. Capillary electrophoresis based

microbial detection and separation (2009). Student
Summer Scholars. Paper 36. http://scholarworks.gvsu.edu/
sss/36.
383. Franzen U, Vermehren C, Jensen H, stergaard J.

Physicochemical characterization of a pegylated liposomal
drug formulation using capillary electrophoresis.
Electrophoresis 2011;32:111.
372. Kailasa SK, Kang, SH. Microchip-based capillary

electrophoresis for DNA analysis in modern
biotechnology: A review. Sep Purif Rev 2009;38(3):242288.
384. Imee G. Arcibal, Michael F. Santillo, Ewing AG. Recent

advances in capillary electrophoretic analysis of individual
cells. Anal Bioanal Chem 2007;387(1): 5157.
385. Oh MH, Cox JM. Quantitative analysis of the bacillus
cereus emetic toxin, cereulide, using micellar electrokinetic
chromatography capillary electrophoresis. J Food Safety
2010;30(3):652.
373. Gu X, Chu Q, ODwyer M, Zeece M. Analysis of resveratrol

in wine by capillary electrophoresis. J Chromatogr A
2000;881:471-481.
374. Moini M, Klauenberg K, Ballard M. Dating silk by capillary
electrophoresis mass spectrometry. Anal Chem 2011;
83(19):7577-7581.
386. Liu X, Gomez FA. Frontal analysis microchip capillary

electrophoresis to study the binding of ligands to receptors
derivatized on magnetic beads. Anal Bioanal Chem
2009;393(2):615.
375. Gamze Kavran B; Stefan S. Direct determination of native

proteins in miniaturized capillary electrophoresis system.
J Nanosci Nanotechnol 2009;9(4):2645-2650.
387. Wang H, Zhang D, Wang Z etc .Methodology of capillary

electrophoresis-laser induced fluorescence immunoassay
for highly sensitive detection of DNA adducts. Chin J
Chromatogr 2009;27(5): 642-647.
376. Knjazeva T, Kaljurand M. Capillary electrophoresis frontal

analysis for the study of flavonoid interactions with human
serum albumin. Anal Bioanal Chem 2010;397(6): 2211-2219.
388. Vrouwe EX . Quantitative microchip capillary

electrophoresis for inorganic ion analysis at the point of
care. Ph D Dissertation, University of Twente, The
Netherlands. 2005.
377. stergaard J, Heegaard NHH. Capillary electrophoresis

frontal analysis: Principles and applications for the study
of drug-plasma protein binding. Electrophoresis 2003; 24:
29032913.
389. Khandurina J, Blum DL, Guttman A. Automated

carbohydrate profiling by capillary electrophoresis: A
bioindustrial approach. Electrophoresis 2004;25: 2326.
378. Shibukawa A, Yoshimoto Y, Ohara T, Nakagawa T. Highperformance capillary electrophoresis/frontal analysis for
the study of protein binding of a basic drug. J Pharm Sci
1994;83(5):616-9
390. Radko SP, Chrambach A: Separation and characterization

of sub-mu m- and mu m-sized particles by capillary zone
electrophoresis. Electrophoresis 2002; 23:1957-1972.
379. Vuignier K, Schappler J, Veuthey JL, Carrupt PA, Martel S.

Improvement of a capillary electrophoresis/frontal analysis
(CE/FA) method for determining binding constants:
discussion on relevant parameters. J Pharm Biomed Anal
2010;53(5):1288-1297.
391. Quang C, Petersen SL, Ducatte GR, Ballou NE, et al.:

Characterization and separation of inorganic fine particles
by capillary electrophoresis with an indifferent electrolyte
system. J Chromatogr A 1996;732:377-384.
380. Fu SP, Xiao Zhang Z, Zhang F, Qing XU, Hong Bin XIAO,
Xin Miao LIANG. Study on the Interaction between
Strychnine and Bovine Serum Albumin by Capillary
Electrophoretic Frontal Analysis. Chin Chem Lett 2005;16
(9):1233-1236.
392. Vanifatova NG, Spivakov BY, Mattusch J, Spivakov BYa,

Vanifatova NG: Investigation of iron oxide nanoparticles
by capillary zone electrophoresis. Talanta 2005;66:605-610.
393. Liu FK, Ko FH, Huang PW, Wu CH, Chu TC: Studying the
size/shape separation and optical properties of silver
nanoparticles by capillary electrophoresis. J Chromatogr
A 2005;1062:139-145.
381. Franzen U, Jorgensen L, Larsen C, Heegaard NHH,

stergaard J. Determination of liposomebuffer
distribution coefficients of charged drugs by capillary
electrophoresis frontal analysis. Electrophoresis
2009;30: 27112719.
394. Liu FK, Lin YY, Wu CH: Highly efficient approach for
characterizing nanometer-sized gold particles by capillary
electrophoresis. Anal Chim Acta 2005;528:249-254.
382. Franzen U, Vermehren C, Jensen H, stergaard J.

Physicochemical characterization of a PEGylated liposomal
395. Song X, Li L, Qian H, Fang N, Ren J: Highly efficient size

separation of CdTe quantum dots by capillary gel
35
electrophoresis using polymer solution as sieving medium.

403. Jackman R, Schmerr MJ. Analysis of the performance of

antibody capture methods using fluorescent peptides with
capillary zone electrophoresis with laser-induced
fluorescence. Electrophoresis 2003;24:892-896.
396. Huang XY, Weng JF, Sang FM, Song X, Cao C, Ren J.
Characterization of quantum dot bioconjugates by capillary
electrophoresis with laser-induced fluorescent detection.
J Chromatogr A 2006;1113:251-254.
404. Yang WC, Schmerr MJ, Jackman R, Bodemer W, Yeung ES.

Capillary electrophoresis-based noncompetitive
immunoassay for the prion protein using fluoresceinlabeled protein a as a fluorescent probe. Anal Chem
2005;77:4489-4494.
397. Weng J, Song X, Li L, Qian H, Chen K, Xu X, et al. Highly

luminescent CdTe quantum dots prepared in aqueous
phase as an alternative fluorescent probe for cell imaging.
Talanta 2006;70:397-402.
398. Feng HT, Law WS, Yu LJ, Li SFY. Immunoassay by capillary
electrophoresis with quantum dots. J Chromatogr A
2007;1156:75-79.
405. Yang WC, Yeung ES, Schmerr MJ. Detection of prion

protein using a capillary electrophoresis-based competitive
immunoassay with laser-induced fluorescence detection
and cyclodextrin-aided separation. Electrophoresis
2005;26:1751-1759.
399. Schmerr MJ, Goodwin KR, Cutlip RC. Capillary

electrophorsis of the scrapie prion protein from sheep brain.
J Chromatogr A 1994; 680:447-453.
406. Vicente G, Colon LA. Separation of bioconjugated quantum

dots using capillary electrophoresis. Anal Chem
2008;80:1988-1994.
400. Schmerr MJ, Goodwin KR, Cutlip RC, Jenny AL.

Improvements in a competition assay to detect scrapie
prion protein by capillary electrophoresis. J Chromatogr
B 1996;681:29-35.
407. Pereira M, Lai EPC. Capillary electrophoresis for the

characterization of quantum dots after non-selective or
selective bioconjugation with antibodies for immunoassay.
J Nanobiotechnol 2008;6:10 doi:10.1186/1477-3155-6-10.
401. Schmerr MJ, Jenny A: A diagnostic test for scrapie-infected

sheep using a capillary electrophoresis immunoassay with
fluorescent-labeled peptides. Electrophoresis 1998;19:409414.
408. Pereira M, Lai EPC, Hollebone B. Characterization of

quantum dots using capillary zone electrophoresis.
409. Shiddiky MJA, Shim YB. Microchip and capillary
electrophoresis using nanoparticles . In: Kumar CSSR.
Microfluidic devices in nanotechnology: Applications.
John Wiley and Sons, Hoboken, N.J., U.S., Wiley, 2010, pp.
213-253.
402. Schmerr MJ, Jenny A, Bulgin MS, Miller J, Randall C,

Kathryn G. Use of capillary electrophoresis and fluorescent
labeled peptides to detect the abnormal prion protein in
the blood of animals that are infected with a transmissible
spongiform encephalopathy. J Chromatogr A 1999;853:207214.
36

An Overview of Capillary Electrophoresis Pharmaceutical Biopharmaceutical and Biotechnology Applicat PDF

Încărcat de

Informații document

Descriere originală:

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

An Overview of Capillary Electrophoresis Pharmaceutical Biopharmaceutical and Biotechnology Applicat PDF

Încărcat de

Drepturi de autor:

Formate disponibile

J Pharm Educ Res Vol. 2, Issue No.

An overview of capillary electrophoresis: Pharmaceutical,

Received: November 08, 2011; Accepted: November 30, 2011

dimensions of the capillaries greatly increased the surface

Electrophoresis is the migration of ions or solutes

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

First high voltage CE system (with rotating 3 mm internal diameter capillaries.

Isoelectric focussing was introduced in capillary format

Micellar electrokinetic chromatography, a hybrid of electrophoresis and chromatography was introduced by

Anionic micelles were used as a pseudostationary phase to separate neutral compounds.

Grossman expands work with sieving polymers.

High-resolution CE provides an alternative for rapid identification of Mycobacterium species.

An overview over quantitative measurements performed by CE-MS.

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

Advantages over HPLC

/Capillary electrochromatography (CEC)

Qualities of CE such as high efficiency of separation,

Micellar electrokinetic chromatography (MEKC)

Microemulsion electrokinetic chromatography

Capillary isoelectric focusing (CIEF)

Capillary isotachophoresis (CITP)

Pressurized capillary electrochromatography

Affinity capillary electrophoresis (ACE)

Imunoaffinity capillary electrophoresis (IACE)

Nano capillary electrophoresis (NCE)

Microchip-based capillary electrophoresis

Various separation modes of CE

In CZE, analytes move in the electroosmotic flow

xiv) Microfluidic capillary electrophoresis (MFCE)

The differential movement for migration of ions by

Capillary zone electrophoresis (CZE)

Nonaqueous capillary electrophoresis (NACE)

Capillary gel electrophoresis (CGE)

Capilliary electrokinetic chromatography (CEKC)

Capillary zone electrophoresis (CZE)

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

biological macromolecules such as oligonucleotides, DNA

ultimately on the differences in analytes electrophoretic

iii) Capillary gel electrophoresis (CGE)

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

proteins. Scientists demonstrated the SDS washing bound

and have been used for pharmaceutical applications

CGE can be used as an accurate and high throughput

v) Micellar electrokinetic capillary chromatography

Capillary electrochromatography (CEC)

MEKC can be employed to separate both charged

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

separation of various hydrophobic and hydrophilic

surfactants, organic modifiers, temperature and variable

vii) Capillary isoelectric focusing (CIEF)

MEEKC is an electrodriven separation technique in

Besides performing conventional CIEF, a method

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

pepsin with pIs higher than 10 or below 3 were separated

separation was developed for the separation and

viii) Capillary Isotachophoresis (CITP)

x) Affinity capillary electrophoresis (ACE)

Cyclodextrin-mediated CITP in cationic regime of the

J Pharm Educ Res Vol. 2, Issue No. 2, December 2011

of materials, and the enzymatic reactions for analytical

successfully used to examine protein-drug, protein-DNA,

A nanocapillary electrophoretic electrochemical