Critical Reviews in Analytical Chemistry

ISSN: 1040-8347 (Print) 1547-6510 (Online) Journal homepage: https://www.tandfonline.com/loi/batc20

Linezolid—A Review of Analytical Methods in

Pharmaceuticals and Biological Matrices

K. S. Kokilambigai, K. S. Lakshmi, A. Sai Susmitha, R. Seetharaman & J.

Kavitha

To cite this article: K. S. Kokilambigai, K. S. Lakshmi, A. Sai Susmitha, R. Seetharaman & J.

Kavitha (2019): Linezolid—A Review of Analytical Methods in Pharmaceuticals and Biological
Matrices, Critical Reviews in Analytical Chemistry, DOI: 10.1080/10408347.2019.1599709

To link to this article: https://doi.org/10.1080/10408347.2019.1599709

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CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY
https://doi.org/10.1080/10408347.2019.1599709

Linezolid—A Review of Analytical Methods in Pharmaceuticals and

Biological Matrices
K. S. Kokilambigai, K. S. Lakshmi, A. Sai Susmitha, R. Seetharaman, and J. Kavitha
Department of Pharmaceutical Analysis, SRM College of Pharmacy, SRM Institute of Science and Technology, Kancheepuram, Tamil Nadu, India

ABSTRACT KEYWORDS
Bacterial resistance to antibiotics is a growing phenomenon in the world. Considering the rele- Bioanalytical methods;
vance of antimicrobials for population and the reduction in the registration of new antimicrobials chromatographic methods;
by regulatory agencies, proper quality control is required to minimize the spread of bacterial Linezolid; review;
spectrophotometry
resistance and ensure the effectiveness of a treatment, as well as safety for the patient. The recent
addition to the antimicrobial world is the oxazolidinone classes of antibiotics, especially useful to
treat infections caused by Gram-positive bacteria. Eperezolid and linezolid (LIN) are the two mem-
bers of the oxazolidinone class of antibiotics. LIN was the first oxazolidinone approved by the
Food and Drug Administration. The present review focuses on the analytical methods for the
assessment of LIN in pharmaceuticals and biological matrices. The critical validation parameters
like the linearity, limit of detection, limit of quantification are discussed for the individual method.
Also the critical quality attributes like the sensitivity and the sample preparation techniques for
bioanalytical methods are also discussed. Furthermore, some future trends that can be incorpo-
rated in the determination of similar drugs are also suggested.

1. Introduction LIN, the class of antimicrobial drug having oxazolidinone

Gram-positive pathogens play a significant cause of morbid-
ity and mortality in both community and health care set-
tings. Traditionally, glycopeptides are the antibiotics of
preference for multiresistant gram-positive pathogens but
there is obstacle with their use, including the emergence of
glucopeptide-resistant strains, tissue penetration, accom-
plishing and monitoring adequate serum levels. Newer anti-
biotics such as linezolid (LIN), a synthetic oxazolidinone,
are available for the treatment of resistant Gram-positive
bacterial infections since 2000.[1]
LIN is the 1st member of new class of synthetic anti-
microbial agents “oxazolidinones.” It is useful in the treat-
ment of resistant gram-positive coccal and bacillary
infection. It acts by inhibiting bacterial protein synthesis at
an early stage and a site difference from that of other anti-
microbial agents. It binds with 23S fraction (p-site) of the
50 S ribosome and interferes in the production of ternary
N-formyl methionine-tRNA-70S initiation complex. It is
used as an antibacterial.[2] LIN is chemically, N-[(5S)-3-[3-
fluoro-4-[4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]me-
thyl]acetamide (Figure 1). The molecular formula is
C16H20FN3O4 and has a molecular mass of about 337.4 g/mol.
It is presented as a crystalline white to off white powder. It is
soluble in methanol. LIN melting point is 181.5–182.5
C.[3–5]
It is officially assayed by liquid chromatography.[4,5]
as the basic nucleus in its chemical structure acts primarily as
a bacteriostat and is frequently involved against the organ-
isms that manifest various superinfections which are gener-
ally more difficult to treat. They are also used to treat the
highly resistant staphylococci in alternative to the penicillin-
ase-resistant penicillin’s and other b-lactams as well as to
erythromycin, aminoglycosides, tetracyclines, etc. LIN is rap-
idly and completely absorbed orally, partly metabolized non-
enzymatically and excreated in urine. Its t1/2 is 5 hours.[2]
Considering the importance of these drugs to the global
population, these drugs require accurate and most reliable
quality control measures. Analytical methods form one of
the most important quality control tools in pharmaceutical
industry required by the regulatory authorities worldwide
for verifying the suitability of these pharmaceutical ingre-
dients and their formulations. This urges the need for com-
pilation of the reported analytical methods for the
estimation of LIN.
The main objective is to present a classified, summarized
review and to discuss the different proposed methods avail-
able for the estimation of LIN in formulations and in bio-
logical matrix. The overview of the analytical methods
employed for the estimation of LIN is shown in Figure 2.
Figure 3 provides a graphical representation of number of
articles published for quantification of LIN from 1999
to 2018.

CONTACT K. S. Kokilambigai kokilampharm@gmail.com Department of Pharmaceutical Analysis, SRM College of Pharmacy, SRM Institute of Science and
Technology, Kattankulathur, Kancheepuram 603203, Tamil Nadu, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/batc.
ß 2019 Taylor & Francis Group, LLC
2 K. S. KOKILAMBIGAI ET AL.
2. Optical methods
2.1. UV/vis spectrophotometric methods
Spectrophotometric methods can be used in laboratories for
the determination of the drugs where modern and high
priced apparatuses such as those required for GC or HPLC
Figure 1. Chemical structure of linezolid.
Figure 2. Overview of analytical methods for the estimation of linezolid.
Figure 3. Number of analytical methods reported from 1999 to 2018.
are not available. These methods being versatile and eco-
nomical especially for developing countries. They have sev-
eral advantages such as being simple, easy, less cost, and less
time consuming compared to the other methods.[6] Table 1
summarizes the spectrophotometric methods available for
the quantification of LIN as single entity[7–21] or in combin-
ation with other drugs.[22–36]
2.2. Spectrofluorimetric method
Apart from UV visible spectrophotometric methods, LIN
has been estimated by spectrofluorimetric method based on
the enhanced fluorescence of LIN in phosphate buffer pH 5,
excitation and emission being at 260 and 380 nm. Linearity
was between 20 and 400 ng/mL. LOD and LOQ were found
to 4.28 and 12.95 ng/mL, respectively.[37]
3. Chromatographic methods
3.1. High performance liquid chromatography (HPLC)
In the midst of various analytical methods, HPLC represents
the most popular chromatographic method for the quantifi-
cation of the drug(s). Also HPLC is one of the most reliable
methods for the quantification characterized by its accuracy,
ruggedness and sensitivity.[38] The HPLC methods available
for the quantification of LIN as single[19,21,39–44] or in fixed
dose combinations are represented in Table 2.[23,45–51]
 CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY 3

Table 1. Analytical data for the reported spectrophotometric methods.

Drug Matrix Solvent/reagent Detection (nm) Linearity (mg/mL) LOD (mg/mL) LOQ (mg/mL) Ref.
[7]
LIN Tablets Distilled water/ 755 2.5–80 0.5332 1.6158
Folin–Ciocalteu
reagent
[8]
LIN Tablets ACN/ 420 5–25 NA NA
Tetracyano ethylene
[9]
LIN Bulk, tablets Distilled water 251 1–6 0.603 0.830
[10]
LIN Tablets 0.1 N HCl 220–230 12–18, NA NA
2.4–3.6, 1.2–1.8
[11]
LIN Tablets 0.05 N HCl 252 1–6 0.36 1.11
[12]
LIN Tablet A. MeOH/0.1 A. 258.2 4–18 A. 0.18 A. 0.54
N NaOH
B. MeOH/0.1 N HCl B. 253–263 B. 0.08 B. 0.24
[13]
LIN Bulk, tablets A. FeCl3/1, 10 A. 510 A. 0.5–6 A. 0.15 A. 0.46
phenanthroline
B. FeCl3/ B. 522 B. 0.5–9 B. 0.17 B. 0.52
2,2’ bipyridyl
C. FeCl3/potassium C. 758 C. 1.0–9 C. 0.17 C. 0.53
ferric cyanide
[14]
LIN Pure, tablets Ferric citrate/1,10 510 1–10 NA NA
phenanthroline
[15]
LIN Injection Ultra purified water 254 NA NA NA
[16]
LIN Pure, tablets Distilled water 291 3–18 0.09784 0.2951
[17]
LIN (SIAM) Bulk FeCl3/1, 10 510 NA NA NA
phenanthroline
[18]
LIN Bulk, tablets 20% MeOH 251 2–16 0.1459 0.4421
[19]
LIN Tablets 0.1 N HCl 227.2, 260.9, 1–14 NA NA
252, 245.6
[20]
LIN Tablets Chloroform/bromoc- 420 0–70 NA NA
resol green
[21]
LIN Tablets 0.1 M HCl/0.35% 627 1.6–12 0.099 0.33
MBTH/0.4% FeCl3
[22]
CEF, LIN Tablets 0.2 N NaOH 250, 286 2–12 0.2883, 0.4243 0.9513, 1.4001
[23]
CEF, LIN Tablets MeOH 257, 279 2–10, 6–30 0.031, 0.009 0.096, 0.029
[24]
LIN, CEF Tablets MeOH 257, 288 10–50 NA NA
CEF, LIN Tablets – 259, 290 6–14, 7–15 NA NA [25]
[26]
CEF, LIN Tablets 0.1 N NaOH 236.6, 247.6 2–30 0.327, 0.443 0.993, 1.343
[27]
CEF, LIN Tablets 0.05 M potassium 250.6, 287.2 2–22, 2–18 0.38, 0.21 1.14, 1.31
phosphate buffer,
pH 7.2
[28]
CEF, LIN Tablets MeOH 228, 290 2–18, 7–15 0.510, 0.689 1.545, 2.090
[29]
CEF, LIN Tablets MeOH A. 276.6, 301 2–6, 6–18 A. 0.3466, 0.1931 A. 1.0505, 0.5852
B. 257.4, 289.4 B. 0.2877, 0.2435 B. 0.8719, 0.7380
C. 268.2, 233.3 C. 0.368, 0.114 C. 1.116, 0.348
[30]
CEF, LIN Tablets MeOH 259, 289 3–7, 9–21 0.24, 0.19 0.73, 0.58
[31]
CEF, LIN Tablets MeOH 250.7, 278.7 2–10, 5–25 0.2, 0.8 0.6, 2.5
[32]
CEF, LIN Tablets MeOH 257, 289 5–40, 10–30 0.46, 0.75 1.42, 2.27
[33]
CFX, LIN Synthetic mixture MeOH 257.7, 276.8 5–25, 6–30 5.77, 2.81 17.48, 8.52
[34]
CFX, LIN Tablets MeOH 257.4, 276.6 2–6, 2.4–7.2 NA NA
[35]
CFX, LIN Tablets MeOH 257.4, 276.6 2–6, 2.4–7.2 0.065, 0.972 0.198, 1.475
[36]
CFX, LIN Tablets MeOH A. 257, 277 A. 3–11, 3.6–13.2 NA NA
B. 257, 272 B. 3–11, 3.6–13.2
C. 256, 275 C. 12–36
LIN – linezolid; CEF – cefixime trihydrate; CFX – cefuroxime axetil; LOD – limit of detection; LOQ – limit of quantification; ACN – aceto-
nitrile; N – normal; HCl – hydrochloric acid; FeCl3 – ferric chloride; MeOH – methanol; NaOH – sodium hydroxide; MBTH – 3-methyl-2-
benzothiazolinone hydrazone hydrochloride; SIAM – stability indicating assay methods; mg/mL – microgram per milliliter;
NA – not available.

3.2. High performance thin layer
chromatography (HPTLC)
Instrumental planar chromatography is regarded as reliable,
fast, and accurate technique for qualitative as well as quanti-
tative drug analysis; it proves to be an alternative method
for the assay of drugs.[52] Few HPTLC methods are available
for the determination of LIN alone and in combination
Patel et al. have developed a HPTLC method for the ana-
lysis of LIN in its tablet formulation. The stationary phase
consisted of Silica Gel 60 F254 TLC plates with a mobile
phase of MeOH:benzene in the ratio 2:8 v/v. The densito-
metric detection was done at 258 nm and the Rf value was
found to be 0.45 ± 0.03. Linearity was between 200 and
1,400 ng/spot. The limit of detection and limit of quantifica-
tion were 16.7 and 50.7 ng/spot, respectively.[53] Another art-
icle describes a SIAM for the quantification of LIN as bulk
and in formulations. TLC aluminum plates precoated with
Silica Gel 60 F254 was used as the stationary phase and the
solvent system comprised of toluene:ACN (5:5 v/v) with
densitometric analysis at 254 nm. A good linear relationship
was obtained between 300 and 800 ng/spot. The limit of
detection and limit of quantification were 20 and 50 ng/spot
respectively.[54] The simultaneous determination of LIN with
CEF has been reported by Jaiprakash Sangshetti et al. The
4 K. S. KOKILAMBIGAI ET AL.

Table 2. Summary of the reported high performance liquid chromatographic methods.

Flow rate
Drug Column Mobile phase Wavelength (nm) (mL/min) CT (
C) Linearity (mg/mL) Rt (min) Ref.
[39]
LIN C18, Inertsil ODS- MeOH:ammonium 251 1.0 50 25–75 3.827
3V dihydrogen
(150  4.6 mm, phosphate
5 mm) (0.002 M ),
50:50 v/v
[19]
LIN ZORBAX Eclipse- 258 1 Ambient 2–24 2.973
C18 (150  10 mM KH2PO4
4.6 mm, 5 mm) pH adjusted to
3:MeOH:ACN,
60:20:20 v/v/v
[40]
LIN Phenomenex Buffer:MeOH, 251 1.5 300 1–6 15.14
Luna C18 65:35 v/v
(250  4.6 mm,
5 mm)
[41]
LIN Hypersil ODS C Water:MeOH, 254 1 25 1–3,400 5.117
18 50:50 v/v.
(250  4.6 mm,
5 mm)
[42]
LIN Thermo Hypersil Orthophosphoric 251 1 NA NA 6.2
C18 buffer:ACN,
(150  4.6 mm) 80:20 v/v
[21]
LIN Phenomenex ODS MeOH:water, 240 2 25 5–40 3.9
(250  4.6 mm, 65:35 v/v
5 mm)
LIN (SIAM) Waters C18 254 1 25 –8 to 20 4.6 [43]

(250  4.6 mm, 1% acetic

5 mm) acid:MeOH:ACN,
50:25:25 v/v/v
[44]
LIN Kromasil C8 Water:ACN, 80:20 254 1 NA 0.39–25 10.4
(150  4.6 mm, v/v
5 mm)
[45]
CEF, LIN Inertsil ODS C 18, 272 1 300 8–45, 24–144 3.161, 4.774
(150  4.6 mm, 0.1 M NaH2PO4
5 mm) pH 4.7:ACN, 60:40
v/v
[46]
CEF, LIN Reverse phase C MeOH:KH2PO4 277 1 NA 5–15, 15–45 3.76, 6.55
18 Hypersil buffer, pH
BDS adjusted to 3.5
(250  4.6 mm, with TEA,
5 mm) 40:60 v/v
[23]
CEF, LIN Phenomenex Water:MeOH:ACN, 279 1 NA 0.01–15, 0.03–45 1.5, 3.9
Luna C 18 40:30:30 v/v/v
(250  4.6 mm,
5 mm)
[47]
CEF, LIN (SIAM) Phenomenex Phosphate buffer 276 1 NA 2–12, 6–36 3.127, 11.986
Luna C 18 pH 7:MeOH,
(250  4.6 mm) 60:40 v/v
5 mm
[48]
CEF, LIN ACE 5 C18 Buffer:MeOH pH 250 1.2 NA 23.33–40, 70–120 3.30, 8.07
(150  4.6 mm, 2.5, 70:30 v/v
5 mm)
[49]
CFX, LIN Systronics C18 Phosphate buffer, 276 1 NA 2–12, 6–36 3.127, 11.986
(250  4.6 mm, pH 7:MeOH,
5 mm) 60:40 v/v
[50]
CFX, LIN Thermo ACN:water, 65:35 267 0.8 NA 6–30, 5–25 4.273, 3.573
Synchronies v/v
C18
(250  4.6 mm,
5 mm)
[51]
LIN, LEV Genesis C18 Ammonium acet- 236 0.8 25 2–24, 0.2–2.4 4.61, 6.45
(250  4.6 mm, ate pH 4:ACN,
4 mm) 65:35 v/v
LIN – linezolid; CEF – cefixime trihydrate; CFX – cefuroxime axetil; LEV – levamisole hydrochloride; SIAM – stability indicating assay method;
MeOH – methanol; nm-nanometer; mL/min – milliliter per minute;
C – degree centigrade; CT – column temperature; mg/mL – microgram
per milliliter; mM – millimolar; Rt – retention time; KH2PO4 – potassium dihydrogen phosphate; NaH2PO4 – sodium dihydrogen phosphate;
ACN – acetonitrile; NA – not available.

separation was achieved on pre-coated Silica Gel 60 F254 4. Bioanalytical methods

employing MeOH:ethyl acetate:ammonia in the ratio 6:4:0.2
v/v/v. Linearity was between 150 and 1,050 ng/spot for both Bioanalytical methods are utilized for the quantification of
the drugs. The method was validated as per ICH the drugs and their metabolites in biological fluids thereby
guidelines.[55] play a major role in the determination and interpretation of
Table 3. Summary of bioanalytical methods for the quantification of LIN alone and in combination with other drugs.
Drug Method Matrix Sample preparation Column/mobile phase Rt (min) Detection Linearity Ref.
[57]
LIN UPLC-MS/MS Rabbit plasma With diethyl ether BEH C18/2 mM ammonium acetate 1.16 m/z 338, 296.08 50–5,000 ng/mL
buffer:ACN, 70:30 v/v
[58]
LIN HPLC Human plasma Precipitation with protein Agilent ODS C18/ACN:water:MeOH, NA 251 nm 0.75–50 mg/mL
20:70:10 v/v/v
[59]
LIN HPLC Human plasma, SALIVA With ethyl acetate Capcell Pak C18/ACN:THF:0.5% NA 254 nm 0.5–50 mg/mL
ammonium acetate buffer pH 4.4,
17:5:78 v/v/v
[60]
LIN LC-MS/MS Serum protein precipitation and on- Kinetex XB-C18/water:ACN:formic 2.5 NA 0.13–32 mg/L
line solid phase extraction acid, 89.9:10:0.1 v/v/v
with two dimensional
liquid chromatography and
column switching
[61]
LIN LC-MS Human plasma Protein precipitation, SPE, ACE C8/MeOH:water, 50:50 v/v NA 251 nm 1–30 mg/mL
microextraction in 1–50 mg/mL
packed syringe
[62]
LIN HPLC Human serum MeOH RP C18/50 mM phosphate buffer:ACN, NA NA 0.50 to 30.0 g/mL
76:24 v/v
[63]
LIN LC-MS/MS Dried blood spot With 300 mL mixture Agilent Zorbax Eclipse Plus C18/0.1% NA 254 nm 1–100 mg/L
30:70:0.05 (v/v/v) water, formic acid:10% ACN, gradi-
ACN, formic acid ent elution
[64]
LIN HPLC Human plasma, bron- SPE C18/dihydrogen phosphate buffer 3.78 PDA 25–25,600 ng/mL
choalveolar lavage 50 mM:ACN, 60:40 v/v
[65]
LIN HPLC Human plasma Precipitation with protein X Bridge C18/0.05% phosphoric 4.0 254 nm 0.2–48 mg/L
acid:ACN, 75:25 v/v
[66]
LIN HPLC Pig pulmonary tissue 1 ¼ TBE (1 M Tris, 0.9 M Novapak C18/20% water, 80% potas- 11-12 254 nm 1.6–100 mg/mL
boric acid, 0.01 M EDTA). sium monohydrogen phosphate
buffer:ACN, 80:20 v/v
[67]
LIN HPLC Human Plasma With 10% MeOH –90% Symmetry C18/0.5% ammonium acet- NA 251 nm 0.05–40 mg/L
dichloromethane ate, pH 4.4:ACN, 84:16 v/v
[68]
LIN HPLC Human serum NA Hypersil ODS/ACN:water, 23:77 v/v NA 254 0.31–20.00 mg/L
[69]
LIN HPLC Dog, rat, mouse and rab- SPE Zorbax RXC8/water:ACN, 20:80 v/v 10-11 251 nm 0.01–20 mg/mL
bit Plasma
[70]
LIN HPLC Human breast milk protein precipitation C18/ACN:10 mM acetic acid, 25:75 v/v NA 250 nm 0.5–20.0 mg /mL
[71]
LIN HPLC Different biomatrices Proteins were precipitated Luna C8/water:ACN, 80:20 v/v NA 251 nm 0.5–40 mg/mL
with ACN
[72]
LIN LC-MS Human Serum Precipitation of proteins HyPurity Aquastar C18/aqueous 2.7 m/z 338.1 to 0.05–40.0 mg/L
buffer:water:ACN, Gradient eluiton m/z 296.1
[73]
LIN HPLC Human plasma Protein precipitation PhenoSphere-NEXT C18/ACN:2.67 mM 5.5 253 nm 0.20–40.0 mg/L
acetic acid, 25:75 v/v
[74]
LIN HPLC Human plasma, bron- SPE Zorbzx Eclipse XDB C8/water with 9.10 254 0.02–30 mg/mL,
choalveolar lavage 0.4% TEA:ACN, Gradient elution 0.04–30 mg/mL
[75]
LIN HPLC Brain heart infusion broth Protein precipitation PhenoSphere-NEXT C18/ACN:2.67 mM NA 253 0.05–16 mg/L
acetic acid, 25:75 v/v
[76]
LIN HPLC Microdialysate, With ACN Spherimage-80 ODS/25 mM sodium 5 251 nm 8–200 mg/mL,
human plasma acetate buffer pH 5:ACN, 80:20 v/v 2–200 mg/mL
[77]
LIN HPLC Serum Continuous ambulatory peri- Hypersil 5 ODS/1% ortho phosphoric 6 254 0–50 mg/L
toneal dialysis fluid by acid:30% MeOH:2 g/L heptane sul-
mixing with ACN fonic acid pH 5
[78]
LIN HPLC Serum and urine Inline extraction Nucleosil C18/50 mM NaH2PO4:ACN, NA 260 nm 0.64–32 mg/mL
gradient elutin
[79]
LIN LC-MS-MS Human plasma SPE Shim Pack CLC-CN C18/ACN, 20 mM 3.44 m/z 338, 296.2 0.1–5 mg/mL
CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY

ammonium acetate, 80:20 v/v

[80]
LIN HPLC Human serum With ACN 6.5 254 0–30 mg/mL
(continued)
5
 6 K. S. KOKILAMBIGAI ET AL.
Ref.

LIN – linezolid; Rt – retention time; UPLC-MS/MS – ultra performance liquid chromatography–tandem mass spectrometry; HPLC – high performance liquid chromatography; LC-MS/MS – liquid chromatography–tandem
the bioequivalence, pharmacokinetic and toxicokinetic stud-

[81]

[82]

[83]

[84]

[85]

[86]

[87]

[88]
ies.[56] Table 3 summaries the bioanalytical methods
reported for the quantification of LIN alone[57–81] and in

10–10,000 ng/mL
500–5000 ng/mL

0.1–30, 0.05–5,

0.3–20, 2.4–20,
20–150 ng/mL,
combination with other drugs.[82–88]

0.1–10 mg/mL

0.3–10 mg/mL
0.78125–100
2–40, 6–120
Linearity

5–5,000,
20 mg/L

mg/mL

mg/mL

NA
5. Miscellaneous methods
A microbiological assay for LIN has been reported by
Lourenco et al. The potency of LIN in injection was

mass spectrometry; TED – tedizolid; RAM – rifampicin; DAP – daptomycin; SPE – solid phase extraction; ACN – acetonitrile; MeOH – methanol; NaH2PO4 – sodium dihydrogen phosphate.
m/z 371.4, 343.2
m/z 338.3, 56.1

reported employing design of experiments. The article also

Detection

336 nm

254 nm

214 nm

260 nm

292 nm

280 nm
reports the comparison of the methods measurement uncer-
250

tainty with other methods like spectrophotometry, RP-

UPLC.[89] Another article reported by the same author
utilizes quality by design approach for the determination of
LIN by micro plate bioassay. Fractional factorial design was

12.55, 17.25
5.35, 11.45, adopted to study the influence of culture media composition
4.1, 17.4
Rt (min)

and CCD was adopted to optimize the experimental condi-

6.6

NA

NA

NA

NA

NA

tions. Linearity was found to be between 1 and 10 mg/mL.[90]

Mohamed et al. have reported the electroanalytical sens-
ing of LIN. Linearity was found to be between 5  108 and
1.45  104 mol/L.[91] Merli et al. have reported a differential
Atlantis C18/50 mM dihydrogen phos-
Nucleosil-100 5C18/ACN:sodium acet-

phate buffer:ACN, gradient elution

acid:30% MeOH:2 g/L heptane sul-

phosphate buffer pH 4:ACN, 70:30

Hypersil 5 ODS/1% ortho phosphoric

Chromolith SpeedROD RP18/0.15 M

Hypersil BDS C8/40 mM ammonium

Acquity UPLC BEH C18/0.1% formic
ate buffer:water, 18:10:72 v/v/v

pulse voltammetric method based on the oxidation of LIN

TEA:10% propanol in 0.02 M
sodium dodecyl sulfate:0.3%

at glassy carbon electrode.[92]

orthophosphoric acid, pH 6
Column/mobile phase

acid in water:ACN, gradi-

NaH2PO4:ACN, 75:25 v/v

Powder X-ray diffraction technique was utilized by

Hypersil BDS C18/20 mM

Xiurong HU for the determination of minor quantities of

fonic acid pH 5

LIN polymorphs. LIN was found to have five polymorphic

forms and the most stable and commercial polymorphs were
ent elution

forms II and IV. This article quantifies LIN in its poly-

morphic form II.[93] Cristiani et al. have reported an agar
v/v
NA

NA

diffusion assay method to estimate the potency of LIN in

tablets in the presence of its photodegradation products.
Cylinder plate method was applied to determine and evalu-
ate the stability of LIN in tablets.[94] A capillary electrophor-
Sample preparation

etic method using sweeping preconcentration followed by

Protein precipitation

Protein precipitation

Protein precipitation

UV absorption detection was reported for the separation of

With ethyl acetate

LIN from its achiral impurities. Sodium dodecyl sulfate was

used as the sweeping agent and the background electrolyte con-
sisted of 125 mM Tris buffer, pH 2, with 20% v/v MeOH.[95]
NA

NA

NA

NA

6. Discussion
LIN as the first member of the oxazolidinone group of drugs
Rat plasma, rat tissue

has given a notable contribution since its approval from

Matrix

human urine

human urine
Human plasma,

2000 in its pharmaceutical dosage forms namely tablet,

Human plasma

Human plasma

Human plasma

Human plasma
Human serum,

injection, infusion, and syrup. UV-visible spectrophotomet-

Rat plasma

ric technique is most commonly utilized for the determin-

ation of LIN as a single drug and in combination with other
drugs in bulk and pharmaceutical formulations. It can be
noticed that MeOH is commonly used as the solvent for the
Micellar HPLC
Spectrofluori-

estimation of LIN in combination by spectrophotometric

Method

UPLC-MS

methods. Few methods have been reported for its estimation

metry
HPLC

HPLC

HPLC

HPLC

HPLC

in combination with other drugs by HPLC in pharmaceuti-

Table 3. Continued.

cals and a notable number for biological matrix. Only

countable number of LC-MS/MS methods are available for
5 drugs

4 drugs

3 drugs

the estimation of the drug in biological fluids. Most bioana-

LIN, RAM

LIN, DAP
TED, LIN

lytical methods reported for the quantification of LIN uti-

LIN þ

LIN þ

LIN þ
Drug

LIN

LIN

lizes either SPE or extraction with an organic solvent as the

 CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY 7

sample preparation technique. It was also noted that hardly Acknowledgments

SIAM are available for the estimation of LIN. The authors are thankful to Vice Chancellor, SRM University and
management of SRM College of Pharmacy, SRM University,
Kattankulathur for providing various reprographic sources for carrying
out this work.
7. Conclusion
From the present review, the analytical methods available
Conflict of interest
for the estimation of LIN includes wide range of analytical
techniques like spectrophotometry, spectrofluorimetry, chro- The authors declare that there are no conflicts of interest.
matography, microbiological assay methods. Also this review
has witnessed significant number of methods over past References
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