38 Ferumoxsil / Official Monographs
I = concentration of iron in the Injection (mg/g),
obtained by using specific gravity to convert
the concentration of iron (mg/mL), as
determined in the Assay for Iron, to mg/g
Acceptance criteria: NLT 22,500 10-6 in cgs units/g of
iron
SETTLING: NLT 80% is found
Sample solution: Prepare a mixture of Oral Suspension and
water (1:5).
Blank: Water
Spectrometric conditions
Analytical wavelength: 500 nm
Analysis: Mix the Sample solution by gentle inversion, and
determine the absorbance. Cover the cell, and allow to
stand undisturbed for 4 h at room temperature. Without
mixing, determine the absorbance again.
Calculate the percentage of iron remaining in solution after
settling taken:
Result = (A4/A0) 100
A4 = absorbance of the solution after standing for 4 h
A0 = initial absorbance of the solution
Acceptance criteria: NLT 80%
DELIVERABLE VOLUME 698: For Oral Suspension packaged in
multiple-unit containers: Meets the requirements
ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight containers, and
store at controlled room temperature.
LABELING: Label it to indicate that it is to be well-shaken for
1 min before use, and that it is not to be used if there are
indications that the package has been exposed to freezing
temperatures.
Fexofenadine Hydrochloride
(Comment on this Monograph)id=m33074=Fexofenadine
Hydrochloride=F-Monos.pdf)
C32H39NO4 HCl 538.12
Benzeneacetic acid, 4-[1-hydroxy-4-[4-
(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-, -dimethyl-,
hydrochloride, ()-;
()-p-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)piperidino]butyl]-
-methylhydratropic acid, hydrochloride [138452-21-8].
DEFINITION
Fexofenadine Hydrochloride contains NLT 98.0% and NMT
102.0% of C32H39NO4 HCl, calculated on the anhydrous basis.
IDENTIFICATION
A. INFRARED ABSORPTION 197K
B. The retention time of the major peak in the Sample
solution corresponds to that in the Standard solution, as
obtained in the Assay.
C. PROCEDURE
Analysis: Examine the precipitate formed in the Content of
Chloride test.
Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
USP 32
Acceptance criteria: A white precipitate is observed.
ASSAY
PROCEDURE
Solution A: 6.64 g/L of monobasic sodium phosphate and
0.84 g/L of sodium perchlorate in water, and adjust with
phosphoric acid to a pH of 2.0
Diluent: Acetonitrile and Solution A (1:1)
Mobile phase: Acetonitrile and Solution A (7:13)
[NOTEAdd 3 mL of triethylamine/L in Mobile phase]
Standard solution: 0.06 mg/mL of USP Fexofenadine
Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine
Related Compound A RS in Mobile phase
Sample stock solution: 1.0 mg/mL of fexofenadine
hydrochloride in Diluent
Sample solution: 0.06 mg/mL from the Sample stock
solution in Mobile phase
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220-nm
Column: 4.6-mm 25-cm; packing L11
Flow rate: 1.5 mL/min
Injection size: 20 L
System suitability
Sample: Standard solution
Suitability requirements
Resolution: NLT 10 between fexofenadine and
fexofenadine related compound A
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0% and 3.0% from
fexofenadine and fexofenadine related compound A
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage, of C32H39NO4 HCl in the portion
of Fexofenadine Hydrochloride:
Result = (rU/rS) (CS/CU) 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
(mg/mL)
CU = nominal concentration of fexofenadine
hydrochloride in the Sample solution (mg/mL)
Acceptance criteria: 98.0%102.0%
OTHER COMPONENTS
CONTENT OF CHLORIDE
Sample solution: 6 mg/mL of Fexofenadine Hydrochloride,
in methanol
Analysis: Titrate with 0.1 N silver nitrate VS (see Titrimetry
541). Each mL of 0.1 N silver nitrate VS is equivalent to
3.545 mg of chloride.
Acceptance criteria: 6.45%6.75%, calculated on an
anhydrous basis
IMPURITIES
Inorganic Impurities
RESIDUE ON IGNITION 281: NMT 0.1%
HEAVY METALS, Method II 231: 20 ppm
Organic Impurities
PROCEDURE 1: LIMIT OF FEXOFENADINE RELATED COMPOUND B
Solution A: Glacial acetic acid and water (2.3:2000).
Adjust with 6 N ammonium hydroxide to a pH of 4.0 0.1.
USP 32 Official Monographs / Fexofenadine 39

Mobile phase: Acetonitrile and Solution A (1:4) CU = concentration of Fexofenadine in the Sample
System suitability solution: Add 1.2 mg of USP solution (mg/mL)
Fexofenadine Related Compound B RS, to a 5-mL Calculate the percentage of decarboxylated degradant
volumetric flask. Dilute with Mobile phase to volume. [(+)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-
Transfer 2.0 mL of the solution into a 100-mL volumetric piperidinyl]-butyl]-isopropylbenzene], with a relative
flask; add 25 mg of USP Fexofenadine Hydrochloride RS, retention time of 3.2, in the portion of Fexofenadine
and dilute with Mobile phase to volume. Hydrochloride taken:
Standard solution: 2.5 g/mL of USP Fexofenadine
Hydrochloride RS in Mobile phase Result = (rU/rS) (CS/CU) 1/F 100
Sample solution: 0.25 mg/mL of Fexofenadine
Hydrochloride in Mobile phase rU = peak response of the decarboxylated degradant
Chromatographic system from the Sample solution
(See Chromatography 621, System Suitability.) rS = peak response of fexofenadine from the Standard
Mode: LC solution
Detector: UV 220 nm CS = concentration of USP Fexofenadine
Column: 4.6-mm 25-cm; packing L45 Hydrochloride RS in the Standard solution
Flow rate: 0.5 mL/min (mg/mL)
Injection size: 20 L CU = concentration of Fexofenadine in the Sample
System suitability solution (mg/mL)
Sample: System suitability solution F = response factor for the decarboxylated
[NOTEThe relative retention times for fexofenadine degradant relative to fexofenadine, 1.1
related compound B and fexofenadine are about 0.7 Calculate the percentage of other impurities in the portion
and 1.0, respectively.] of Fexofenadine Hydrochloride taken:
Suitability requirements
Resolution: NLT 3.0 between fexofenadine and Result = (rU/rS) (CS/CU) 100
fexofenadine related compound B
Analysis rU = peak response for any other impurity from the
Samples: Standard solution and Sample solution Sample solution
Calculate the percentage of fexofenadine related rS = peak response of fexofenadine from the
compound B in the portion of Fexofenadine Reference solution
Hydrochloride: CS = concentration of fexofenadine in the Reference
solution (mg/mL)
Result = (rU/rS) (CS/CU) 1/F 100 CU = concentration of Fexofenadine in the Sample
solution (mg/mL)
rU = peak response for fexofenadine related Acceptance criteria
compound B from the Sample solution Individual impurities: See Impurity Table 1.
rS = peak response for fexofenadine from the Total impurities: NMT 0.5%
Standard solution
CS = concentration of USP Fexofenadine Impurity Table 1
Hydrochloride RS in the Standard solution
Acceptance
(mg/mL)
Criteria, NMT
CU = concentration of Fexofenadine in the Sample
Name (%)
solution (mg/mL)
F = response factor for fexofenadine related Fexofenadine related compound A 0.2
compound B relative to fexofenadine, 0.8 Decarboxylated degradant 0.15
Acceptance criteria: NMT 0.2%
Any other unknown individual impurity 0.1
PROCEDURE 2: RELATED COMPOUNDS
Solution A, Diluent, Mobile phase and Chromatographic
system: Prepare as directed in the Assay. SPECIFIC TESTS
Standard solution: Use Standard solution under Assay. WATER DETERMINATION, Method Ic 921: NMT 0.5% for the
Sample solution: Use Sample stock solution under Assay. anhydrous form; 6.0%10.0% for the hydrate form
Reference solution: Use Sample solution under Assay. [NOTEHydrate refers to a mixture of dihydrate and
Samples: Standard solution, Sample solution, Reference trihydrate forms of fexofenadine hydrochloride.]
solution, and Mobile phase (used as the blank)
Record the chromatograms, and measure the peak areas, ADDITIONAL REQUIREMENTS
excluding the peaks corresponding to those from the PACKAGING AND STORAGE: Preserve in well-closed, light-
Mobile phase. resistant containers, and store at controlled room
Calculate the percentage of fexofenadine related temperature.
compound A in the portion of Fexofenadine LABELING: Where it is the hydrate form, the label so
Hydrochloride: indicates.
USP REFERENCE STANDARDS 11
Result = (rU/rS) (CS/CU) 100 USP Fexofenadine Hydrochloride RS
USP Fexofenadine Related Compound A RS
rU = peak response for fexofenadine related USP Fexofenadine Related Compound B RS
compound A from the Sample solution
rS = peak response for fexofenadine related
compound A from the Standard solution
CS = concentration of USP Fexofenadine Related
Compound A RS in the Standard solution
(mg/mL)

Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
40 Fexofenadine / Official Monographs
Fexofenadine Hydrochloride Capsules
(Comment on this Monograph)id=m33075=Fexofenadine
Hydrochloride Capsules=F-Monos.pdf)
DEFINITION
Fexofenadine Hydrochloride Capsules contain NLT 93.0% and
NMT 105.0% of the labeled amount of fexofenadine
hydrochloride (C32H39NO4 HCl).
IDENTIFICATION
A. The retention time of the major peak in the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
B. INFRARED ABSORPTION 197K
Sample solution: Empty an equivalent to 60 mg of
fexofenadine hydrochloride, from the contents of several
Capsules, into a suitable capped tube. Add 10 mL of a
mixture of acetonitrile and methanol (10:1), and shake until
the sample is dispersed. Allow to settle. Decant, filter, and
collect the supernatant in a suitable beaker. Evaporate the
solvent to near dryness by using a stream of nitrogen and
with gentle heating from an appropriate source (steam, low-
temperature hot plate). While still warm, add 5 mL of water
and 5 drops of diluted hydrochloric acid, and stir to induce
precipitation. Chill in an ice bath for about 30 min. Pass
through a 10- to 15-m filtering crucible with fritted disk.
Dry the precipitate in an air oven for 1 h at 105.
ASSAY
PROCEDURE
Solution A: 6.64 g/L of monobasic sodium phosphate and
0.84 g/L of sodium perchlorate in water, and adjust with
phosphoric acid to a pH of 2.0
Diluent: Acetonitrile and Solution A (1:1)
Mobile phase: Acetonitrile and Solution A (7:13)
[NOTEAdd 3 mL of triethylamine/L in Mobile phase.]
Standard solution: 0.06 mg/mL of USP Fexofenadine
Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine
Related Compound A RS in Mobile phase
Sample stock solution: Remove, as completely as possible,
the contents of NLT 20 Capsules, mix the combined
contents, and finely powder by using a mortar and pestle.
Shake by mechanical means for 60 min. Transfer a portion
of the powder equivalent to 50 mg of fexofenadine
hydrochloride in 40 mL of Diluent. Sonicate for about 2 min.
Allow to cool to room temperature, and dilute with Diluent
solution to 50 mL.
Sample solution: Transfer 3.0 mL of the Sample stock
solution to a 50-mL volumetric flask, and dilute with Mobile
phase to volume.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220 nm
Column: 4.6-mm 25-cm; packing L11
Flow rate: 1.5 mL/min
Injection size: 20 L
System suitability
Sample: Standard solution
Suitability requirements
Resolution: NLT 10 between fexofenadine and
fexofenadine related compound A
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0% and 3.0% from
fexofenadine and fexofenadine related compound A
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of C32H39NO4 HCl in the portion
of Capsules taken:
Result = (rU/rS) (CS/CU) 100
Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
USP 32
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
(mg/mL)
CU = nominal concentration of fexofenadine
hydrochloride in the Sample solution (mg/mL)
Acceptance criteria: 93.0%105.0%
PERFORMANCE TESTS
DISSOLUTION 711
TEST 1
Medium: Water; 900 mL
Apparatus 2: 50 rpm
Time: 15 and 45 min
Determine the amount of C32H39NO4 HCl dissolved by
employing the following method.
Solution A: 1.0 g of monobasic sodium phosphate, 0.5 g
of sodium perchlorate, and 0.3 mL of phosphoric acid in
300 mL of water
Mobile phase: Acetonitrile and Solution A (7:3)
System suitability stock solution: 0.44 mg/mL of USP
Fexofenadine Related Compound A RS in water [NOTEA
small amount of glacial acetic acid, not to exceed 5% of
the total volume, is used, if necessary, to dissolve USP
Fexofenadine Related Compound A RS.]
System suitability solution: USP Fexofenadine
Hydrochloride RS in System suitability stock solution
containing 0.01 mg/mL of USP Fexofenadine Related
Compound A RS and 0.06 mg/mL of USP Fexofenadine
Hydrochloride RS
Standard solution: 0.07 mg/mL of USP Fexofenadine
Hydrochloride RS in water [NOTEA small amount of
methanol, not to exceed 0.5% of the total volume, is used,
if necessary, to dissolve USP Fexofenadine Hydrochloride
RS.]
Sample solution: Sample per Dissolution 711. Dilute with
Medium to a concentration that is similar to the Standard
solution.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220 nm
Column: 4.6-mm 10-cm; packing L1
Flow rate: 1 mL/min
Injection size: 50 L
System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution: NLT 2.0 between fexofenadine and
fexofenadine related compound A, System suitability
solution
Relative standard deviation: NMT 2.0%, Standard
solution
Analysis
Samples: Standard solution and Sample solution
Calculate the quantity of C32H39NO4 HCl dissolved:
Tolerances: NLT 50% (Q) of the labeled amount of
C32H39NO4 HCl is dissolved in 15 min; NLT 75% (Q) of
the labeled amount of C32H39NO4 HCl is dissolved in 45
min.
TEST 2
If the product complies with this test, the labeling indicates
that the product meets USP Dissolution Test 2.
Medium, Apparatus, Solution A, Mobile phase, System
suitability stock solution, System suitability solution,
Chromatographic system, and Analysis: Proceed as
directed for Test 1.
USP 32
Time: 45 min
Tolerances: NLT 75% (Q) of the labeled amount of C32 H39
NO4 HCl is dissolved.
UNIFORMITY OF DOSAGE UNITS 905: Meet the requirements
IMPURITIES
Organic Impurities
PROCEDURE
Solution A: 6.64 mg/mL of monobasic sodium phosphate
and 0.84 mg/mL of sodium perchlorate in water, and
adjust with phosphoric acid to a pH of 2.0
Diluent: Acetonitrile and Solution A (1:1)
Mobile phase: Acetonitrile and Solution A (7:13)
[NOTEAdd 3 mL of triethylamine/L in Mobile phase.]
Standard solution: 0.06 mg/mL of USP Fexofenadine
Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine
Related Compound A RS in Mobile phase
Sample solution: 1.0 mg/mL of fexofenadine
hydrochloride in Diluent
Reference solution: 0.06 mg/mL from Sample solution in
Mobile phase
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220 nm
Column: 4.6-mm 25-cm; packing L11
Flow rate: 1.5 mL/min
Injection size: 20 L
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of fexofenadine related
compound A in the portion of Capsules taken:
Result = (rU/rS) (CS/CU) 100
rU = peak response for fexofenadine related
compound A from the Sample solution
rS = peak response for fexofenadine related
compound A from the Standard solution
CS = concentration of USP Fexofenadine Related
Compound A RS in the Standard solution
(mg/mL)
CU = nominal concentration of fexofenadine in the
Sample solution (mg/mL)
Calculate the percentage of decarboxylated degradant
[(+)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-
piperidinyl]-butyl]-isopropylbenzene], with a relative
retention time of 3.2, in the portion of Fexofenadine
Hydrochloride taken:
Result = (rU/rS) (CS/CU) 1/F 100
rU = peak response of the decarboxylated degradant
from the Sample solution
rS = peak response of fexofenadine from the
Standard solution
CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
(mg/mL)
CU = nominal concentration of fexofenadine in the
Sample solution (mg/mL)
F = response factor for the decarboxylated
degradant relative to fexofenadine, 1.1
Calculate the percentage of other impurities in the portion
of Fexofenadine Hydrochloride taken:
Result = (rU/rS) (CS/CU) 100
rU = peak response for any other impurity from the
Sample solution
rS = peak response of fexofenadine from the
Reference solution
Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
Official Monographs / Fexofenadine 41
CS = concentration of fexofenadine in the Reference
solution (mg/mL)
CU = nominal concentration of fexofenadine in the
Sample solution (mg/mL)
Acceptance criteria
Individual impurities: See Impurity Table 1.
Total impurities: NMT 0.5%
Impurity Table 1
Acceptance
Criteria, NMT
Name (%)
Fexofenadine related compound A 0.4
Decarboxylated degradant 0.2
Any other unknown individual impurity 0.2
ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers. Store at controlled room temperature.
LABELING: When more than one Dissolution test is given, the
labeling states the test used only if Test 1 is not used.
USP REFERENCE STANDARDS 11
USP Fexofenadine Hydrochloride RS
USP Fexofenadine Related Compound A RS
Fexofenadine Hydrochloride Tablets
(Comment on this Monograph)id=m852=Fexofenadine
Hydrochloride Tablets=F-Monos.pdf)
DEFINITION
Fexofenadine Hydrochloride Tablets contain NLT 95.0% and
NMT 105.0% of the labeled amount of fexofenadine
hydrochloride (C32H39NO4 HCl).
IDENTIFICATION
A. INFRARED ABSORPTION 197K
Standard solution: Transfer an equivalent to 60 mg of USP
Fexofenadine Hydrochloride RS, from a sufficient number of
weighed and finely powdreed Tablets, to a capped Sample
tube in 10 mL of a mixture of acetonitrile and methanol
(10:1).
Sample solution: Transfer an equivalent to 60 mg of
fexofenadine hydrochloride, from a sufficient number of
weighed and finely powdered Tablets, to a capped tube, in
10 mL of a mixture of acetonitrile and methanol (10:1).
Analysis: Shake or mix the Standard solution and Sample
solution on a vortex mixer for 12 min to disperse the
sample. Allow the solution to stand for 10 min or centrifuge
for 23 min. Pass the liquid into a 50-mL beaker using a
0.45-m polytetrafluorethlyene syringe filter. Evaporate the
solvent until about 0.5 mL remains using a stream of
nitrogen with gentle heating (do not exceed 75). Add 5 mL
of water and 5 drops of dilute hydrochloric acid, and stir to
induce precipitation. Chill in an ice bath for 30 min. Filter
the solution through a 10- to 15-m sintered-glass crucible.
Dry the precipitate in an air oven for 1 h at 105.
Acceptance criteria: The IR absorption spectrum of a
potassium bromide dispersion of the residue exhibits
maxima only at the same wavelengths as that of a
potassium bromide dispersion of a similar solution using USP
Fexofenadine Hydrochloride RS.
B. The retention time of the major peak in the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
42 Fexofenadine / Official Monographs
ASSAY
PROCEDURE
Solution A: Glacial acetic acid and water (17:1000). Dilute
100 mL of this solution with water to 1 L.
Solution B: Dilute 15 mL of a solution containing
acetonitrile and triethylamine (1:1) with Solution A to 1 L.
Adjust with phosphoric acid to a pH of 5.25.
Diluent: Acetonitrile and Solution A (3:1)
Mobile phase: Acetonitrile and Solution B (9:16)
Standard stock solution: 0.25 mg/mL of USP Fexofenadine
Hydrochloride RS in Diluent
Standard solution: 0.015 mg/mL from Standard stock
solution in Mobile phase
Sample stock solution: Transfer a sufficient number of
whole Tablets (NLT 10) to a suitable volumetric flask, add
Solution A (equivalent to 20% of the total flask volume), and
shake by mechanical means at a high speed for 30 min or
until the Tablets are fully disintegrated and finely dispersed.
Add acetonitrile (equivalent to 80% of the total flask
volume), and shake by mechanical means for 60 min. Dilute
with Diluent to volume. Pass a portion of this solution
through a polytetrafluorethylene filter having a 0.45-m or
finer porosity, and use the filtrate. Dilute, if necessary, with
Diluent to obtain a solution containing an equivalent to 1.2
mg/mL of fexofenadine hydrochloride.
Sample solution: 0.018 mg/mL from Sample stock solution
in Mobile phase
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220 nm
Column: 4.6-mm 25-cm; 5-m packing L11
Temperature: 35
Flow rate: 1.5 mL/min
Injection size: 20 L
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of C32H39NO4 HCl in the portion
of Tablets taken:
Result = (rU/rS) (CS/CU) 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
(mg/mL)
CU = nominal concentration of fexofenadine
hydrochloride in the Sample solution (mg/mL)
Acceptance criteria: 95.0%105.0%
PERFORMANCE TESTS
DISSOLUTION 711
TEST 1
Medium: 0.001 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm
Time: 10 and 30 min
Determine the percentages of the labeled amount of
C32H39NO4 HCl dissolved by using the following method.
Solution A: 1.0 g of monobasic sodium phosphate, 0.5 g
of sodium perchlorate, and 0.3 mL of concentrated
phosphoric acid in 300 mL of water
Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
USP 32
Mobile phase: Acetonitrile and Solution A (7:3)
Standard solution: USP Fexofenadine Hydrochloride RS in
Medium to obtain a solution having a known concentration
similar to that expected for the solution under test
[NOTEA small amount of methanol, not exceeding 0.5%
of the total volume, can be used to dissolve fexofenadine
hydrochloride.]
System suitability solution: 0.44 mg/mL of USP
Fexofenadine Related Compound A RS in water. Transfer
1.0 mL of this solution into a vial, and add 40 mL of the
Standard solution.
[NOTEA small amount of acetic acid, not exceeding 5% of
the total volume, can be used to dissolve fexofenadine
hydrochloride related compound A.]
Sample solution: Sample per Dissolution 711. Dilute with
Medium to concentration that is similar to the Standard
solution. Use portions of the solution under test passed
through a 0.45-m glass fiber filter.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220 nm
Column: 4.6-mm 10-cm; packing L1
Flow rate: 1 mL/min
Injection size: 23 g column load of fexofenadine
hydrochloride
System suitability
Samples: Standard solution and System suitability solution
Suitability requirements
Resolution: NLT 2.0 between fexofenadine and
fexofenadine related compound A, System suitability
solution
Relative standard deviation: NMT 2.0%, Standard
solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of C32H39NO4 HCl dissolved in
the Medium:
Result = (rU/rS) (CS/CU) 100
rU = peak area from the Sample solution
rS = peak area from the Standard solution
CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
(mg/mL)
CU = nominal concentration of fexofenadine
hydrochloride in the Sample solution (mg/mL)
Tolerances: NLT 60% (Q) of the labeled amount of C32H39
NO4 HCl is dissolved in 10 min; NLT 80% (Q) of the
labeled amount of C32 H39 NO4 HCl is dissolved in 30 min.
TEST 2
Medium: 0.001 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm, use paddles and shafts coated with
Teflon.
Time: 30 min
Determine the percentages of the labeled amount of
C32H39NO4 HCl dissolved by using the following method.
Solution A: 7 mg/mL of ammonium acetate in water.
Adjust with glacial acetic acid to a pH of 4.0 0.05.
Mobile phase: Acetonitrile and Solution A (2:3)
Standard solution 1: Transfer 20 mg of USP Fexofenadine
Hydrochloride RS to a 100-mL volumetric flask. Add 3.0 mL
of methanol, and mix. Dilute with Medium to volume.
USP 32
Standard solution 2: Transfer 15.0 mL of Standard solution
1 to a 50-mL volumetric flask. Dilute with Medium to
volume.
Standard solution 3: Transfer 7.5 mL of Standard solution
1 to a 50-mL volumetric flask. Dilute with Medium to
volume.
Sample solution: Sample per Dissolution 711. Use
portions of the solution under test passed through a
suitable 0.45-m filter.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 259 nm
Column: 4.6-mm 15-cm; packing L11
Flow rate: 1.5 mL/min
Injection size: 10 L for Standard solution 1 and 30 L
for Standard solution 2 and 3
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solutions 1, 2 and 3 and the Sample
solution
Calculate the percentage of C32H39NO4 HCl dissolved:
Result = (rU/rS) (CS/L) F 100
rU = peak area from the Sample solution
rS = peak area from the Standard solution
CS = concentration of the appropriate Standard
solution (mg/mL)
F = volume of Medium (900 mL)
L = Tablet label claim (mg)
Tolerances: NLT 75% (Q) of the labeled amount of
C32H39NO4 HCl is dissolved.
UNIFORMITY OF DOSAGE UNITS 905: Meet the requirements
IMPURITIES
Organic Impurities
PROCEDURE
Solution A, Solution B, Diluent, and Mobile phase:
Prepare as directed in the Assay.
Standard stock solution: Use the Standard stock solution
under Assay.
Standard solution: 0.015 mg/mL of fexofenadine
hydrochloride and 0.0045 mg/mL of fexofenadine related
compound A from Quantitative limit solution and the
Standard stock solution in Mobile phase
Sample stock solution: Use the Sample stock solution
under Assay.
Sample solution: Use the Sample solution under Assay.
System suitability stock solution: Dilute 4.0 mL of the
Standard stock solution, prepared as directed in the Assay,
with Mobile phase to 100 mL.
System suitability solution: Dilute 6.0 mL of the System
suitability stock solution with Mobile phase to 100 mL.
Quantitative limit solution: 0.05 mg/mL of USP
Fexofenadine Related Compound A RS in Diluent
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 220 nm
Column: 4.6-mm 25-cm; 5-m packing L11
Temperature: 35
Flow rate: 1.5 mL/min
Injection size: 20 L
System suitability
Samples: Standard solution and System suitability solution
[NOTEFor the relative retention times, see Impurity Table
1.]
Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
Official Monographs / Fexofenadine 43
Suitability requirements
Resolution: NLT 7 between fexofenadine and
fexofenadine related compound A, Standard solution
Tailing factor: NMT 2.0, Standard solution
Relative standard deviation: NMT 6.0%, System
suitability solution; NMT 2.0% and NMT 3.0% for
fexofenadine and fexofenadine related compound A,
Standard solution
Analysis
Samples: Standard solution, Sample stock solution, and
Sample solution
Calculate the percentage of fexofenadine related
compound A in the portion of Tablets taken:
Result = (rU/rS) C D 100/N L
rU = peak area response of fexofenadine related
compound A in the Sample stock solution
rS = peak area response of fexofenadine related
compound A in the Standard solution
C = concentration of fexofenadine related
compound A in the Standard solution (mg/mL)
D = dilution factor for the Sample stock solution (mL)
N = number of Tablets used to prepare the Sample
stock solution
L = label claim of fexofenadine hydrochloride
(mg/Tablet)
Calculate the percentage of the decarboxylated degradant
[(+)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-
piperidinyl]-butyl]-isopropylbenzene], with a relative
retention time of 6.7, in the portion of Tablets taken:
Result = (rU/rS) C D 100/N L RRF
rU = peak area response of the decarboxylated
degradant in the Sample stock solution
rS = peak area response of fexofenadine in the
Standard solution
C = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
(mg/mL)
D = dilution factor for the Sample stock solution (mL)
N = number of Tablets used to prepare the Sample
stock solution
L = label claim of fexofenadine hydrochloride
(mg/Tablet)
RRF = relative response factor (F is 1.1) for the
decarboxylated degradant (F is 1.0 for all
other known and unknown impurities)
Calculate the percentage of any other impurities in the
portion of Tablets taken:
Result = rU/(D rS + rT) 100
rU = individual peak area response for an individual
unknown impurity in the Sample stock solution
D = dilution factor of the Sample solution (mL)
rS = peak area response for fexofenadine in the
Sample solution
44 Fexofenadine / Official Monographs
rT = sum of the peak area responses of all unknown
impurities in the Sample stock solution
[NOTEDisregard any peak below 0.05%.]
Acceptance criteria
Individual impurities: See Impurity Table 1.
Total impurities: NMT 0.5%
Impurity Table 1
Relative Relative Acceptance
Retention Response Criteria,
Name Time Factor NMT (%)
Fexofenadine related 1.6 0.4
compound A
Decarboxylated 1.1 0.15
degradant
Fexofenadine 1.0
Any individual other 1.0 0.2
impurity
ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in well-closed containers,
and store at controlled room temperature.
LABELING: When more than one Dissolution test is given, the
labeling states the test used only if Test 1 is not used.
USP REFERENCE STANDARDS 11
USP Fexofenadine Hydrochloride RS
USP Fexofenadine Related Compound A RS
Fexofenadine Hydrochloride and
Pseudoephedrine Hydrochloride
Extended-Release Tablets
(Comment on this Monograph)id=m33077=Fexofenadine
Hydrochloride and Pseudoephedrine Hydrochloride Extended-
Release Tablets=F-Monos.pdf)
DEFINITION
Fexofenadine Hydrochloride and Pseudoephedrine
Hydrochloride Extended-Release Tablets contain NLT 95.0%
and NMT 105.0% of the labeled amounts of fexofenadine
hydrochloride (C32H39NO4 HCl) and pseudoephedrine
hydrochloride (C10H15NO HCl).
IDENTIFICATION
A. INFRARED ABSORPTION 197K (for bilayer tablets)
Fexofenadine Hydrochloride
Standard: Transfer a quantity, in mg, of USP Fexofenadine
Hydrochloride RS, equivalent to the labeled amount of
fexofenadine hydrochloride, to a 30-mL capped centrifuge
tube, and add 20 mL of 1 N sodium hydroxide, mix in a
vortex mixer for 1 to 2 min, then centrifuge for 35 min at
2500 rpm or greater. Decant the solution, and pass
through a 25-mm glass syringe filter. Add 10 mL of 10%
hydrochloric acid, and heat this solution, with stirring, to
near boiling. Cool, and centrifuge for 35 min. Decant and
discard the liquid, wash the precipitate with 10 mL of
water, and centrifuge for 12 min. Decant and discard the
water, and dry the precipitate in an oven for 1 h at 105.
Sample: Grind the fexofenadine hydrochloride layer of 1
Tablet, and transfer it into a 30-mL capped centrifuge tube.
Add 20 mL of 1 N sodium hydroxide, mix in a vortex mixer
for 12 min, then centrifuge for 35 min at 2500 rpm or
greater. Decant the solution, and pass through a 25-mm
glass syringe filter. Add 10 mL of 10% hydrochloric acid,
and heat this solution, with stirring, to near boiling. Cool,
and centrifuge for 35 min. Decant and discard the liquid,
wash the precipitate with 10 mL of water, and centrifuge
Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
USP 32
for 12 min. Decant and discard the water, and dry the
precipitate in an oven for 1 h at 105.
Pseudoephedrine Hydrochloride
Standard: Transfer a quantity, in mg, of USP
Pseudoephedrine Hydrochloride RS, equivalent to the
labeled amount of pseudoephedrine hydrochloride, to a
30-mL capped centrifuge tube, and add 20 mL of 0.1 N
hydrochloric acid, mix on a vortex mixer for 12 min, and
centrifuge for 35 min at 2500 rpm or greater. Decant the
solution, and pass through a 0.45-m nylon filter; discard
the residue. Add 10 mL of 1 N sodium hydroxide, and
pour it into a separatory funnel containing 15 mL of
methylene chloride. Carefully rotate and shake the funnel
using care not to form an emulsion. Allow the layers to
separate for about 10 min. Decant the methylene chloride
(lower) layer into a 50-mL beaker, and filter through a glass
funnel loaded with a glass wool plug and 12 g of sodium
sulfate. Evaporate to dryness. [NOTENMT 75 if a hot
plate is used to aid evaporation.]
Sample: Grind the pseudoephedrine hydrochloride layer of
1 Tablet, and transfer it into a capped 30-mL centrifuge
tube. Add 20 mL of 0.1 N hydrochloric acid, mix on a
vortex mixer for 12 min, and centrifuge for 35 min at
2500 rpm or greater. Decant the solution, and pass
through a 0.45-m nylon filter; discard the residue. Add 10
mL of 1 N sodium hydroxide, and pour it into a separatory
funnel containing 15 mL of methylene chloride. Carefully
rotate and shake the funnel using care not to form an
emulsion. Allow the layers to separate for about 10 min.
Decant the methylene chloride (lower) layer into a 50-mL
beaker, and filter through a glass funnel loaded with a glass
wool plug and 12 g of sodium sulfate. Evaporate to
dryness. [NOTENMT 75 if a hot plate is used to aid
evaporation.]
B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
Change to read:
C. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST 201
4
Standard solution A: 6 mg/mL of USP Fexofenadine
Hydrochloride RS in methanol
Standard solution B: 12 mg/mL of USP Pseudoephedrine
Hydrochloride RS in methanol
Sample solution: Transfer the equivalent of 30 mg of
fexofenadine hydrochloride and 60 mg of pseudoephedrine
hydrochloride from finely powdered Tablets (NLT 4) into a
suitable vessel, and add 5 mL of methanol. Cap the vessel,
and shake vigorously for 2 min. Pass the resulting
suspension through a suitable 0.45-m filter. Use the filtrate.
Adsorbent: 0.2-mm layer of high-performance thin-layer
chromatographic silica gel mixture. Dry the plate at 105 for
1 h before use.
Application volume: 10 L
Developing solvent system: Toluene, dehydrated alcohol,
and ammonium hydroxide (50:45:5)
Analysis: Proceed as directed, using the Developing solvent
system. After removal of the plate, mark the solvent front,
and allow the plate to air-dry. Heat the plate at 105 until
the odor of ammonia disappears (about 5 min). Allow the
plate to cool, and examine under UV light at 254 nm.
[NOTEThe RF values are for fexofenadine and
pseudoephedrine are about 0.17 and 0.39, respectively.]
Acceptance criteria: The RF value of fexofenadine
hydrochloride in the Sample solution is comparable to that of
fexofenadine hydrochloride in Standard solution A. The RF
value of pseudoephedrine hydrochloride in the Sample