38 Ferumoxsil / Official Monographs USP 32

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

Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination
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 USP 32

Fexofenadine Hydrochloride Capsules rU = peak response from the Sample solution

(Comment on this Monograph)id=m33075=Fexofenadine rS = peak response from the Standard solution
Hydrochloride Capsules=F-Monos.pdf) CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
DEFINITION (mg/mL)
Fexofenadine Hydrochloride Capsules contain NLT 93.0% and CU = nominal concentration of fexofenadine
NMT 105.0% of the labeled amount of fexofenadine hydrochloride in the Sample solution (mg/mL)
hydrochloride (C32H39NO4 HCl). Acceptance criteria: 93.0%105.0%

IDENTIFICATION PERFORMANCE TESTS

A. The retention time of the major peak in the Sample DISSOLUTION 711
solution corresponds to that of the Standard solution, as TEST 1
obtained in the Assay. Medium: Water; 900 mL
B. INFRARED ABSORPTION 197K Apparatus 2: 50 rpm
Sample solution: Empty an equivalent to 60 mg of Time: 15 and 45 min
fexofenadine hydrochloride, from the contents of several Determine the amount of C32H39NO4 HCl dissolved by
Capsules, into a suitable capped tube. Add 10 mL of a employing the following method.
mixture of acetonitrile and methanol (10:1), and shake until Solution A: 1.0 g of monobasic sodium phosphate, 0.5 g
the sample is dispersed. Allow to settle. Decant, filter, and of sodium perchlorate, and 0.3 mL of phosphoric acid in
collect the supernatant in a suitable beaker. Evaporate the 300 mL of water
solvent to near dryness by using a stream of nitrogen and Mobile phase: Acetonitrile and Solution A (7:3)
with gentle heating from an appropriate source (steam, low- System suitability stock solution: 0.44 mg/mL of USP
temperature hot plate). While still warm, add 5 mL of water Fexofenadine Related Compound A RS in water [NOTEA
and 5 drops of diluted hydrochloric acid, and stir to induce small amount of glacial acetic acid, not to exceed 5% of
precipitation. Chill in an ice bath for about 30 min. Pass the total volume, is used, if necessary, to dissolve USP
through a 10- to 15-m filtering crucible with fritted disk. Fexofenadine Related Compound A RS.]
Dry the precipitate in an air oven for 1 h at 105. System suitability solution: USP Fexofenadine
Hydrochloride RS in System suitability stock solution
ASSAY containing 0.01 mg/mL of USP Fexofenadine Related
PROCEDURE Compound A RS and 0.06 mg/mL of USP Fexofenadine
Solution A: 6.64 g/L of monobasic sodium phosphate and Hydrochloride RS
0.84 g/L of sodium perchlorate in water, and adjust with Standard solution: 0.07 mg/mL of USP Fexofenadine
phosphoric acid to a pH of 2.0 Hydrochloride RS in water [NOTEA small amount of
Diluent: Acetonitrile and Solution A (1:1) methanol, not to exceed 0.5% of the total volume, is used,
Mobile phase: Acetonitrile and Solution A (7:13) if necessary, to dissolve USP Fexofenadine Hydrochloride
[NOTEAdd 3 mL of triethylamine/L in Mobile phase.] RS.]
Standard solution: 0.06 mg/mL of USP Fexofenadine Sample solution: Sample per Dissolution 711. Dilute with
Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine Medium to a concentration that is similar to the Standard
Related Compound A RS in Mobile phase solution.
Sample stock solution: Remove, as completely as possible, Chromatographic system
the contents of NLT 20 Capsules, mix the combined (See Chromatography 621, System Suitability.)
contents, and finely powder by using a mortar and pestle. Mode: LC
Shake by mechanical means for 60 min. Transfer a portion Detector: UV 220 nm
of the powder equivalent to 50 mg of fexofenadine Column: 4.6-mm 10-cm; packing L1
hydrochloride in 40 mL of Diluent. Sonicate for about 2 min. Flow rate: 1 mL/min
Allow to cool to room temperature, and dilute with Diluent Injection size: 50 L
solution to 50 mL. System suitability
Sample solution: Transfer 3.0 mL of the Sample stock Samples: System suitability solution and Standard solution
solution to a 50-mL volumetric flask, and dilute with Mobile Suitability requirements
phase to volume. Resolution: NLT 2.0 between fexofenadine and
Chromatographic system fexofenadine related compound A, System suitability
(See Chromatography 621, System Suitability.) solution
Mode: LC Relative standard deviation: NMT 2.0%, Standard
Detector: UV 220 nm solution
Column: 4.6-mm 25-cm; packing L11 Analysis
Flow rate: 1.5 mL/min Samples: Standard solution and Sample solution
Injection size: 20 L Calculate the quantity of C32H39NO4 HCl dissolved:
System suitability Tolerances: NLT 50% (Q) of the labeled amount of
Sample: Standard solution C32H39NO4 HCl is dissolved in 15 min; NLT 75% (Q) of
Suitability requirements the labeled amount of C32H39NO4 HCl is dissolved in 45
Resolution: NLT 10 between fexofenadine and min.
fexofenadine related compound A TEST 2
Tailing factor: NMT 2.0 If the product complies with this test, the labeling indicates
Relative standard deviation: NMT 2.0% and 3.0% from that the product meets USP Dissolution Test 2.
fexofenadine and fexofenadine related compound A Medium, Apparatus, Solution A, Mobile phase, System
Analysis suitability stock solution, System suitability solution,
Samples: Standard solution and Sample solution Chromatographic system, and Analysis: Proceed as
Calculate the percentage of C32H39NO4 HCl in the portion directed for Test 1.
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 Official Monographs / Fexofenadine 41

Time: 45 min CS = concentration of fexofenadine in the Reference

Tolerances: NLT 75% (Q) of the labeled amount of C32 H39 solution (mg/mL)
NO4 HCl is dissolved. CU = nominal concentration of fexofenadine in the
UNIFORMITY OF DOSAGE UNITS 905: Meet the requirements Sample solution (mg/mL)
Acceptance criteria
IMPURITIES Individual impurities: See Impurity Table 1.
Organic Impurities Total impurities: NMT 0.5%
PROCEDURE
Solution A: 6.64 mg/mL of monobasic sodium phosphate
Impurity Table 1
and 0.84 mg/mL of sodium perchlorate in water, and
adjust with phosphoric acid to a pH of 2.0 Acceptance
Diluent: Acetonitrile and Solution A (1:1) Criteria, NMT
Mobile phase: Acetonitrile and Solution A (7:13) Name (%)
[NOTEAdd 3 mL of triethylamine/L in Mobile phase.] Fexofenadine related compound A 0.4
Standard solution: 0.06 mg/mL of USP Fexofenadine
Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine Decarboxylated degradant 0.2
Related Compound A RS in Mobile phase Any other unknown individual impurity 0.2
Sample solution: 1.0 mg/mL of fexofenadine
hydrochloride in Diluent
Reference solution: 0.06 mg/mL from Sample solution in ADDITIONAL REQUIREMENTS
Mobile phase PACKAGING AND STORAGE: Preserve in tight, light-resistant
Chromatographic system containers. Store at controlled room temperature.
(See Chromatography 621, System Suitability.) LABELING: When more than one Dissolution test is given, the
Mode: LC labeling states the test used only if Test 1 is not used.
Detector: UV 220 nm USP REFERENCE STANDARDS 11
Column: 4.6-mm 25-cm; packing L11 USP Fexofenadine Hydrochloride RS
Flow rate: 1.5 mL/min USP Fexofenadine Related Compound A RS
Injection size: 20 L
Analysis
Samples: Standard solution and Sample solution Fexofenadine Hydrochloride Tablets
Calculate the percentage of fexofenadine related
compound A in the portion of Capsules taken: (Comment on this Monograph)id=m852=Fexofenadine
Hydrochloride Tablets=F-Monos.pdf)
Result = (rU/rS) (CS/CU) 100
DEFINITION
rU = peak response for fexofenadine related Fexofenadine Hydrochloride Tablets contain NLT 95.0% and
compound A from the Sample solution NMT 105.0% of the labeled amount of fexofenadine
rS = peak response for fexofenadine related hydrochloride (C32H39NO4 HCl).
compound A from the Standard solution
CS = concentration of USP Fexofenadine Related IDENTIFICATION
Compound A RS in the Standard solution A. INFRARED ABSORPTION 197K
(mg/mL) Standard solution: Transfer an equivalent to 60 mg of USP
CU = nominal concentration of fexofenadine in the Fexofenadine Hydrochloride RS, from a sufficient number of
Sample solution (mg/mL) weighed and finely powdreed Tablets, to a capped Sample
Calculate the percentage of decarboxylated degradant tube in 10 mL of a mixture of acetonitrile and methanol
[(+)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1- (10:1).
piperidinyl]-butyl]-isopropylbenzene], with a relative Sample solution: Transfer an equivalent to 60 mg of
retention time of 3.2, in the portion of Fexofenadine fexofenadine hydrochloride, from a sufficient number of
Hydrochloride taken: weighed and finely powdered Tablets, to a capped tube, in
10 mL of a mixture of acetonitrile and methanol (10:1).
Result = (rU/rS) (CS/CU) 1/F 100 Analysis: Shake or mix the Standard solution and Sample
solution on a vortex mixer for 12 min to disperse the
rU = peak response of the decarboxylated degradant sample. Allow the solution to stand for 10 min or centrifuge
from the Sample solution for 23 min. Pass the liquid into a 50-mL beaker using a
rS = peak response of fexofenadine from the 0.45-m polytetrafluorethlyene syringe filter. Evaporate the
Standard solution solvent until about 0.5 mL remains using a stream of
CS = concentration of USP Fexofenadine nitrogen with gentle heating (do not exceed 75). Add 5 mL
Hydrochloride RS in the Standard solution of water and 5 drops of dilute hydrochloric acid, and stir to
(mg/mL) induce precipitation. Chill in an ice bath for 30 min. Filter
CU = nominal concentration of fexofenadine in the the solution through a 10- to 15-m sintered-glass crucible.
Sample solution (mg/mL) Dry the precipitate in an air oven for 1 h at 105.
F = response factor for the decarboxylated Acceptance criteria: The IR absorption spectrum of a
degradant relative to fexofenadine, 1.1 potassium bromide dispersion of the residue exhibits
Calculate the percentage of other impurities in the portion maxima only at the same wavelengths as that of a
of Fexofenadine Hydrochloride taken: potassium bromide dispersion of a similar solution using USP
Fexofenadine Hydrochloride RS.
Result = (rU/rS) (CS/CU) 100 B. The retention time of the major peak in the Sample
solution corresponds to that of the Standard solution, as
rU = peak response for any other impurity from the obtained in the Assay.
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
42 Fexofenadine / Official Monographs USP 32

ASSAY Mobile phase: Acetonitrile and Solution A (7:3)

PROCEDURE Standard solution: USP Fexofenadine Hydrochloride RS in
Solution A: Glacial acetic acid and water (17:1000). Dilute Medium to obtain a solution having a known concentration
100 mL of this solution with water to 1 L. similar to that expected for the solution under test
Solution B: Dilute 15 mL of a solution containing [NOTEA small amount of methanol, not exceeding 0.5%
acetonitrile and triethylamine (1:1) with Solution A to 1 L. of the total volume, can be used to dissolve fexofenadine
Adjust with phosphoric acid to a pH of 5.25. hydrochloride.]
Diluent: Acetonitrile and Solution A (3:1) System suitability solution: 0.44 mg/mL of USP
Mobile phase: Acetonitrile and Solution B (9:16) Fexofenadine Related Compound A RS in water. Transfer
Standard stock solution: 0.25 mg/mL of USP Fexofenadine 1.0 mL of this solution into a vial, and add 40 mL of the
Hydrochloride RS in Diluent Standard solution.
Standard solution: 0.015 mg/mL from Standard stock [NOTEA small amount of acetic acid, not exceeding 5% of
solution in Mobile phase the total volume, can be used to dissolve fexofenadine
Sample stock solution: Transfer a sufficient number of hydrochloride related compound A.]
whole Tablets (NLT 10) to a suitable volumetric flask, add Sample solution: Sample per Dissolution 711. Dilute with
Solution A (equivalent to 20% of the total flask volume), and Medium to concentration that is similar to the Standard
shake by mechanical means at a high speed for 30 min or solution. Use portions of the solution under test passed
until the Tablets are fully disintegrated and finely dispersed. through a 0.45-m glass fiber filter.
Add acetonitrile (equivalent to 80% of the total flask Chromatographic system
volume), and shake by mechanical means for 60 min. Dilute (See Chromatography 621, System Suitability.)
with Diluent to volume. Pass a portion of this solution Mode: LC
through a polytetrafluorethylene filter having a 0.45-m or Detector: UV 220 nm
finer porosity, and use the filtrate. Dilute, if necessary, with Column: 4.6-mm 10-cm; packing L1
Diluent to obtain a solution containing an equivalent to 1.2 Flow rate: 1 mL/min
mg/mL of fexofenadine hydrochloride. Injection size: 23 g column load of fexofenadine
Sample solution: 0.018 mg/mL from Sample stock solution hydrochloride
in Mobile phase System suitability
Chromatographic system Samples: Standard solution and System suitability solution
(See Chromatography 621, System Suitability.) Suitability requirements
Mode: LC Resolution: NLT 2.0 between fexofenadine and
Detector: UV 220 nm fexofenadine related compound A, System suitability
Column: 4.6-mm 25-cm; 5-m packing L11 solution
Temperature: 35 Relative standard deviation: NMT 2.0%, Standard
Flow rate: 1.5 mL/min solution
Injection size: 20 L Analysis
System suitability Samples: Standard solution and Sample solution
Sample: Standard solution Calculate the percentage of C32H39NO4 HCl dissolved in
Suitability requirements the Medium:
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0% Result = (rU/rS) (CS/CU) 100
Analysis
Samples: Standard solution and Sample solution rU = peak area from the Sample solution
Calculate the percentage of C32H39NO4 HCl in the portion rS = peak area from the Standard solution
of Tablets taken: CS = concentration of USP Fexofenadine
Hydrochloride RS in the Standard solution
Result = (rU/rS) (CS/CU) 100 (mg/mL)
CU = nominal concentration of fexofenadine
rU = peak response from the Sample solution hydrochloride in the Sample solution (mg/mL)
rS = peak response from the Standard solution Tolerances: NLT 60% (Q) of the labeled amount of C32H39
CS = concentration of USP Fexofenadine NO4 HCl is dissolved in 10 min; NLT 80% (Q) of the
Hydrochloride RS in the Standard solution labeled amount of C32 H39 NO4 HCl is dissolved in 30 min.
(mg/mL) TEST 2
CU = nominal concentration of fexofenadine Medium: 0.001 N hydrochloric acid; 900 mL
hydrochloride in the Sample solution (mg/mL) Apparatus 2: 50 rpm, use paddles and shafts coated with
Acceptance criteria: 95.0%105.0% Teflon.
Time: 30 min
PERFORMANCE TESTS Determine the percentages of the labeled amount of
DISSOLUTION 711 C32H39NO4 HCl dissolved by using the following method.
TEST 1 Solution A: 7 mg/mL of ammonium acetate in water.
Medium: 0.001 N hydrochloric acid; 900 mL Adjust with glacial acetic acid to a pH of 4.0 0.05.
Apparatus 2: 50 rpm Mobile phase: Acetonitrile and Solution A (2:3)
Time: 10 and 30 min Standard solution 1: Transfer 20 mg of USP Fexofenadine
Determine the percentages of the labeled amount of Hydrochloride RS to a 100-mL volumetric flask. Add 3.0 mL
C32H39NO4 HCl dissolved by using the following method. of methanol, and mix. Dilute with Medium to volume.
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 Official Monographs / Fexofenadine 43

Standard solution 2: Transfer 15.0 mL of Standard solution Suitability requirements

1 to a 50-mL volumetric flask. Dilute with Medium to Resolution: NLT 7 between fexofenadine and
volume. fexofenadine related compound A, Standard solution
Standard solution 3: Transfer 7.5 mL of Standard solution Tailing factor: NMT 2.0, Standard solution
1 to a 50-mL volumetric flask. Dilute with Medium to Relative standard deviation: NMT 6.0%, System
volume. suitability solution; NMT 2.0% and NMT 3.0% for
Sample solution: Sample per Dissolution 711. Use fexofenadine and fexofenadine related compound A,
portions of the solution under test passed through a Standard solution
suitable 0.45-m filter. Analysis
Chromatographic system Samples: Standard solution, Sample stock solution, and
(See Chromatography 621, System Suitability.) Sample solution
Mode: LC Calculate the percentage of fexofenadine related
Detector: UV 259 nm compound A in the portion of Tablets taken:
Column: 4.6-mm 15-cm; packing L11
Flow rate: 1.5 mL/min Result = (rU/rS) C D 100/N L
Injection size: 10 L for Standard solution 1 and 30 L
for Standard solution 2 and 3 rU = peak area response of fexofenadine related
System suitability compound A in the Sample stock solution
Sample: Standard solution rS = peak area response of fexofenadine related
Suitability requirements compound A in the Standard solution
Tailing factor: NMT 2.0 C = concentration of fexofenadine related
Relative standard deviation: NMT 2.0% compound A in the Standard solution (mg/mL)
Analysis D = dilution factor for the Sample stock solution (mL)
Samples: Standard solutions 1, 2 and 3 and the Sample N = number of Tablets used to prepare the Sample
solution stock solution
Calculate the percentage of C32H39NO4 HCl dissolved: L = label claim of fexofenadine hydrochloride
(mg/Tablet)
Result = (rU/rS) (CS/L) F 100 Calculate the percentage of the decarboxylated degradant
[(+)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-
rU = peak area from the Sample solution piperidinyl]-butyl]-isopropylbenzene], with a relative
rS = peak area from the Standard solution retention time of 6.7, in the portion of Tablets taken:
CS = concentration of the appropriate Standard
solution (mg/mL) Result = (rU/rS) C D 100/N L RRF
F = volume of Medium (900 mL)
L = Tablet label claim (mg) rU = peak area response of the decarboxylated
Tolerances: NLT 75% (Q) of the labeled amount of degradant in the Sample stock solution
C32H39NO4 HCl is dissolved. rS = peak area response of fexofenadine in the
UNIFORMITY OF DOSAGE UNITS 905: Meet the requirements Standard solution
C = concentration of USP Fexofenadine
IMPURITIES Hydrochloride RS in the Standard solution
Organic Impurities (mg/mL)
PROCEDURE D = dilution factor for the Sample stock solution (mL)
Solution A, Solution B, Diluent, and Mobile phase: N = number of Tablets used to prepare the Sample
Prepare as directed in the Assay. stock solution
Standard stock solution: Use the Standard stock solution L = label claim of fexofenadine hydrochloride
under Assay. (mg/Tablet)
Standard solution: 0.015 mg/mL of fexofenadine RRF = relative response factor (F is 1.1) for the
hydrochloride and 0.0045 mg/mL of fexofenadine related decarboxylated degradant (F is 1.0 for all
compound A from Quantitative limit solution and the other known and unknown impurities)
Standard stock solution in Mobile phase Calculate the percentage of any other impurities in the
Sample stock solution: Use the Sample stock solution portion of Tablets taken:
under Assay.
Sample solution: Use the Sample solution under Assay. Result = rU/(D rS + rT) 100
System suitability stock solution: Dilute 4.0 mL of the
Standard stock solution, prepared as directed in the Assay, rU = individual peak area response for an individual
with Mobile phase to 100 mL. unknown impurity in the Sample stock solution
System suitability solution: Dilute 6.0 mL of the System D = dilution factor of the Sample solution (mL)
suitability stock solution with Mobile phase to 100 mL. rS = peak area response for fexofenadine in the
Quantitative limit solution: 0.05 mg/mL of USP Sample solution
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
44 Fexofenadine / Official Monographs USP 32

rT = sum of the peak area responses of all unknown for 12 min. Decant and discard the water, and dry the
impurities in the Sample stock solution precipitate in an oven for 1 h at 105.
[NOTEDisregard any peak below 0.05%.] Pseudoephedrine Hydrochloride
Acceptance criteria Standard: Transfer a quantity, in mg, of USP
Individual impurities: See Impurity Table 1. Pseudoephedrine Hydrochloride RS, equivalent to the
Total impurities: NMT 0.5% labeled amount of pseudoephedrine hydrochloride, to a
30-mL capped centrifuge tube, and add 20 mL of 0.1 N
Impurity Table 1 hydrochloric acid, mix on a vortex mixer for 12 min, and
centrifuge for 35 min at 2500 rpm or greater. Decant the
Relative Relative Acceptance solution, and pass through a 0.45-m nylon filter; discard
Retention Response Criteria, the residue. Add 10 mL of 1 N sodium hydroxide, and
Name Time Factor NMT (%) pour it into a separatory funnel containing 15 mL of
Fexofenadine related 1.6 0.4 methylene chloride. Carefully rotate and shake the funnel
compound A using care not to form an emulsion. Allow the layers to
Decarboxylated 1.1 0.15
separate for about 10 min. Decant the methylene chloride
degradant
(lower) layer into a 50-mL beaker, and filter through a glass
funnel loaded with a glass wool plug and 12 g of sodium
Fexofenadine 1.0 sulfate. Evaporate to dryness. [NOTENMT 75 if a hot
Any individual other 1.0 0.2 plate is used to aid evaporation.]
impurity 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
ADDITIONAL REQUIREMENTS vortex mixer for 12 min, and centrifuge for 35 min at
PACKAGING AND STORAGE: Preserve in well-closed containers, 2500 rpm or greater. Decant the solution, and pass
and store at controlled room temperature. through a 0.45-m nylon filter; discard the residue. Add 10
LABELING: When more than one Dissolution test is given, the mL of 1 N sodium hydroxide, and pour it into a separatory
labeling states the test used only if Test 1 is not used. funnel containing 15 mL of methylene chloride. Carefully
USP REFERENCE STANDARDS 11 rotate and shake the funnel using care not to form an
USP Fexofenadine Hydrochloride RS emulsion. Allow the layers to separate for about 10 min.
USP Fexofenadine Related Compound A RS 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
Fexofenadine Hydrochloride and evaporation.]
Pseudoephedrine Hydrochloride B. The retention time of the major peak of the Sample
Extended-Release Tablets solution corresponds to that of the Standard solution, as
(Comment on this Monograph)id=m33077=Fexofenadine obtained in the Assay.
Hydrochloride and Pseudoephedrine Hydrochloride Extended-
Release Tablets=F-Monos.pdf) Change to read:
DEFINITION
Fexofenadine Hydrochloride and Pseudoephedrine C. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST 201
Hydrochloride Extended-Release Tablets contain NLT 95.0% 4
and NMT 105.0% of the labeled amounts of fexofenadine Standard solution A: 6 mg/mL of USP Fexofenadine
hydrochloride (C32H39NO4 HCl) and pseudoephedrine Hydrochloride RS in methanol
hydrochloride (C10H15NO HCl). Standard solution B: 12 mg/mL of USP Pseudoephedrine
IDENTIFICATION Hydrochloride RS in methanol
A. INFRARED ABSORPTION 197K (for bilayer tablets) Sample solution: Transfer the equivalent of 30 mg of
Fexofenadine Hydrochloride fexofenadine hydrochloride and 60 mg of pseudoephedrine
Standard: Transfer a quantity, in mg, of USP Fexofenadine hydrochloride from finely powdered Tablets (NLT 4) into a
Hydrochloride RS, equivalent to the labeled amount of suitable vessel, and add 5 mL of methanol. Cap the vessel,
fexofenadine hydrochloride, to a 30-mL capped centrifuge and shake vigorously for 2 min. Pass the resulting
tube, and add 20 mL of 1 N sodium hydroxide, mix in a suspension through a suitable 0.45-m filter. Use the filtrate.
vortex mixer for 1 to 2 min, then centrifuge for 35 min at Adsorbent: 0.2-mm layer of high-performance thin-layer
2500 rpm or greater. Decant the solution, and pass chromatographic silica gel mixture. Dry the plate at 105 for
through a 25-mm glass syringe filter. Add 10 mL of 10% 1 h before use.
hydrochloric acid, and heat this solution, with stirring, to Application volume: 10 L
near boiling. Cool, and centrifuge for 35 min. Decant and Developing solvent system: Toluene, dehydrated alcohol,
discard the liquid, wash the precipitate with 10 mL of and ammonium hydroxide (50:45:5)
water, and centrifuge for 12 min. Decant and discard the Analysis: Proceed as directed, using the Developing solvent
water, and dry the precipitate in an oven for 1 h at 105. system. After removal of the plate, mark the solvent front,
Sample: Grind the fexofenadine hydrochloride layer of 1 and allow the plate to air-dry. Heat the plate at 105 until
Tablet, and transfer it into a 30-mL capped centrifuge tube. the odor of ammonia disappears (about 5 min). Allow the
Add 20 mL of 1 N sodium hydroxide, mix in a vortex mixer plate to cool, and examine under UV light at 254 nm.
for 12 min, then centrifuge for 35 min at 2500 rpm or [NOTEThe RF values are for fexofenadine and
greater. Decant the solution, and pass through a 25-mm pseudoephedrine are about 0.17 and 0.39, respectively.]
glass syringe filter. Add 10 mL of 10% hydrochloric acid, Acceptance criteria: The RF value of fexofenadine
and heat this solution, with stirring, to near boiling. Cool, hydrochloride in the Sample solution is comparable to that of
and centrifuge for 35 min. Decant and discard the liquid, fexofenadine hydrochloride in Standard solution A. The RF
wash the precipitate with 10 mL of water, and centrifuge value of pseudoephedrine hydrochloride in the Sample

Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination