Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets contain NLT 93.0% and NMT 107.0% of the labeled amounts of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl).

2 IDENTIFICATION

Change to read:

A. The retention times of the fexofenadine and pseudoephedrine (IRA 1-Nov-2024) peaks of the Sample solution correspond to those of the

Standard solution, as obtained in the Assay.

Change to read:

B. Thin-Layer Chromatographic Identification Test 〈201〉

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: Nominally 6 mg/mL of fexofenadine hydrochloride and 12 mg/mL of pseudoephedrine hydrochloride from Tablets prepared as follows. (IRA 1-Nov-2024) 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 filter of 0.45-μm pore size. Use the filtrate.

Adsorbent: 0.2-mm layer of HPTLC silica gel mixture. Dry the plate at 105° for 1 h before use.

Application volume: 10 μL

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.

[Note-The R values for fexofenadine and pseudoephedrine are 0.17 and 0.39, respectively.]

Acceptance criteria: The R value of fexofenadine hydrochloride in the Sample solution is comparable to that of fexofenadine hydrochloride in Standard solution A. The R value of pseudoephedrine hydrochloride in the Sample solution is comparable to that of pseudoephedrine hydrochloride in Standard solution B.

3 ASSAY

Change to read:

3.1 Procedure 1

Buffer: Dissolve 6.8 g of sodium acetate and 16.22 g of sodium 1-octanesulfonate in water, and dilute with water to 1 L. Adjust with glacial acetic acid to a pH of 4.6.

Mobile phase: Methanol and Buffer (65:35) (IRA 1-Nov-2024)

System suitability solution: Transfer 40 mg of USP Pseudoephedrine Hydrochloride RS to a 50-mL volumetric flask. Add 5 mL of tert-butylhydroperoxide solution, and sonicate. Cover the flask opening with aluminum foil, and place the flask in an oven at 90° for 60 min.

Remove from the oven, and allow to cool. Add 35 mL of Mobile phase, and cool to room temperature. Dilute with Mobile phase to volume.

The degradation of pseudoephedrine hydrochloride by this process produces the related compound methcathinone. (IRA 1-Nov-2024)

Related compounds stock solution: 0.2 mg/mL each of USP Fexofenadine Related Compound A RS and USP Fexofenadine Related

Compound C RS prepared as follows. Transfer suitable (IRA 1-Nov-2024) quantities of USP Fexofenadine Related Compound A RS and USP

Fexofenadine Related Compound C RS to a suitable volumetric flask. Dissolve in 65% of the flask volume of methanol and dilute with Buffer to volume. (IRA 1-Nov-2024)

Related compounds solution: 0.02 mg/mL each of USP Fexofenadine Related Compound A RS and USP Fexofenadine Related Compound C RS (IRA 1-Nov-2024) from Related compounds stock solution in (IRA 1-Nov-2024) Mobile phase

Standard stock solution: 0.4 mg/mL of (IRA 1-Nov-2024) USP Fexofenadine Hydrochloride RS and 8 mg/mL of (IRA 1-Nov-2024) USP Pseudoephedrine Hydrochloride RS, (IRA 1-Nov-2024) in Mobile phase

Standard solution: 0.048 mg/mL of USP Fexofenadine Hydrochloride RS and 0.096 mg/mL of USP Pseudoephedrine Hydrochloride RS from the Standard stock solution, and 0.006 mg/mL each of USP Fexofenadine Related Compound A RS and USP Fexofenadine Related Compound C RS from the Related compounds solution in Mobile phase (IRA 1-Nov-2024)

Sample stock solution: Nominally (IRA 1-Nov-2024) 1.2 mg/mL of fexofenadine hydrochloride and 2.4 mg/mL of pseudoephedrine hydrochloride from Tablets prepared as follows. (IRA 1-Nov-2024) Transfer NLT 10 whole Tablets to a 500-mL volumetric flask. Add 300 mL of methanol, and shake by mechanical means at high speed for 60 min. Sonicate the flask for 60 min at 40°. Add 150 mL of Buffer, and sonicate for 60 min at 40°. Vent the flask, and vigorously shake the flask by hand at 15-min intervals during the mechanical shaking and sonication steps. Cool to room temperature, and dilute with Buffer to volume. (IRA 1-Nov-2024) Pass a portion of this solution through a filter of 0.45-μm or finer pore size, and use the filtrate. [Note—Alternatively, centrifuge the Sample stock solution, and use the supernatant to prepare the Sample solution.] (IRA 1-Nov-2024)

Sample solution: Nominally (IRA 1-Nov-2024) 0.048 and 0.096 mg/mL of fexofenadine hydrochloride and pseudoephedrine hydrochloride, respectively, from the Sample stock solution in (IRA 1-Nov-2024) Mobile phase. Filter the Sample solution before analysis. (IRA 1-Nov-2024)

3.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 5-cm; 5-μm packing L6 connected in series to a 4.6-mm × 25-cm; 5-μm packing L11

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

3.1.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for pseudoephedrine and methcathinone (IRA 1-Nov-2024) are 1.0 and 1.2, respectively (System suitability solution); and for fexofenadine, fexofenadine related compound A, and fexofenadine related compound C are (IRA 1-Nov-2024) 1.0, 1.2, and 2.3, (IRA 1-Nov-2024) respectively (Standard solution).]

3.1.3 Suitability requirements

Resolution: NLT 1.5 between pseudoephedrine and methcathinone, (IRA 1-Nov-2024) System suitability solution; NLT 2.0 between fexofenadine and fexofenadine related compound A, Standard solution

Relative standard deviation: NMT 1.0% for (IRA 1-Nov-2024) pseudoephedrine, Standard solution; (IRA 1-Nov-2024) NMT 1.0% for (IRA 1-Nov-2024) fexofenadine (IRA 1-Nov-2024), Standard solution

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate (IRA 1-Nov-2024) the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of (IRA 1-Nov-2024) fexofenadine or pseudoephedrine from the Sample solution

r_S = peak response of (IRA 1-Nov-2024) fexofenadine or pseudoephedrine from the Standard solution

C_S = concentration of (IRA 1-Nov-2024) USP Fexofenadine Hydrochloride RS or USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of (IRA 1-Nov-2024) fexofenadine hydrochloride or pseudoephedrine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

Change to read:

3.2 Procedure 2

Use this procedure for Tablets labeled to meet Dissolution Test 5.

Buffer: Dissolve 6.8 g of sodium acetate and 16.22 g of sodium 1-octanesulfonate in water, and dilute with water to 1 L. Adjust with glacial acetic acid to a pH of 4.0.

Mobile phase: Methanol and Buffer (65:35) (IRA 1-Nov-2024)

System suitability solution: Transfer 60 mg of USP Pseudoephedrine Hydrochloride RS to a 50-mL volumetric flask. Add 10 mL of Hydrogen peroxide, and swirl the flask. Cover the flask opening with aluminum foil, and heat in an oven at 90° for 4 h. Add 35 mL of Mobile phase, and cool to room temperature. Dilute with Mobile phase to volume. The degradation of pseudoephedrine hydrochloride by this process produces the related compound methcathinone. (IRA 1-Nov-2024)

Related compounds stock solution: 0.225 mg/mL each of USP Fexofenadine Related Compound A RS and USP Fexofenadine Related Compound C RS, (IRA 1-Nov-2024) prepared as follows. Transfer suitable quantities of (IRA 1-Nov-2024) USP Fexofenadine Related Compound A RS and USP Fexofenadine Related Compound C RS to a suitable volumetric flask. Dissolve in 65% of the flask volume of methanol and dilute with Buffer to volume. (IRA 1-Nov-2024)

Related compounds solution: 0.0113 mg/mL each of USP Fexofenadine Related Compound A RS and USP Fexofenadine Related Compound C RS (IRA 1-Nov-2024) from Related compounds stock solution in Mobile phase

Standard stock solution: 0.36 mg/mL of USP Fexofenadine Hydrochloride RS and 0.48 mg/mL of USP Pseudoephedrine Hydrochloride RS in Mobile phase

Standard solution: 0.096 mg/mL of USP Pseudoephedrine Hydrochloride RS, 0.072 mg/mL of USP Fexofenadine Hydrochloride RS from the Standard stock solution, (IRA 1-Nov-2024) and 0.002 mg/mL each of USP Fexofenadine Related Compound A RS and USP Fexofenadine Related Compound C RS from the Related compounds solution in Mobile phase (IRA 1-Nov-2024)

Sample stock solution: Nominally (IRA 1-Nov-2024) 0.36 mg/mL of fexofenadine hydrochloride and 0.48 mg/mL of pseudoephedrine hydrochloride from Tablets, (IRA 1-Nov-2024) prepared as follows. Crush NLT 10 Tablets into small pieces in a mortar, transfer the composite to a 500-mL volumetric flask, and add 325 mL of methanol. Shake by mechanical means for at least 30 min, and sonicate for at least an additional 35 min. Add 100 mL of Buffer, sonicate for 45 min, cool to room temperature, and allow to stand for 16 h without mechanical shaking. Dilute with Buffer to volume. Pass a portion of this solution through a suitable filter of 0.45-μm or finer pore size.

Transfer 5 mL of the filtrate to a 50-mL volumetric flask, and dilute with Buffer to volume.

Sample solution: Nominally (IRA 1-Nov-2024) 0.072 and 0.096 mg/mL of fexofenadine hydrochloride and pseudoephedrine hydrochloride, respectively, in Mobile phase, from the Sample stock solution

3.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 5-cm; 5-μm packing L6 connected in series to a 4.6-mm × 25-cm; 5-μm packing L11

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

3.2.2 System suitability

Samples: System suitability solution and Standard solution [Note—The relative retention times for pseudoephedrine and methcathinone are 1.0 and 1.2, respectively, System suitability solution; and for fexofenadine, fexofenadine related compound A, and fexofenadine related compound C are 1.0, 1.2, and 2.3, respectively, Standard solution.] (IRA 1-Nov-2024)

3.2.3 Suitability requirements

Resolution: NLT 2.0 between pseudoephedrine and methcathinone,(IRA 1-Nov-2024) System suitability solution; NLT 2.0 between fexofenadine and fexofenadine related compound A, Standard solution

Relative standard deviation: NMT 1.0% for (IRA 1-Nov-2024) pseudoephedrine, Standard solution; (IRA 1-Nov-2024) NMT 1.0% for (IRA 1-Nov-2024) fexofenadine, (IRA 1-Nov-2024) Standard solution

3.2.4 Analysis

Samples: Standard solution and Sample solution

Calculate (IRA 1-Nov-2024) the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of (IRA 1-Nov-2024) fexofenadine or pseudoephedrine from the Sample solution

r_S = peak response of (IRA 1-Nov-2024) fexofenadine or pseudoephedrine from the Standard solution

C_S = concentration of (IRA 1-Nov-2024) USP Fexofenadine Hydrochloride RS or USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of (IRA 1-Nov-2024) fexofenadine hydrochloride or pseudoephedrine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

3.3 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

3.4 Test 1

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

3.4.1 Times

Fexofenadine hydrochloride: 15 and 45 min

Pseudoephedrine hydrochloride: 45 min; 3, 5, and 12 h

Solution A: 7.0 g/L (IRA 1-Nov-2024) of monobasic sodium phosphate monohydrate in water. Adjust with (IRA 1-Nov-2024) phosphoric acid to a pH of 2.00 ± 0.05.

Mobile phase: Acetonitrile and Solution A (45:55) (IRA 1-Nov-2024)

Standard solution: Dissolve quantities of USP Fexofenadine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS in Medium, and dilute to obtain a solution containing known concentrations similar to those expected in the Sample solution. [Note-A small amount of methanol, NMT 0.5% of the total volume, can be used to dissolve the fexofenadine hydrochloride.]

Sample solution: Pass a portion of the solution under test through a suitable nylon filter of 0.45-μm pore size.

3.4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; packing L6

Flow rate: 1 mL/min

Injection volume: 10 μL

3.4.3 System suitability

Sample: Standard solution

3.4.4 Suitability requirements

Resolution: NLT 3.0 between fexofenadine and pseudoephedrine

Tailing factor: NMT 1.5 for fexofenadine and pseudoephedrine

3.4.5 Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

3.4.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of the labeled amounts of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved.

Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): NLT 65% (Q) of the labeled amount is dissolved in 15 min, and NLT 80% (Q) of the labeled amount is dissolved in 45 min.

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 1.

Table 1

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.5 Test 2

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

3.5.1 Times

Fexofenadine hydrochloride: 45 min

Pseudoephedrine hydrochloride: 30 min; 2, 4, and 12 h

Solution A: 2.7 g/L (IRA 1-Nov-2024) of monobasic potassium phosphate and 2.2 g/L(IRA 1-Nov-2024) of sodium 1-octanesulfonate in water. Adjust with phosphoric acid to a pH of 2.50 ± 0.05.

Mobile phase: Methanol, acetonitrile, and Solution A (30:30:40) (IRA 1-Nov-2024)

Fexofenadine standard stock solution: Transfer 66 mg of USP Fexofenadine Hydrochloride RS to a 100-mL volumetric flask. Add 10 mL of methanol, and swirl until dissolved. Add 50 mL of Medium, and mix. Allow the solution to equilibrate to room temperature, and dilute with Medium to volume.

Pseudoephedrine standard stock solution: Transfer 66 mg of USP Pseudoephedrine Hydrochloride RS to a 100-mL volumetric flask. Add 10 mL of methanol, and swirl until dissolved. Add 50 mL of Medium, and mix. Allow the solution to equilibrate to room temperature, and dilute with Medium to volume.

Standard solution: 66 μg/mL of USP Fexofenadine Hydrochloride RS and 132 μg/mL of USP Pseudoephedrine Hydrochloride RS from (IRA 1-Nov-2024) Fexofenadine standard stock solution and Pseudoephedrine standard stock solution respectively, in (IRA 1-Nov-2024) Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

3.5.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 5-μm packing L7

Flow rate: 1.5 mL/min

Injection volume: 10 μL

3.5.3 System suitability

Sample: Standard solution

3.5.4 Suitability requirements

Resolution: NLT 2.0 between fexofenadine and pseudoephedrine

Tailing factor: NMT 2.0 for fexofenadine and NMT 2.5 for pseudoephedrine

Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

3.5.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of the labeled amounts of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved.

3.5.6 Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): NLT 80% (Q) of the labeled amount is dissolved in 45 min.

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 2.

Table 2

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.6 Test 3

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

3.6.1 Times

Fexofenadine hydrochloride: 30 min

Pseudoephedrine hydrochloride: 30 min; (IRA 1-Nov-2024) 2, 4, and 12 h

Buffer solution: 6.64 g/L of monobasic sodium phosphate in water. Adjust with phosphoric acid to a pH of 2.50 ± 0.05.

Mobile phase: Acetonitrile and Buffer solution (40:60) (IRA 1-Nov-2024)

Standard solution: [Note-A small amount of methanol, not exceeding 0.5% of the final total volume, can be used to dissolve fexofenadine hydrochloride.] Prepare a solution in Medium containing known concentrations of USP Fexofenadine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS similar to those expected in the solution under test.

Sample solution: Pass a portion of the solution under test through a suitable PVDF or nylon filter of 0.45-μm pore size.

3.6.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 2.5 mL/min

Injection volume: 10 μL

3.6.3 System suitability

Sample: Standard solution

3.6.4 Suitability requirements

Tailing factor: NMT 2.0 for fexofenadine and pseudoephedrine

Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

3.6.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of the labeled amounts of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved.

3.6.6 Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): NLT 80% (Q) of the labeled amount is dissolved in 30 min.

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 3.

Table 3

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.7 Test 4

For products labeled with a dosing interval of 24 h. If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 4.

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

3.7.1 Times

Fexofenadine hydrochloride: 30 min

Pseudoephedrine hydrochloride: 3, 7, and 23 h

Determine the percentages of the labeled amounts of fexofenadine hydrochloride and pseudoephedrine hydrochloride dissolved by using the chromatographic procedure described in Test 1.

3.7.2 Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): NLT 80% (Q) of the labeled amount is dissolved in 30 min.

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 4.

Table 4

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.8 Test 5

For products labeled with a dosing interval of 24 h. If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 5.

Medium: 0.001 N hydrochloric acid; 900 mL deaerated

Apparatus 2: 50 rpm, with sinkers1

3.8.1 Times

Fexofenadine hydrochloride: 15 and 45 min

Pseudoephedrine hydrochloride: 3, 7, and 23 h

Buffer: 4.1 g/L of anhydrous sodium acetate in water. Adjust with glacial acetic acid to a pH of 3.6 ± 0.1.

Mobile phase: Methanol and Buffer (60:40)

Standard solution: Prepare a solution in Medium containing 0.20 mg/mL of USP Fexofenadine Hydrochloride RS and 0.27 mg/mL of USP Pseudoephedrine Hydrochloride RS. Sonicate to dissolve.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

3.8.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 10-cm; 5-μm packing L9

Column temperature: 40°

Flow rate: 2 mL/min

Injection volume: 50 μL

3.8.3 System suitability

Sample: Standard solution

[Note-The relative retention times for fexofenadine and pseudoephedrine are 0.45 and 1.0, respectively.]

3.8.4 Suitability requirements

Resolution: NLT 2.0 between fexofenadine and pseudoephedrine

Tailing factor: NMT 2.0 for fexofenadine and pseudoephedrine

Relative standard deviation: NMT 1.5% for fexofenadine and pseudoephedrine

3.8.5 Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) in the sample withdrawn from the vessel at each time point (i) (IRA 1-Nov-2024) :

Result_i = (r_U /r_S ) × C_S

r_U = peak response of fexofenadine from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount  (IRA 1-Nov-2024) of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved at each time point (i) (IRA 1-Nov-2024):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S )] + (C₁ × V_S )} × (1/L) × 100

C_i = concentration of fexofenadine hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim for fexofenadine hydrochloride (mg/Tablet)

V = volume of the Sample solution withdrawn from the Medium (mL)

Calculate the concentration (C_i ) of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the sample withdrawn from the vessel at each time point (i) (IRA 1-Nov-2024) :

Result_i = (r_U /r_S ) × C_S

r_U = peak response of pseudoephedrine from the Sample solution

r_S = peak response of pseudoephedrine from the Standard solution

C_S = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount  (IRA 1-Nov-2024) of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved at each time point (i) (IRA 1-Nov-2024) :

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S )] + (C₁ × V_S )} × (1/L) × 100

Result = ({C₃ × [V₃ − (2 × V_S )]} + [(C₂ + C₁ ) × V_S ]) × (1/L) × 100

C_i = concentration of pseudoephedrine hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim for pseudoephedrine hydrochloride (mg/Tablet)

V_S = volume of the Sample solution withdrawn from the Medium (mL)

Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): See Table 5.

Table 5

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 6.

Table 6

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.9 Test 6

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 6.

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

3.9.1 Times

Fexofenadine hydrochloride: 45 min

Pseudoephedrine hydrochloride: 30 min; 2, 4, and 12 h

Solution A: 7 g/L of monobasic sodium phosphate in water. Adjust with  (IRA 1-Nov-2024) phosphoric acid to a pH of 2.00.

Mobile phase: Acetonitrile and Solution A (45:55)

Standard solution: 0.07 mg/mL of USP Fexofenadine Hydrochloride RS and 0.13 mg/mL of USP Pseudoephedrine Hydrochloride RS, prepared as follows. Dissolve appropriate quantities of USP Fexofenadine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS in a small amount of methanol, NMT 0.8% of the final volume, and add 40% of the final volume of Medium. Sonicate to dissolve and dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

3.9.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 10-μm packing L6

Flow rate: 1 mL/min

Injection volume: 10 μL

3.9.3 System suitability

Sample: Standard solution

3.9.4 Suitability requirements

Resolution: NLT 3.0 between fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

Tailing factor: NMT 2.0 for (IRA 1-Nov-2024) fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

3.9.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved:

Result = (r_U /r_S ) × C_S × V × (1/L) × 100

r_U = peak response of fexofenadine from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim for fexofenadine hydrochloride (mg/Tablet)

Calculate the concentration (C_i) of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the sample withdrawn from the vessel at each time point (i)  (IRA 1-Nov-2024) :

Result_i = (r_U /r_S ) × C_S

r_U = peak response of pseudoephedrine from the Sample solution

r_S = peak response of pseudoephedrine from the Standard solution

C_S = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved at each time point (i) (IRA 1-Nov-2024) :

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S )] + (C₁ × V )} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S )]} + [(C₂ + C_{​​​​​​​1} ) × V_S ]) × (1/L) × 100

Result₄ = ({C₄ × [V − (3 × V_S )]} + [(C₃ + C₂ + C_{​​​​​​​1} ) × V_S ]) × (1/L) × 100

C_i = concentration of pseudoephedrine hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim for pseudoephedrine hydrochloride (mg/Tablet)

V_S = volume of the Sample solution withdrawn from the Medium (mL)

3.9.6 Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): NLT 80% (Q) of the labeled amount is dissolved.

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 7.

Table 7

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.10 Test 7

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 7.

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

3.10.1 Times

Fexofenadine hydrochloride: 20 min

Pseudoephedrine hydrochloride: 45 min; 3, 5, and 12 h

Solution A: 7.0 g/L of monobasic sodium phosphate monohydrate in water. Adjust with phosphoric acid to a pH of 2.0.

Mobile phase: Acetonitrile and Solution A (45:55)

Standard stock solution A: 0.7 mg/mL of USP Fexofenadine Hydrochloride RS, prepared as follows. Transfer a quantity of USP Fexofenadine Hydrochloride RS to a suitable volumetric flask. Add methanol, NMT 5% of the flask (IRA 1-Nov-2024) volume, and sonicate to dissolve. Dilute with Medium to volume.

Standard stock solution B: 1.3 mg/mL of USP Pseudoephedrine Hydrochloride RS in Medium. Sonicate to dissolve if necessary.

Standard solution: 0.07 mg/mL of USP Fexofenadine Hydrochloride RS and 0.13 mg/mL of USP Pseudoephedrine Hydrochloride RS in Medium, from Standard stock solution A and Standard stock solution B

Sample solution: Withdraw and pass a portion of the solution under test through a suitable nylon filter of 0.45-μm pore size. Replace the portion removed with the same volume of Medium.

3.10.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 10-μm packing L6

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 1.5 times the retention time of (IRA 1-Nov-2024) pseudoephedrine (IRA 1-Nov-2024)

3.10.3 System suitability

Sample: Standard solution

3.10.4 Suitability requirements

Resolution: NLT 3.0 between fexofenadine and pseudoephedrine

Tailing factor: NMT 1.5 for fexofenadine and pseudoephedrine

Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine (IRA 1-Nov-2024)

3.10.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved:

Result = (r_U /r_S ) × C_S × V × (1/L) × 100

r_U = peak response of fexofenadine from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim for fexofenadine hydrochloride (mg/Tablet)

Calculate the concentration (C ) of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the sample withdrawn from the vessel at each time point (i)  (IRA 1-Nov-2024) :

Result_i = (r_U /r_S ) × C_S

r_U = peak response of pseudoephedrine from the Sample solution

r_S = peak response of pseudoephedrine from the Standard solution

C_S = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

[Note-Result is used as calculation correction (C₁ ) for subsequent withdrawal time points.]

Calculate the percentage of the labeled amount of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved at each time point (i) (IRA 1-Nov-2024) :

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C ₁× V_{​​​​​​​S} )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

Result₅ = {(C₅ × V) + [(C₄ + C₃ + C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

C_i = concentration of pseudoephedrine hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim for pseudoephedrine hydrochloride (mg/Tablet)

V_S = volume of the Sample solution withdrawn from the Medium (mL)

3.10.6 Tolerances

Fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl): NLT 80% (Q) of the labeled amount is dissolved in 20 min.

Pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl): See Table 8.

Table 8

^a The first time point is used as calculation correction (C ) for subsequent withdrawal time points.

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.11 Test 8

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 8.

Medium: 0.001 N hydrochloric acid; 900 mL

Apparatus 1: 10-mesh basket, 100 rpm

3.11.1 Times

Fexofenadine hydrochloride: 20 min

Pseudoephedrine hydrochloride: 3, 7, and 23 h

Buffer: 7.0 g of monobasic sodium phosphate in 1 L of water. Adjust with phosphoric acid to a pH of 2.0.

Mobile phase: Acetonitrile and Buffer (45:55)

Standard solution: 0.2 mg/mL of USP Fexofenadine Hydrochloride RS and 0.27 mg/mL of USP Pseudoephedrine Hydrochloride RS, prepared as follows. Transfer a quantity of USP Fexofenadine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS to a suitable volumetric flask, and add 0.8% of the flask volume of methanol. Add 40% of the flask volume of the Medium and sonicate to dissolve. Dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter.

3.11.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 10-μm packing L6

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 1.7 times the retention time of the pseudoephedrine peak

3.11.3 System suitability

Sample: Standard solution

3.11.4 Suitability requirements

Resolution: NLT 3.0 between fexofenadine and pseudoephedrine

Tailing factor: NMT 2.0 for fexofenadine and pseudoephedrine

Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine

3.11.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved:

Result = (r_U /r_S ) × C_S × V × (1/L) × 100

r_U = peak response of fexofenadine from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim for fexofenadine hydrochloride (mg/Tablet)

Determine the concentration (C ) of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U /r_S ) × C_S

r_U = peak response of pseudoephedrine from the Sample solution

r_S = peak response of pseudoephedrine from the Standard solution

C_S = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C ₁× V_{​​​​​​​S} )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

C_i = concentration of pseudoephedrine hydrochloride in the portion of sample withdrawn at each time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim for pseudoephedrine hydrochloride (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: For Tablets labeled to contain 180 mg of fexofenadine hydrochloride and 240 mg of pseudoephedrine hydrochloride.

Fexofenadine hydrochloride: NLT 80% (Q) of the labeled amount is dissolved in 20 min.

Pseudoephedrine hydrochloride: See Table 9.

Table 9

^a The first time point is used as calculation correction (C ) for subsequent withdrawal time points.

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

3.12 Test 9

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 9.

Medium: 0.001 N hydrochloric acid; 900 mL

3.12.1 Apparatus 2

Fexofenadine hydrochloride: 50 rpm

Pseudoephedrine hydrochloride: 50 rpm, with suitable sinkers

3.12.2 Times

Fexofenadine hydrochloride: 30 min

Pseudoephedrine hydrochloride: 30 min; 2, 4, and 12 h

Buffer: 7.0 g of monobasic sodium phosphate in 1 L of water. Adjust with phosphoric acid to a pH of 2.0.

Mobile phase: Acetonitrile and Buffer (45:55)

Standard stock solution A: 0.7 mg/mL of USP Fexofenadine Hydrochloride RS, prepared as follows. Transfer a quantity of USP Fexofenadine Hydrochloride RS to a suitable volumetric flask. Add 8% of the flask volume of methanol and sonicate to dissolve. Dilute with Medium to volume.

Standard stock solution B: 1.3 mg/mL of USP Pseudoephedrine Hydrochloride RS, prepared as follows. Transfer a quantity of USP

Pseudoephedrine Hydrochloride RS to a suitable volumetric flask. Add 8% of the flask volume of methanol and sonicate to dissolve. Dilute with Medium to volume.

Standard solution: 0.07 mg/mL of USP Fexofenadine Hydrochloride RS and 0.13 mg/mL of USP Pseudoephedrine Hydrochloride RS from Standard stock solution A and Standard stock solution B in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter.

3.12.3 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 10-μm packing L6

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 1.5 times the retention time of the pseudoephedrine peak

3.12.4 System suitability

Sample: Standard solution

3.12.5 Suitability requirements

Resolution: NLT 3.0 between fexofenadine and pseudoephedrine

Tailing factor: NMT 2.0 for fexofenadine and pseudoephedrine

Relative standard deviation: NMT 2.0% for fexofenadine and pseudoephedrine

3.12.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved:

Result = (r_U /r_S ) × C_{​​​​​​​S} × V × (1/L) × 100

r_{​​​​​​​U} = peak response of fexofenadine from the Sample solution

r_{​​​​​​​S} = peak response of fexofenadine from the Standard solution

C_{​​​​​​​S} = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim for fexofenadine hydrochloride (mg/Tablet)

Determine the concentration (C ) of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) in the sample withdrawn from the vessel at each time point (i):

Result = (r_U /r_{​​​​​​​S} ) × C_{​​​​​​​S}

r_U = peak response of pseudoephedrine from the Sample solution

r_{​​​​​​​S} = peak response of pseudoephedrine from the Standard solution

C_{​​​​​​​S} = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of pseudoephedrine hydrochloride (C₁₀H₁₅NO · HCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C ₁× V_{​​​​​​​S} )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_{​​​​​​​S} ]} × (1/L) × 100

C_i = concentration of pseudoephedrine hydrochloride in the portion of sample withdrawn at each time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim for pseudoephedrine hydrochloride (mg/Tablet)

V_{​​​​​​​S} = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: For Tablets labeled to contain 60 mg of fexofenadine hydrochloride and 120 mg of pseudoephedrine hydrochloride.

Fexofenadine hydrochloride: NLT 80% (Q) of the labeled amount is dissolved in 30 min.

Pseudoephedrine hydrochloride: See Table 10.

Table 10

The percentages of the labeled amount of pseudoephedrine hydrochloride, dissolved at the times specified, conform to Dissolution 〈711〉, Acceptance Table 2.

Uniformity of Dosage Units 〈905〉: Meet the requirements

4 IMPURITIES

[Note-On the basis of knowledge of the product, perform either: (a) Organic Impurities, Procedure 1 or (b) Organic Impurities, Procedure 2; Organic Impurities, Procedure 3; and Organic Impurities, Procedure 4.]

Change to read:

4.1 Organic Impurities, Procedure 1

Buffer, Mobile phase, (IRA 1-Nov-2024) System suitability solution, Related compounds stock solution, Related compounds solution,

Standard stock solution, Standard solution, and Chromatographic system: Proceed as directed in the Assay, Procedure 1.

Sensitivity solution: 1.2 μg/mL of USP Fexofenadine Hydrochloride RS and 2.4 μg/mL of USP Pseudoephedrine Hydrochloride RS from the Standard stock solution in Mobile phase (IRA 1-Nov-2024)

Sample solution: Nominally 1.2 mg/mL of fexofenadine hydrochloride and 2.4 mg/mL of pseudoephedrine hydrochloride from Tablets prepared as follows. Transfer whole Tablets (NLT 10) to a 500-mL volumetric flask. Add 300 mL of methanol and shake by mechanical means at high speed for 60 min. Sonicate the flask for 60 min at 40°. Add 150 mL of Buffer and sonicate for 60 min at 40°. Vent the flask, and vigorously shake the flask by hand at 15-min intervals during the mechanical shaking and sonication steps. Cool to room temperature and dilute with Buffer to volume. Pass a portion of this solution through a filter of 0.45-μm or finer pore size and use the flltrate. [Note-Alternatively, centrifuge the solution and use the supernatant.] (IRA 1-Nov-2024)

Reference solution: 0.048 mg/mL of fexofenadine hydrochloride and 0.096 mg/mL of pseudoephedrine hydrochloride from the Sample

solution in Mobile phase. Filter the solution before analysis. (IRA 1-Nov-2024)

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution (IRA 1-Nov-2024) [Note—The relative retention times in Table 11 are provided as information that could aid in peak assignment.]

Table 11 (IRA 1-Nov-2024)

^a 2-(Methylamino)-1-phenylpropan-1-one.

^b Relative to pseudoephedrine.

^c Relative to fexofenadine.

^d 2-(4-{4-[4-(Diphenylmethylene)piperidin-1-yl]-1-hydroxybutyl}phenyl)-2-methylpropanoic acid. (IRA 1-Nov-2024)

4.1.1 Suitability requirements

Resolution: NLT 1.5 (IRA 1-Nov-2024) between pseudoephedrine and methcathinone, (IRA 1-Nov-2024) System suitability solution; NLT 2.0

between fexofenadine and fexofenadine related compound A, Standard solution

Relative standard deviation: NMT 1.0% for (IRA 1-Nov-2024) pseudoephedrine  (IRA 1-Nov-2024) , System suitability solution; NMT 1.0%

for (IRA 1-Nov-2024) fexofenadine; (IRA 1-Nov-2024) and NMT 3.0% ▲each▲ (IRA 1-Nov-2024) for fexofenadine related compound A and fexofenadine related compound C, (IRA 1-Nov-2024) Standard solution Signal-to-noise ratio: NLT 10 for fexofenadine and pseudoephedrine, Sensitivity solution (IRA 1-Nov-2024)

4.1.2 Analysis

Samples: Standard solution, (IRA 1-Nov-2024) Sample solution, and Reference solution

Calculate the percentage of fexofenadine related compound A andfexofenadine related compound C (IRA 1-Nov-2024) in the portion of

Tablets taken:

Result = (r_U /r_S ) × (C_{​​​​​​​S} /C_{​​​​​​​U} ) × 100

r_{​​​​​​​U} = (IRA 1-Nov-2024) peak area response of (IRA 1-Nov-2024) fexofenadine related compound A or fexofenadine related compound C (IRA 1-Nov-2024) from the Sample solution

r_{​​​​​​​S} = peak area response of fexofenadine related compound A or fexofenadine related compound C (IRA 1-Nov-2024) from the Standard solution

C_{​​​​​​​S} = concentration of  (IRA 1-Nov-2024) USP Fexofenadine Related Compound A RS or USP Fexofenadine Related Compound C RS (IRA 1-Nov-2024) in the Standard solution (mg/mL)

C_{​​​​​​​U} = nominal concentration of fexofenadine hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of methcathinone (IRA 1-Nov-2024) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_{​​​​​​​S} /C_{​​​​​​​U} ) × (1/F) × 100

r_U = peak height response of methcathinone (IRA 1-Nov-2024) from the Sample solution

r_U = peak height response of pseudoephedrine from the Standard solution

C_U = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of pseudoephedrine hydrochloride in the Sample solution (mg/mL)

F = relative response factor for methcathinone, (IRA 1-Nov-2024) 0.394

Calculate the percentage of fexofenadine olefin or any unspecified degradation product (IRA 1-Nov-2024) in the portion of Tablets taken:

Result = r_U /(F × r_S + r_T ) × 100

r_U = (IRA 1-Nov-2024) peak area response of fexofenadine oledfin or each unspecified degradation product (IRA 1-Nov-2024) from the Sample solution

F = difference in concentration between the Sample solution and the Reference solution, 25

r_S = peak area response of fexofenadine hydrochloride from the Reference solution

r_T = sum of the peak area responses of all unspecified degradation products (IRA 1-Nov-2024) from the Sample solution (IRA 1-Nov-2024)

Acceptance criteria: See Table 12. Use an appropriate reporting threshold. See User-Determined Reporting Thresholds 〈477〉.

[Note-A reporting threshold of 0.1% may be suitable when the maximum daily dose is ≤1g.] (IRA 1-Nov-2024)

Table 12

Change to read:

4.2 Organic Impurities, Procedure 2

Solution A: Dissolve 2.7 g of monobasic potassium phosphate and 2.2 g of sodium 1-octanesulfonate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.50 ± 0.05.

Mobile phase: Methanol and Solution A (60:40) (IRA 1-Nov-2024)

Standard stock solution: 0.18 mg/mL of USP Fexofenadine Hydrochloride RS in Mobile phase

Standard solution: 0.0108 mg/mL of USP Fexofenadine Hydrochloride RS from the Standard stock solution (IRA 1-Nov-2024) in Mobile phase(IRA 1-Nov-2024)

Sensitivity solution: 1.08 (IRA 1-Nov-2024) μg/mL of USP Fexofenadine Hydrochloride RS from the Standard solution (IRA 1-Nov-2024) in Mobile phase (IRA 1-Nov-2024)

Sample solution: Nominally 1.08 mg/mL of fexofenadine hydrochloride from Tablets prepared as follows. (IRA 1-Nov-2024) Weigh and finely

powder 9 Tablets, and quantitatively transfer a suitable amount of (IRA 1-Nov-2024) the ground powder to a suitable(IRA 1-Nov-2024) volumetric flask, with the aid of 40% of the flask volume (IRA 1-Nov-2024) of Mobile phase. Sonicate for 10 min, and add an additional 20% of the flask volume (IRA 1-Nov-2024) of Mobile phase. Shake by mechanical means for 30 min, and dilute with Mobile phase to volume.

Pass a portion of the solution through a polypropylene or polysulfone membrane filter of 0.45-μm pore size, and discard an appropriatevolume (IRA 1-Nov-2024) of the filtrate.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 6 times the retention time of fexofenadine (IRA 1-Nov-2024)

4.2.2 System suitability

Samples: Standard solution and Sensitivity solution

[Note-The relative retention times in Table 13 are provided as information that could aid in peak assignment.]

Table 13 (IRA 1-Nov-2024)

^a 2-(3-{1-Hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanoic acid.

^b 2-(4-{4-[4-(Diphenylmethylene)piperidin-1-yl]-1-hydroxybutyl}phenyl)-2-methylpropanoic acid. (IRA 1-Nov-2024)

4.2.3 Suitability requirements

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the amount of each degradation product (IRA 1-Nov-2024) as a percentage of the label claim of fexofenadine hydrochloride in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_{​​​​​​​S} /C_{​​​​​​​U} ) × (1/F) × 100

r_U = peak response of each degradation product (IRA 1-Nov-2024) from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of fexofenadine hydrochloride in the Sample solution (mg/mL)

F = relative response factor for each degradation product (IRA 1-Nov-2024) (see Table 14 (IRA 1-Nov-2024) )

Acceptance criteria: See Table 14.Use an appropriate reporting threshold. See User-Determined Reporting Thresholds 〈477〉.

[Note-A reporting threshold of 0.1% may be suitable when the maximum daily dose is ≤1g.] (IRA 1-Nov-2024)

Table 14

Change to read:

4.3 Organic Impurities, Procedure 3

Solution A: 4 g/L (IRA 1-Nov-2024) of ammonium acetate

Mobile phase: Methanol and Solution A (95:5) (IRA 1-Nov-2024)

Diluent: Methanol and water (50:50) (IRA 1-Nov-2024)

Standard stock solution: 0.18 mg/mL of USP Pseudoephedrine Hydrochloride RS in Diluent

Standard solution: 0.0216 mg/mL of USP Pseudoephedrine Hydrochloride RS from the Standard stock solution in Diluent

Sensitivity solution: 2.16 (IRA 1-Nov-2024) μg/mL of USP Pseudoephedrine Hydrochloride RS from the Standard solution in Diluent

Sample solution: Nominally 2.16 mg/mL of pseudoephedrine hydrochloride from Tablets prepared as follows. (IRA 1-Nov-2024) Weigh and

nely powder 9 Tablets, and quantitatively transfer a suitable amount of (IRA 1-Nov-2024) the ground powder to a suitable (IRA 1-Nov-2024) volumetric flask, with the aid of 40% of the flask volume (IRA 1-Nov-2024) of Diluent. Sonicate for 10 min, and add an additional 20% of the flask volume (IRA 1-Nov-2024) of Diluent. Shake by mechanical means for 30 min, dilute with Diluent to volume, and mix. Pass a portion of the solution through a polypropylene or polysulfone membrane filter of 0.45-μm pore size, and discard an appropriate volume (IRA 1-Nov-2024) of the filtrate.

4.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 5-μm packing L3

Flow rate: 1 mL/min

Injection volume: 20 μL

4.3.2 System suitability

Samples: Standard solution and Sensitivity solution

[Note—The relative retention times for methcathinone and pseudoephedrine are 0.85 and 1.0, respectively. These relative retention times are provided as information that could aid in peak assignment.] (IRA 1-Nov-2024)

4.3.3 Suitability requirements

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the amount of any degradation product (IRA 1-Nov-2024) as a percentage of the label claim of pseudoephedrine hydrochloride in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_{​​​​​​​S} /C_{​​​​​​​U} ) × (1/F) × 100

r_U = peak response of each degradation product (IRA 1-Nov-2024) from the Sample solution

r_{​​​​​​​S} = peak response of pseudoephedrine from the Standard solution

C_{​​​​​​​S} = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of pseudoephedrine hydrochloride in the Sample solution (mg/mL)

F = relative response factor, (see Table 15) (IRA 1-Nov-2024)

Acceptance criteria: See Table 15. Use an appropriate reporting threshold. See User-Determined Reporting Thresholds 〈477〉.

[Note-A reporting threshold of 0.1% may be suitable when the maximum daily dose is ≤1g.]

Table 15 (IRA 1-Nov-2024)

Change to read:

4.4 Organic Impurities, Procedure 4

Solution A: Dissolve 2.7 g of monobasic potassium phosphate and 2.2 g of sodium 1-octanesulfonate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.50 ± 0.05.

Solution B: Methanol and Solution A (40:60) (IRA 1-Nov-2024)

Solution C: Methanol and Solution A (70:30) (IRA 1-Nov-2024)

Mobile phase: See Table 16.

Table 16

Diluent: Methanol and water (50:50) (IRA 1-Nov-2024)

Standard stock solution: 0.18 mg/mL of USP Benzoic Acid RS in Diluent

Standard solution: 0.0216 mg/mL of USP Benzoic Acid RS from the Standard stock solution in Diluent

Sensitivity solution: 1.08 μg/mL of USP Benzoic Acid RS from the Standard solution in Diluent

Sample solution: Nominally 2.16 mg/mL of pseudoephedrine hydrochloride from Tablets prepared as follows. (IRA 1-Nov-2024) Weigh and

nely powder 9 Tablets, and quantitatively transfer a suitable amount of (IRA 1-Nov-2024) the ground powder to a suitable (IRA 1-Nov-2024) volumetric flask, with the aid of 40% of the flask volume (IRA 1-Nov-2024) of Diluent. Sonicate for 10 min, and add an additional 20% of the flask volume (IRA 1-Nov-2024) of Diluent. Shake by mechanical means for 30 min, dilute with Diluent to volume, and mix. Pass a portion of the solution through a polypropylene or polysulfone membrane filter of 0.45-μm pore size, and discard an appropriate volume (IRA 1-Nov-2024) of the filtrate.

4.4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

4.4.2 System suitability

Samples: Standard solution and Sensitivity solution

[Note-The relative retention times in Table 17 are provided as information that could aid in peak assignment.]

Table 17 (IRA 1-Nov-2024)

^a 2-(Methylamino)-1-phenylpropan-1-one. (IRA 1-Nov-2024)

^b Methcathinone (IRA 1-Nov-2024) is not quantitated in this method. A separate method is used for the quantitation of this impurity.

4.4.3 Suitability requirements

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the amount of any degradation product (IRA 1-Nov-2024) as a percentage of the label claim of pseudoephedrine hydrochloride in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_{​​​​​​​S} /C_{​​​​​​​U} ) × (1/F) × 100

r_U = peak response of each degradation product (IRA 1-Nov-2024) from the Sample solution

r_S = peak response of benzoic acid from the Standard solution

C_S = concentration of USP Benzoic Acid RS in the Standard solution (mg/mL)

C_U = nominal concentration of pseudoephedrine hydrochloride in the Sample solution (mg/mL)

F = relative response factor for each degradation product (IRA 1-Nov-2024) (see Table 18)

Acceptance criteria: See Table 18. Use an appropriate reporting threshold. See User-Determined Reporting Thresholds 〈477〉.

[Note-A reporting threshold of 0.1% may be suitable when the maximum daily dose is ≤1g, for compounds other than benzaldehyde and benzoic acid.] (IRA 1-Nov-2024)

Table 18

^a Response factors relative to benzoic acid.

^b The response factor of pseudoephedrine relative to that of benzoic acid is used in the calculation of any (IRA 1-Nov-2024) unspecified degradation product. (IRA 1-Nov-2024)

^c Sum of the total degradation products (IRA 1-Nov-2024) from Organic Impurities, (IRA 1-Nov-2024) Procedure 3 and Procedure 4.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

Change to read:

Labeling: (IRA 1-Nov-2024) The labeling states the Dissolution (IRA 1-Nov-2024) test used only if Test 1 is not used. If a test for Organic Impurities other than Procedure 1 is used, the labeling states with which Procedures the article complies.

Change to read:

USP Reference Standards 〈11〉

USP Benzoic Acid RS

USP Fexofenadine Hydrochloride RS

USP Fexofenadine Related Compound A RS

2-(4-{4-[4-(Hydroxydiphenylmethyl)piperidin-1-yl]butanoyl}phenyl)-2-methylpropanoic acid(IRA 1-Nov-2024)

C₃₂H₃₇NO₄ 499.65

 USP Fexofenadine Related Compound C RS 4-[4-(Hydroxydiphenylmethyl)piperidin-1-yl]-1-(4-isopropylphenyl)butan-1-ol hydrochloride.

C₃₄H₃₉NO₂ · HCl 494.12 (IRA 1-Nov-2024)