Acetaminophen, Chlorpheniramine Maleate, and Dextromethorphan Hydrobromide 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

Acetaminophen, Chlorpheniramine Maleate, and Dextromethorphan Hydrobromide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of Acetaminophen (C₈H₉NO₂), chlorpheniramine maleate (C₁₆H₁₉CIN₂·C₄H₄O₄), and dextromethorphan hydrobromide monohydrate (C₁₈H₂₅NO·HBr·H₂O).

2 IDENTIFICATION

A. The retention time of the major peak for acetaminophen of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Acetaminophen.

B. The retention time of the major peak for chlorpheniramine of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Chlorpheniramine Maleate.

C. The retention time of the major peak for dextromethorphan of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Dextromethorphan Hydrobromide.

3 ASSAY

3.1 ACETAMINOPHEN

Mobile phase: Methanol, glacial acetic acid, and water (20:1:79)

Standard solution: 0.5 mg/mL of USP Acetaminophen RS prepared as follows. Transfer an appropriate amount of USP Acetaminophen RS to a suitable volumetric flask and add methanol using 4% of the final volume. Mix until solution is complete and dilute with 0.1% phosphoric acid to volume.

Sample stock solution: Nominally 2 mg/mL of acetaminophen prepared as follows. Transfer a portion of powdered Tablets (NLT 20), equivalent to 100 mg of acetaminophen, to a 50-mL volumetric flask. Add 7.5 mL of methanol, and sonicate to disperse the powder. Add 0.5 mL of phosphoric acid, dilute with water to volume, and filter.

Sample solution: Nominally 0.5 mg/mL of acetaminophen from Sample stock solution in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm x 15-cm; 5-µm packing L7

Flow rate: 1 mL/min

Injection volume: 10 µL

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 the labeled amount of acetaminophen (C₈H₉NO₂) in the portion of Tablets taken:

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

r_U = peak response of acetaminophen from the Sample solution

r_S = peak response of acetaminophen from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0% of the labeled amount of acetaminophen (C₈H₉NO₂)

3.2 CHLORPHENIRAMINE MALEATE

Mobile phase: Methanol and water (60:40) containing 0.34 g of monobasic potassium phosphate, 0.3 g of triethylamine hydrochloride, 0.15 g of sodium lauryl sulfate, and 0.1 mL of phosphoric acid in each 100 mL of solution

Standard stock solution: 0.8 mg/mL of USP Chlorpheniramine Maleate RS in water

Standard solution: 8 µg/mL of USP Chlorpheniramine Maleate RS in 0.1% phosphoric acid from Standard stock solution

Sample solution: Nominally 8 µg/mL of chlorpheniramine maleate prepared as follows. Transfer a portion of powdered Tablets (NLT 20), equivalent to 2 mg of chlorpheniramine maleate, to a 250-mL volumetric flask. Add 25 mL of methanol, and sonicate to disperse the powder. Add 1 mL of phosphoric acid, dilute with water to volume, and filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 15-cm; 5-µm packing L11

Flow rate: 2 mL/min

Injection volume: 10 µL

System suitability

Samples: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of chlorpheniramine maleate (C₁₆H₁₉CIN₂·C₄H₄O₄) in the portion of Tablets taken:

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

r_U = peak response of chlorpheniramine from the Sample solution

r_S = peak response of chlorpheniramine from the Standard solution

C_S = concentration of USP Chlorpheniramine Maleate RS in the Standard solution (mg/mL)

C_U = nominal concentration of chlorpheniramine maleate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0% of the labeled amount of chlorpheniramine maleate (C₁₆H₁₉CIN₂·C₄H₄O₄)

3.3 DEXTROMETHORPHAN HYDROBROMIDE

Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay for Chlorpheniramine Maleate.

Standard stock solution: 0.6 mg/mL of USP Dextromethorphan Hydrobromide RS in water

Standard solution: 0.06 mg/mL of USP Dextromethorphan Hydrobromide RS in 0.1% phosphoric acid, from Standard stock solution

Sample solution: Nominally 0.06 mg/mL of dextromethorphan hydrobromide prepared as follows. Transfer a portion of powdered Tablets (NLT 20), equivalent to 6 mg of dextromethorphan hydrobromide, to a 100-mL volumetric flask. Add 10 mL of methanol, and sonicate to disperse the powder. Add 0.4 mL of phosphoric acid, dilute with water to volume, and filter.

System suitability

Samples: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of dextromethorphan hydrobromide monohydrate (C₁₈H₂₅NO·HBr·H₂O) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of dextromethorphan from the Sample solution

r_S = peak response of dextromethorphan from the Standard solution

C_S = concentration of USP Dextromethorphan Hydrobromide RS in the Standard solution (mg/mL)

C_U = nominal concentration of dextromethorphan hydrobromide in the Sample solution (mg/mL)

M_r1 = molecular weight of dextromethorphan hydrobromide monohydrate, 370.32

M_r2 = molecular weight of anhydrous dextromethorphan hydrobromide, 352.32

Acceptance criteria: 90.0%-110.0% of the labeled amount of dextromethorphan hydrobromide monohydrate (C₁₈H₂₅NO·HBr·H₂O)

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711), Procedure, Apparatus 1 and Apparatus 2, Immediate-Release Dosage Forms, Procedure for a pooled sample for immediate-release dosage forms

4.1.1 Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Sample solution: Mix 9.0 mL of a filtered portion of the solution with 1.0 mL of 1% phosphoric acid solution.

Analysis: Determine the percentage of the labeled amount of acetaminophen, chlorpheniramine maleate, and dextromethorphan hydrobromide dissolved, using the Analysis set forth in the Assay for Acetaminophen, the Assay for Chlorpheniramine Maleate, and the Assay for Dextromethorphan Hydrobromide, respectively, making any necessary volumetric adjustments.

Tolerances: NLT 75% (Q) of the labeled amount of acetaminophen (C₈H₉NO₂), chlorpheniramine maleate (C₁₆H₁₉CIN₂·C₄H₄O₄), and dextromethorphan hydrobromide monohydrate (C₁₈H₂₅NO·HBr·H₂O) is dissolved.

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

Medium: 0.1 M hydrochloric acid: 900 mL

Apparatus 2, Time, Sample solution, Analysis, and Tolerances: Proceed as directed in Test 1.

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

Medium: pH 5.8 phosphate buffer (see Reagents, Indicators, and Solutions-Buffer Solutions); 900 mL

Apparatus 2, Time, Sample solution, Analysis, and Tolerances: Proceed as directed in Test 1.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG PRODUCTS (227): Meet the requirements

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

LABELING: The label states the name and quantity of each active ingredient and indicates its function (or purpose) in the article. When more 1 is not used. than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1

USP REFERENCE STANDARDS (11).

USP Acetaminophen RS

USP Chlorpheniramine Maleate RS

USP Dextromethorphan Hydrobromide RS