Acetaminophen and Pseudoephedrine Hydrochloride 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 and Pseudoephedrine Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI).

2 IDENTIFICATION

A. The retention times of the acetaminophen and pseudoephedrine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Diluent: Acetonitrile and water (10:90)

Solution A: 0.005 M ethanesulfonic acid and 0.05 M monobasic potassium phosphate

Mobile phase: Acetonitrile and Solution A (100:900). Adjust with 5 N sodium hydroxide or 1 N hydrochloric acid to a pH of 4.6.

Pseudoephedrine hydrochloride standard stock solution: 0.6 mg/mL of USP Pseudoephedrine Hydrochloride RS in Diluent

Standard solution: Transfer 6J mg of USP Acetaminophen RS to a 100-mL volumetric flask, J being the ratio of the labeled quantity (mg) of acetaminophen to the labeled quantity (mg) of pseudoephedrine hydrochloride in each Tablet. Add 2.0 mL of 1 N hydrochloric acid and 20 mL of Diluent, and mix to dissolve. Add 10.0 mL of Pseudoephedrine hydrochloride standard stock solution and dilute with Diluent to volume.

This solution contains 0.06Jmg/mL of USP Acetaminophen RS and 0.06 mg/mL of USP Pseudoephedrine Hydrochloride RS.

Sample solution: Nominally 0.06 mg/mL of pseudoephedrine hydrochloride prepared as follows. Transfer a portion of finely powdered Tablets (NLT 20), equivalent to 30 mg of pseudoephedrine hydrochloride, to a 500-mL volumetric flask, add 10.0 mL of 1 N hydrochloric acid and 100 mL of Diluent, and sonicate for 30 min, with occasional shaking. Allow to cool, and dilute with Diluent to volume. Pass a portion of this solution through a glass fiber filter, and use the filtrate.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm x 25-cm; base-deactivated or end-capped packing 11

Flow rate: 3 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

[NOTE-The relative retention times for acetaminophen and pseudoephedrine are about 0.55 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.5 between acetaminophen and pseudoephedrine

Tailing factor: NMT 2 for the pseudoephedrine peak

Relative standard deviation: NMT 2.0% for replicate injections

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of the corresponding analyte from the Sample solution

r_S = peak response of the corresponding analyte from the Standard solution

C_S = concentration of the appropriate USP Reference Standard in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%-110.0% of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI)

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

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

Apparatus 2: 50 rpm

Time: 45 min

Determine the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI) dissolved by using the following method.

Mobile phase: Proceed as directed in the Assay.

Standard solution: (L/900) mg/mL of USP Pseudoephedrine Hydrochloride RS and (LJ/900) mg/mL of USP Acetaminophen RS in Medium.

[NOTE-L is the labeled quantity, in mg, of pseudoephedrine hydrochloride in each Tablet; and J is the ratio of the labeled quantity, in mg, of acetaminophen to the labeled quantity, in mg, of pseudoephedrine hydrochloride in each Tablet.]

Sample solution: Filtered portion of the solution under test, suitably diluted with Medium, if necessary

Chromatographic system and System suitability: Proceed as directed in the Assay, except to inject the Standard solution.

4.1.1 Analysis

Samples: Standard solution and Sample solution

[NOTE-Inject 20 µL of the Samples, and measure the responses for the acetaminophen and pseudoephedrine peaks.]

Calculate the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI) dissolved:

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

r_U = peak response of the corresponding analyte from the Sample solution

r_S = peak response of the corresponding analyte from the Standard solution

V = volume of Medium, 900 mL

C_S = concentration of the appropriate USP Reference Standard in the Standard solution (mg/mL)

L = label amount of the corresponding analyte in a Tablet (mg)

Tolerances: NLT 75% (Q) of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI) is dissolved.

4.1.2 For Tablets labeled as chewable

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

Apparatus 2: 75 rpm

Time: 45 min

Standard solution, Sample solution, Chromatographic system, System suitability, and Analysis: Proceed as directed above in Procedure for a pooled sample for immediate-release dosage forms.

Tolerances: NLT 75% (Q) of the labeled amount of acetaminophen (C₈H₉NO₂) and pseudoephedrine hydrochloride (C₁₀H₁₅NO·HCI) is dissolved.

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.

USP REFERENCE STANDARDS (11).

USP Acetaminophen RS

USP Pseudoephedrine Hydrochloride RS