Acetaminophen and Aspirin 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 Aspirin Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of acetaminophen (C₈H₉NO₂) and aspirin (C₉H₈O₄).

2 IDENTIFICATION

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

3 ASSAY

3.1 PROCEDURE

[NOTE-Use clean and dry glassware. Inject the Standard solution and the Sample solution promptly after preparation.]

Solution A: Chloroform, methanol, and glacial acetic acid (78:20:2)

Mobile phase: Transfer 225 mg of tetramethylammonium hydroxide pentahydrate to a 1000-mL flask. Add 750 mL of water, 125 mL of methanol, 125 mL of acetonitrile, and 1.0 mL of glacial acetic acid, Stir for 3 min, and pass through a membrane filter of 0.5-µm or finer pore size.

Internal standard solution: 20 mg/mL of benzoic acid in Solution A

Standard solution: 3.25 mg/mL each of USP Acetaminophen RS and USP Aspirin RS, and 2.0 mg/mL of benzoic acid, from Internal standard solution, in Solution A

Sample solution: Nominally 3.25 mg/mL of acetaminophen in Solution A, prepared as follows. Transfer an equivalent of 325 mg of acetaminophen, from NLT 20 finely powdered Tablets, to a 100-mL volumetric flask. Add 10.0 mL of Internal standard solution and 50 mL of Solution A, and sonicate for 3 min. Dilute with Solution A to volume. Pass a portion of this solution through a filter of 2.5-µm or finer pore size. Use the filtrate.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.9-mm x 30-cm; packing 11

Flow rate: 2 mL/min

Injection volume: 5 µL

3.3 System suitability

Sample: Standard solution

[NOTE-The retention times for acetaminophen, salicylic acid (if present), aspirin, and benzoic acid are about 2, 3, 5, and 8 min, respectively.]

Suitability requirements

Relative standard deviation: NMT 3.0% for acetaminophen or aspirin for four replicate injections

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate individually the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) and aspirin (C₉H₈O₄) in the portion of Tablets taken:

Result = (R_U/R_S) x (C_S/C_U) × 100

R_U = peak response ratio of acetaminophen or aspirin to benzoic acid from the Sample solution

R_S = peak response ratio of acetaminophen or aspirin to benzoic acid from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0% of the labeled amount of acetaminophen (C₈H₉NO₂) and aspirin (C₉H₈O₄)

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

4.1.1 Procedure for a pooled sample

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Solution A, Mobile phase, and Chromatographic system (except for Injection volume): Proceed as directed in the Assay.

Injection volume: 20 µL

Internal standard solution: 1 mg/mL of benzoic acid in methanol

Standard stock solution A: 70 µg/mL of USP Salicylic Acid RS in Solution A

Standard solution A: Combine 4.0 mL of Standard stock solution A and 1.0 mL of Internal standard solution.

Standard stock solution Β: 360 µg/mL each of USP Acetaminophen RS and USP Aspirin RS in Solution A

Standard solution B: Combine 4.0 mL of Standard stock solution B and 1.0 mL of Internal standard solution.

Sample stock solution: Filtered portions of sample suitably diluted with Medium to a concentration that is similar to that of Standard stock

solution A or Standard stock solution B

Sample solution: Combine 4.0 mL of the Sample stock solution and 1.0 mL of Internal standard solution.

4.1.2 Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

[NOTE-The relative retention times for acetaminophen, salicylic acid, aspirin, and benzoic acid are about 0.3, 0.4, 0.6, and 1.0, respectively.]

Calculate the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) dissolved:

Result = (R_U/R_S) x (C/W) x 90

R_U = relative peak response ratio of acetaminophen to the internal standard from the Sample solution

R_S = relative peak response ratio of acetaminophen to the internal standard from Standard solution B

C= concentration of USP Acetaminophen RS in Standard solution B (µg/mL)

W = labeled amount of acetaminophen (mg)

Calculate the percentage of the labeled amount of aspirin (C₉H₈O₄) dissolved:

Result = {[90C₁ × (R_U1/R_S1)] + [90C₂× (R_U2/R_S2) x 1.3044]}/W

C₁ = concentration of USP Aspirin RS in Standard solution B (µg/mL)

R_U1 = relative peak response ratio of aspirin to the internal standard from the Sample solution

R_S1 = relative peak response ratio of aspirin to the internal standard from Standard solution B

C₂ = concentration of USP Salicylic Acid RS in Standard solution A (µg/mL) C₂

R_U2 = relative peak response ratio of salicylic acid to the internal standard from the Sample solution

R_S2 = relative peak response ratio of salicylic acid to the internal standard from Standard solution A

W = labeled amount of aspirin (mg)

Tolerances: NLT 75% (Q) of the labeled amount of acetaminophen (C₈H₉NO₂) and aspirin (C₉H₈O₄) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905), Content Uniformity

Meet the requirements with respect to acetaminophen and to aspirin

5 IMPURITIES

5.1 LIMIT OF SALICYLIC ACID

Solution A, Mobile phase, Internal standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard stock solution: 1.0 mg/mL of USP Salicylic Acid RS in Solution A

Standard solutions: Transfer 1.0-, 5.0-, and 10.0-mL portions of Standard stock solution to separate 100-mL volumetric flasks. Add 10.0 mL of

Internal standard solution to each flask, and dilute with Solution A to volume.

5.2 Analysis

Samples: Sample solution and Standard solutions

Plot the ratios of the peak responses for salicylic acid and benzoic acid for each of the Standard solutions versus concentrations, in mg/mL, of salicylic acid, and draw the straight line best fitting the three plotted points. From the graph so obtained, and from the ratio of the peak responses for salicylic acid and benzoic acid from the Sample solution as obtained in the Assay, determine the concentration, in mg/mL, of salicylic acid (C₇H₆O₃) in the Sample solution.

Calculate the percentage of salicylic acid in relation to the concentration of aspirin in the Sample solution, as obtained in the Assay.

Acceptance criteria: NMT 3.0%

5.3 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 Aspirin RS

USP Salicylic Acid RS