Acetaminophen and Caffeine 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 Caffeine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amounts of acetaminophen (C₈H₉NO₂) and caffeine (C₈H₁₀N₄O₂).

2 IDENTIFICATION

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

3 ASSAY

3.1 PROCEDURE

Solution A: Methanol and glacial acetic acid (95:5)

Mobile phase: Methanol, glacial acetic acid, and water (28:3:69)

Internal standard solution: 6 mg/mL of benzoic acid in methanol

Standard stock solution: 0.25 mg/mL of USP Acetaminophen RS and 0.25 mg/mL of USP Caffeine RS in Solution A; J being the ratio of the labeled amount, in mg, of caffeine to the labeled amount, in mg, of acetaminophen per Tablet

Standard solution: 0.1 mg/mL of USP Acetaminophen RS and 0.1J mg/mL of USP Caffeine RS, prepared by transferring 20.0 mL of Standard stock solution and 3.0 mL of Internal standard solution to a 50-mL volumetric flask, and diluting with Solution A to volume

Sample stock solution: Nominally 2.5 mg/mL of acetaminophen in Solution A, prepared as follows. Transfer a portion of the powder equivalent to 250 mg of acetaminophen, from NLT 20 finely powdered Tablets, to a 100-mL volumetric flask. Add 75 mL of Solution A, and shake by mechanical means for 30 min. Dilute with Solution A to volume.

Sample solution: Transfer 2.0 mL of the Sample stock solution and 3.0 mL of Internal standard solution to a 50-mL volumetric flask, and dilute with Solution A to volume.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 275 nm

OFFICI

Column: 4.6-mm × 10-cm; 5-µm packing L1

Column temperature: 45 ± 1°

Flow rate: 2 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

[NOTE-The relative retention times for acetaminophen, caffeine, and benzoic acid are about 0.3, 0.5, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.4 between any of the analyte and internal standard peaks

Tailing factor: NMT 1.2 for each analyte peak

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate individually the percentages of the labeled amounts of acetaminophen (C₈H₉NO₂) and caffeine (C₈H₁₀N₄O₂) 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 caffeine to the internal standard from the Sample solution

R_S = peak response ratio of acetaminophen or caffeine to the internal standard from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0% of acetaminophen (C₈H₉NO₂) and caffeine (C₈H₁₀N₄O₂)

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: Water; 900 mL

Apparatus 2: 100 rpm

Time: 60 min

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

Standard solution: Transfer 20.0 mL of the Standard stock solution, 3.0 mL of Internal standard solution, and 20 mL of water to a 50-mL volumetric flask, and allow to stand for 30 s. Dilute with Solution A to volume. Use within 8 h.

Sample solution: Transfer an aliquot of a filtered portion of the solution under test to a 50-mL volumetric flask to obtain an expected concentration of 0.1 mg/mL of acetaminophen and 0.1J mg/mL of caffeine, where J is defined for the Standard stock solution. Add 3.0 mL of Internal standard solution and 20 mL of Solution A, and allow to stand for 30 s. Dilute with Solution A to volume.

Analysis: Proceed as directed in the Assay, using the Standard solution and Sample solution prepared within the Dissolution test. Calculate the percentages of the labeled amounts of acetaminophen (C₈H₉NO₂) and caffeine (C₈H₁₀N₄O₂) dissolved:

Result = (R_U/R_S) x (C_S/C_U) × 100

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

R_S = peak response ratio of acetaminophen or caffeine to the internal standard from the Standard solution

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

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

Tolerances: NLT 75% (Q) of the labeled amounts of acetaminophen (C₈H₉NO₂) and caffeine (C₈H₁₀N₄O₂) 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 Caffeine RS