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

2 IDENTIFICATION

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

B. The UV spectrum of the acetaminophen peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: 1% (v/v) glacial acetic acid in water

Solution B: Methanol

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system for 4 min.

Table 1

Diluent: Methanol and water (10:90)

Standard solution: 0.01 mg/mL of USP Acetaminophen RS in Diluent

Sample stock solution: Nominally 0.1 mg/mL of acetaminophen in Diluent prepared as follows. Transfer an appropriate amount of acetaminophen from NLT 10 Tablets to a suitable volumetric flask and dilute with Diluent to volume. Centrifuge or pass a portion of this solution through a suitable filter. [NOTE-Sonication or shaking may be necessary.]

Sample solution: Nominally 0.01 mg/mL of acetaminophen in Diluent from the Sample stock solution. Pass a portion of this solution through a suitable filter.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 243 nm. For Identification B, use a diode array detector in the range of 220-400 nm.

Column: 3.0-mm x 10-cm; 3.5-µm packing 11

Column temperature: 40°

Flow rate: 0.5 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.4 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%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

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

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: A known concentration of USP Acetaminophen RS in Medium

Sample solution: A filtered portion of the solution under test, suitably diluted with Medium to obtain a concentration similar to that of the Standard solution

4.1.1 Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 243 nm

4.1.2 Analysis

Samples: Standard solution and Sample solution

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

Tolerances: NLT 80% (Q) of the labeled amount of acetaminophen (C₈H₉NO₂) is dissolved.

4.1.3 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, Instrumental conditions, and Analysis: Proceed as directed above.

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

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

5.1 ORGANIC IMPURITIES

It is suggested to protect all solutions containing acetaminophen or 4-aminophenol from light.

Buffer: Dissolve 1.9 g of ammonium formate in 1 L of water. Add 1.0 mL of formic acid.

Solution A: Dissolve 3.1 g of ammonium acetate in 1 L of water. Add 1.0 mL of trifluoroacetic acid.

Solution B: Acetonitrile, methanol, and water (10:75:15)

Solution C: Dissolve 3.1 g of ammonium acetate in 1000 mL of Solution B. Add 1.0 mL of trifluoroacetic acid.

Mobile phase: See Table 2. Return to original conditions and re-equilibrate the system for 4 min.

Table 2

Diluent: Methanol and Buffer (5:95)

Sensitivity solution: 0.000175 mg/mL of USP 4-Aminophenol RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution: 0.00175 mg/mL of USP 4-Aminophenol RS and 0.0035 mg/mL of USP Acetaminophen RS in Diluent. Sonicate to dissolve, if necessary.

Sample stock solution: Nominally 5 mg/mL of acetaminophen in Diluent from NLT 10 Tablets. [NOTE-It is recommended to shake on a flat bed at low speed (180 oscillations/min) to dissolve, if necessary.]

Sample solution: Nominally 3.5 mg/mL of acetaminophen in Diluent prepared as follows. Pass a portion of the Sample stock solution through a suitable filter of 0.2-um pore size. Discard the first 2 mL of the filtrate. Dilute a suitable volume of the filtrate with Diluent to volume.

5.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 272 nm (ERR 1-Oct-2021)

Column: 4.6-mm x 15-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 0.9 mL/min

Injection volume: 25 µL

5.3 System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0% for 4-aminophenol and acetaminophen, Standard solution

Signal-to-noise ratio: NLT 10 for 4-aminophenol, Sensitivity solution

5.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 4-aminophenol in the portion of Tablets taken:

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

r_U = peak response of 4-aminophenol from the Sample solution

r_S = peak response of 4-aminophenol from the Standard solution

C_S = concentration of USP 4-Aminophenol RS in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Tablets taken:

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

r_U = peak response of any unspecified impurity 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: See Table 3.

Table 3

6 ADDITIONAL REQUIREMENTS

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

LABELING: Label Tablets that must be chewed to indicate that they are to be chewed before swallowing.

USP REFERENCE STANDARDS (11)

USP Acetaminophen RS

USP 4-Aminophenol RS

4-Aminophenol.

C₆H₇NO 109.13