Acetaminophen Suppositories

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

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

2 IDENTIFICATION

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

B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Sample solution: Transfer the equivalent of 20 mg of acetaminophen from a portion of Suppositories to a beaker. Add 20 mL of methanol and heat on a steam bath until melted. Remove the beaker from the steam bath, allow to cool with occasional stirring, and filter. Use the clear filtrate.

Chromatographic system

Developing solvent system: Methylene chloride and methanol (4:1)

Acceptance criteria: Meet the requirements

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol and water (1:3)

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

Sample stock solution: Nominally 0.5 mg/mL of acetaminophen prepared as follows. Tare a small dish and a glass rod, place NLT 5 Suppositories in the dish, heat gently on a steam bath until melted, stir, cool while stirring, and weigh. Transfer a weighed portion of the mass, equivalent to 100 mg of acetaminophen, to a separator, add 30 mL of solvent hexane, and dissolve. Add 30 mL of water, shake gently, and allow the phases to separate. If an emulsion forms, allow sufficient time for it to separate. Transfer the aqueous layer to a 200-mL volumetric flask, and wash the solvent hexane in the separator with three 30-mL portions of water, adding the washings to the volumetric flask. Dilute with Mobile phase to volume.

Sample solution: Nominally 0.01 mg/mL of acetaminophen in Mobile phase from the Sample stock solution. Pass a portion of this solution through a filter of 0.5-µm or finer pore size, discarding the first 10 mL of the filtrate. Use the clear filtrate.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 243 nm

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

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 Suppositories taken:

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

r_U = peak response from the Sample solution

r_S = peak response 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 IMPURITIES

4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG PRODUCTS (227).

Buffer: 4.0 g/L of sodium citrate dihydrate and 1.5 g/L of anhydrous citric acid, in water

Diluent: Buffer and acetonitrile (9:1)

Sample stock solution: Approximately 12-13 mg/mL of acetaminophen prepared as follows. Transfer an appropriate number of whole Suppositories to a suitable volumetric flask. Add Diluent until the flask is about half filled and sonicate for 1 h with frequent swirling. Allow to cool and then dilute with Diluent to volume.

Sample solution: Approximately 4.8-5.2 mg/mL of acetaminophen in Diluent from the Sample stock solution prepared as follows. Pipet 20.0 mL of the Sample stock solution into a 50-mL volumetric flask and dilute with Diluent to volume.

Standard stock solution: Prepare as indicated in the chapter.

Standard solution: Add 20.0 mL of the Sample stock solution and 15.0 mL of the Standard stock solution to a 50-mL volumetric flask, and dilute with Diluent to volume.

Acceptance criteria: Meet the requirements

5 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11).

USP Acetaminophen RS