Oxycodone and 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

Oxycodone and Acetaminophen Tablets contain Oxycodone hydrochloride and Acetaminophen. Tablets contain the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of oxycodone (C₁₈H₂₁NO₄), and NLT 90.0% and NMT 110.0% of the labeled amount of acetaminophen (C₈H₉NO₂).

2 IDENTIFICATION

A. Thin-Layer Chromatography

Standard solution A: 0.5 mg/mL of USP Oxycodone RS in a mixture of methanol and water (4:1)

Standard solution B: 0.5J mg/mL of USP Acetaminophen RS in a mixture of methanol and water (4:1). [Note—J is the ratio of the labeled amount, in mg, of acetaminophen to the labeled amount, in mg, of oxycodone per Tablet.]

Sample solution: Nominally equivalent to 2.5 mg of oxycodone from powdered Tablets in a 5-mL mixture of methanol and water (4:1).

Sonicate for 5 min, and shake by mechanical means for 15 min. Allow to settle, and use the clear supernatant.

2.1 Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Adsorbent: 0.25-mm layer of silica gel mixture

Application volume: 20 µL

Developing solvent system: Butyl alcohol, glacial acetic acid, and water (4:1:2)

2.2 Analysis

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

Proceed as directed in the chapter. Develop the chromatographic plate until the solvent front has moved about three-fourths of the length of the plate. Mark the solvent front, and allow the plate to air-dry for about 30 min. Expose the plate to iodine vapors in a closed chamber, and locate the spots.

Acceptance criteria: The R values of the principal spots from the Sample solution correspond to those from the respective Standard F solutions.

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

3 ASSAY

Procedure

Solution A: Methanol and 0.05 M dibasic potassium phosphate (1:9). Adjust with phosphoric acid to a pH of 4.0.

Buffer: 0.95 mg/mL of monobasic potassium phosphate in water, phosphoric acid, and n-nonylamine (1000:1:1). Prepare as follows: Add 950 mg of monobasic potassium phosphate to 1000 mL of water. Add 1 mL of phosphoric acid, and stir until dissolved. While stirring, add 1 mL of n-nonylamine, and stir until a clear solution is obtained. Adjust with potassium hydroxide TS to a pH of 4.9 ± 0.1.

Mobile phase: Methanol and Buffer (1:9)

Oxycodone standard stock solution: 0.075 mg/mL of USP Oxycodone RS in Solution A

Standard stock solution: 0.03J mg/mL of USP Acetaminophen RS and 0.03 mg/mL of USP Oxycodone RS in Solution A. Prepare by adding 40% of the ask volume of Solution A to the appropriate quantity of USP Acetaminophen RS, and then adding 40% of the ask volume of Oxycodone standard stock solution and diluting with Solution A to volume. [Note—J is the ratio of the labeled amount, in mg, of acetaminophen to that of oxycodone equivalent.]

Standard solution: 0.003J mg/mL of USP Acetaminophen RS and 0.003 mg/mL of USP Oxycodone RS in Mobile phase from Standard stock solution

Sample stock solution: Nominal equivalent of 0.03 mg/mL of oxycodone, from powdered Tablets (NLT 20), in Solution A in a suitable container. Shake by mechanical means for 1 h.

Sample solution: 0.003 mg/mL of oxycodone in Mobile phase from Sample stock solution. Pass the resulting solution through a membrane filter of 0.5-µm or finer pore size, discarding the first 10 mL of the filtrate.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 214 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Column temperature: 40° 

Flow rate: 2 mL/min 

Injection size: 20 µL 

3.2 System suitability 

Sample: Standard solution 

[Note—The relative retention times for oxycodone and acetaminophen are about 0.6 and 1.0, respectively.]

Suitability requirements 

Resolution: NLT 2.4 between acetaminophen and oxycodone 

Relative standard deviation: NMT 2.0% 

3.3 Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of oxycodone (C₁₈H₂₁NO₄ ) in the portion of Tablets taken: 

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

r_U = peak response of oxycodone from the Sample solution 

r_S = peak response of oxycodone from the Standard solution 

C_S = concentration of USP Oxycodone RS in the Standard solution (mg/mL)

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

Calculate the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 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% of the labeled amount of oxycodone (C₁₈H₂₁NO₄), and 90.0%–110.0% of the labeled amount of acetaminophen (C₈H₉NO₂)

4 PERFORMANCE TESTS

Dissolution, Procedure for a Pooled Sample〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Sample solution: Sample per Dissolution 〈711〉. Dilute with Medium as needed.

Analysis: Determine the amounts of oxycodone (C₁₈H₂₁NO₄) and acetaminophen (C₈H₉NO₂) dissolved, using the procedure in the Assay, and making any necessary volumetric adjustments, including adjusting the solution under test to a pH of about 5.5 before injecting. Tolerances: NLT 75% (Q) of the labeled amounts of oxycodone (C₁₈H₂₁NO₄) and acetaminophen (C₈H₉NO₂) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Labeling: The Tablets may be labeled to indicate the content of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) equivalent. Each mg of oxycodone is equivalent to 1.116 mg of oxycodone hydrochloride.

USP Reference Standards 〈11〉

USP Acetaminophen RS

USP Oxycodone RS