Oxycodone Hydrochloride 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 hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl). 

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. Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1- Dec-2023)

3 ASSAY

Change to read:

Procedure

Solution A: Dissolve 3.48 g of dibasic potassium phosphate in 1 L of water. Adjust with phosphoric acid to a pH of 6.7.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: 0.1% (v/v) phosphoric acid in water

Standard solution: 0.1 mg/mL of USP Oxycodone Hydrochloride RS in Diluent

Sample solution: Nominally 0.1 mg/mL of oxycodone hydrochloride in Diluent, prepared as follows. Transfer a quantity of finely powdered Tablets (NLT 20), nominally equivalent to 5 mg of oxycodone hydrochloride, to a 50-mL volumetric flask. Add 40 mL of Diluent, sonicate for about 5 min. Cool to room temperature, and agitate on a mechanical shaker for about 15 min. Dilute with Diluent to volume. Centrifuge and use the clear supernatant.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 206 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 10-cm; 3-µm packing L1

Column temperature: 45°

Flow rate: 0.7 mL/min

Injection volume: 5 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) 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 Hydrochloride RS in the Standard solution (mg/mL)

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

(USP 1-Dec-2023)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: Water; 500 mL

Apparatus 2: 50 rpm

Time: 45min

Standard solution: A known concentration of USP Oxycodone Hydrochloride RS in water (USP 1-Dec-2023) Sample solution: A portion of the solution under test. Dilute with Medium as needed.

4.1 Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: Maximum at about 225 nm

4.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) dissolved: 

Result = (A_U /A_S ) × (C_S /L) × V × D × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

D = dilution factor of the Sample solution, if applicable

(USP 1-Dec-2023)

Tolerances: NLT 70% (Q) of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

Add the following:

5 IMPURITIES

Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1.0 mg/mL of USP Oxycodone Hydrochloride RS, 0.01 mg/mL each of USP Hydrocodone RS and USP Oxycodone Related Compound A RS in Diluent

Standard solution: 2 μg/mL each of USP Oxycodone Hydrochloride RS and USP Oxycodone Related Compound B RS in Diluent Sensitivity solution: 1 μg/mL each of USP Oxycodone Hydrochloride RS and USP Oxycodone Related Compound B RS in Diluent from Standard solution

Sample solution: Nominally 1.0 mg/mL of oxycodone hydrochloride in Diluent, prepared as follows. Transfer a quantity of finely powdered Tablets (NLT 20), nominally equivalent to 20 mg of oxycodone hydrochloride, to a 20-mL volumetric flask. Add 15 mL of Diluent, and sonicate for about 5 min. Cool to room temperature, and agitate on a mechanical shaker for about 15 min. Dilute with Diluent to volume. Centrifuge and use the clear supernatant.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note—The relative retention times for hydrocodone and oxycodone related compound A are about 1.2 and 1.3, respectively.]

5.1 Suitability requirements

Resolution: NLT 1.5 between hydrocodone and oxycodone related compound A, System suitability solution

Relative standard deviation: NMT 5.0% for oxycodone and oxycodone related compound B, Standard solution

Signal-to-noise ratio: NLT 10 for oxycodone and oxycodone related compound B, Sensitivity solution

5.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxycodone related compound B in the portion of Tablets taken:

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

r_U = peak response of oxycodone related compound B from the Sample solution

r_S = peak response of oxycodone related compound B from the Standard solution

C_S = concentration of USP Oxycodone Related Compound B RS in the Standard solution (μg/mL)

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

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken:

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

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of oxycodone from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

(USP 1-Dec-2023)

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature. (USP 1-Dec-2023) Change to read:

USP Reference Standards 〈11〉

USP Hydrocodone RS

4,5α-Epoxy-3-methoxy-17-methylmorphinan-6-one.

C₁₈H₂₁NO₃            299.37

USP Oxycodone Hydrochloride RS

USP Oxycodone Related Compound A RS

4,5α-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-7-ene-6-one.

C₁₈H₁₉NO₄           313.35

USP Oxycodone Related Compound B RS

4,5α-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one N-oxide.

C₁₈H₂₁NO₅          331.37 (USP 1-Dec-2023)