Oxycodone Hydrochloride Oral Solution

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

Oxycodone hydrochloride Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ ·  HCl).

2 IDENTIFICATION

Change to read:

A. The UV spectrum of the oxycodone peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.(USP 1-May-2021)

Delete the following:

B. Thin-Layer Chromatography

Standard solution: Evaporate 5 mL of the Standard solution obtained from Identification test A just to dryness. Dissolve the residue in 1.0 mL of chloroform.

Sample solution: Evaporate 5 mL of the Sample solution obtained from Identification test A just to dryness. Dissolve the residue in 1.0 mL of chloroform.

2.1 Chromatographic system

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

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 20 µL

Developing solvent system: Acetone, toluene, ether, and ammonium hydroxide (6:4:1:0.3)

2.2 Analysis

Samples: Standard solution and Sample solution

Develop the plate until the solvent front has moved about three-fourths of the length of the plate, remove it, mark the solvent front, allow the solvent to evaporate, and spray with iodoplatinate TS.

Acceptance criteria: The principal spot from the Sample solution corresponds in color, size, and R value to that from the solution from the F

3 Standard solution, and no other spots are observed. (USP 1-May-2021)

Change to read:

B. (USP 1-May-2021) The retention time of the oxycodone peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

ASSAY

Change to read:

Procedure

Mobile phase: Acetonitrile, 0.01 M sodium 1-hexanesulfonate, and glacial acetic acid (25:74:1). Adjust with 5 N sodium hydroxide to a pH of 3.5.

Standard solution: 0.045 mg/mL of USP Oxycodone RS in Mobile phase

Sample solution: Nominally 0.05 mg/mL of oxycodone hydrochloride in Mobile phase from Oral Solution. Pass a portion of this mixture through a filter of 0.5-µm or finer pore size, and use the clear filtrate as the Sample solution.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm.For Identification A, use a diode array detector in the range of 200–400 nm. (USP 1-May-2021) Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1.7 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

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 Oral Solution taken:

Result = (r_U /r_S) × (C_S /C_U) × (M_r1 /M_r2) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

M_r1 = molecular weight of oxycodone hydrochloride, 351.82

M_r2 = molecular weight of oxycodone free base, 315.37

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Add the following:

Organic Impurities

Buffer: Dissolve 0.54 g of monobasic potassium phosphate in 1000 mL of water. Adjust with hydrochloric acid to a pH of 3.5. Add 6.5 g of anhydrous octanesulfonic acid sodium salt and readjust with hydrochloric acid to a pH of 3.5.

Solution A: Acetonitrile and Buffer (8:92)

Solution B: Acetonitrile and Buffer (45:55)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and 0.1 N hydrochloric acid (20:80)

System suitability solution: 0.45 mg/mL of USP Oxycodone RS and 0.001 mg/mL of USP Oxycodone Related Compound A RS in Diluent Sensitivity solution: 0.225 µg/mL of USP Oxycodone RS in Diluent

Standard solution: 0.0045 mg/mL of USP Oxycodone RS in Diluent

Sample solution: Nominally 0.5 mg/mL of oxycodone hydrochloride from Oral Solution in Diluent

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 10-cm; 2.6-µm packing L1

Column temperature: 45°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

4.2 System suitability

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

[Note—The relative retention times for oxycodone related compound A and 7-methyloxycodone (4,5α-Epoxy-14-hydroxy-3-methoxy-7,17- dimethylmorphinan-6-one) are 1.05 and 1.17, respectively.]

Suitability requirements

Resolution: NLT 2.0 between oxycodone and oxycodone related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual degradation product in the portion of Oral Solution taken:

Result = (r_U /r_S) × (C_S /C_U) × (M_r1 /M_r2) × (1/F) × 100

U S S U r1 r2

r_U = peak response of each individual degradation product from the Sample solution

r_S = peak response of oxycodone from the Standard solution

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

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

M_r1 = molecular weight of oxycodone hydrochloride, 351.82

M_r2 = molecular weight of oxycodone free base, 315.37

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

(USP 1-May-2021)

5 OTHER COMPONENTS

Alcohol Determination 〈611〉, Procedures, Method II (if present): 85.0%–115.0% of the labeled amount of alcohol (C H OH), determined by the 2 5

gas–liquid chromatographic method, using acetone as the internal standard

6 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉

For Oral Solution packaged in single-unit containers: Meets the requirements

Deliverable Volume 〈698〉

For Oral Solution packaged in multiple-unit containers: Meets the requirements

7 SPECIFIC TESTS

pH 〈791〉: 1.4–4.6

ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature. (USP 1-May-2021)

Change to read:

USP Reference Standards 〈11〉

USP Oxycodone RS

USP Oxycodone Related Compound A RS

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

C₁₈H₁₉NO₄         313.35    (USP 1-May-2021)