Oxymorphone Hydrochloride Injection

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

Oxymorphone Hydrochloride Injection is a sterile solution of Oxymorphone Hydrochloride in Water for Injection. It contains NLT 93.0% and NMT 107.0% of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · 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.

B. The UV absorption spectra of the major peak of the Sample solution and that of the Standard solution exhibit maxima and minima at the same wavelengths, as obtained in the Assay.

3 ASSAY

Procedure

Protect all solutions containing oxymorphone from light and use clear glass HPLC vials.

Solution A: Dissolve 2.02 g of sodium 1-heptanesulfonate in 900 mL of water. Add 100 mL of acetonitrile. Adjust with phosphoric acid to a pH of 2.1.

Solution B: Dissolve 2.02 g of sodium 1-heptanesulfonate in 750 mL of water. Add 250 mL of acetonitrile. Adjust with phosphoric acid to a pH of 2.1.

Mobile phase: See Table 1.

Table 1

Diluent: Dissolve 2.02 g of anhydrous sodium 1-heptanesulfonate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.1.

Standard solution: 0.14 mg/mL of USP Oxymorphone RS prepared as follows. Transfer a suitable amount of USP Oxymorphone RS to a suitable volumetric flask. Add 50% of the flask volume of Diluent. Sonicate to dissolve, if necessary. Add 9% of the flask volume of acetonitrile. Cool to room temperature and dilute with Diluent to volume.

Sample solution: Nominally 0.15 mg/mL of oxymorphone hydrochloride from Injection prepared as follows. Transfer a suitable volume of the composite sample from NLT 20 ampules to a suitable volumetric flask. Dilute with Solution A to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector

Assay: UV 230 nm

Identification test B: Diode array UV 200–360 nm

Column: 4.6-mm × 7.5-cm; 3.5-μm packing L1

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 30 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) in the portion of Injection taken:

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

r_U = peak response of oxymorphone from the Sample solution

r_S = peak response of oxymorphone from the Standard solution

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

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

M_r1 = molecular weight of oxymorphone hydrochloride, 337.80

M_r2 = molecular weight of oxymorphone, 301.34

Acceptance criteria: 93.0%–107.0%

4 IMPURITIES

Organic Impurities

Protect all solutions containing oxymorphone from light and use clear glass HPLC vials.

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

System suitability stock solution A: 0.2 mg/mL of USP Oxymorphone Related Compound A RS prepared as follows. Transfer a suitable amount of USP Oxymorphone Related Compound A RS to a suitable volumetric flask. Dissolve with 24% of the flask volume of 0.1 N hydrochloric acid and dilute with acetonitrile to volume.

System suitability stock solution B: 0.02 mg/mL of USP Oxymorphone Related Compound A RS in acetonitrile from System suitability stock solution A

System suitability stock solution C: 0.14 mg/mL of USP Oxymorphone RS prepared as follows. Transfer a suitable amount of USP Oxymorphone RS to a suitable volumetric flask. Add 50% of the flask volume of Diluent. Sonicate to dissolve if necessary. Add 9% of the flask volume of acetonitrile. Cool to room temperature and dilute with Diluent to volume.

System suitability solution: 0.0008 mg/mL of USP Oxymorphone Related Compound A RS in System suitability stock solution C from System suitability stock solution B

Standard solution: 0.00014 mg/mL of USP Oxymorphone RS prepared as follows. Dilute System suitability stock solution C with Solution A.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2 between oxymorphone related compound A and oxymorphone, System suitability solution

Relative standard deviation: NMT 10%, Standard solution

Analysis

Sample: Sample solution

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

Result = {(r_U/F)/[r_S + Σ(r_U/F)]} × 100

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

F = relative response factor of each individual degradation product (see Table 2)

r_S = peak response of oxymorphone from the Sample solution

Acceptance criteria: See Table 2. Disregard any peaks less than 0.05%.

Table 2

^a 4,5α-Epoxy-3,10,14-trihydroxy-17-methylmorphinan-6-one.

^b 4,5α-Epoxy-3,14-dihydroxy-17-methylmorphinan-6,10-dione.

^c Process impurities, not included in the total degradation products.

^d 1-Bromo-4,5α-epoxy-3,14-dihydroxy-17-methylmorphinan-6-one.

^e 2,2'-Bioxymorphone.

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 238.1 USP Endotoxin Units/mg of oxymorphone hydrochloride

pH 〈791〉: 2.7–4.5

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or in multiple-dose containers of Type I glass. Store at 25°, excursions permitted between 15° and 30°, and protected from light.

USP Reference Standards 〈11〉

USP Oxymorphone RS

USP Oxymorphone Related Compound A RS

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

C₁₇H₁₉NO₅ 317.34