Oxymorphone 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

Oxymorphone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl).

2 IDENTIFICATION

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

B. The UV absorption spectra of the oxymorphone 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 and 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 and add 250 mL of acetonitrile. Adjust with phosphoric acid to a pH of 2.1.

Mobile phase: See Table 1.

Table 1

Standard solution: 0.14 mg/mL of USP Oxymorphone RS in Solution A. Sonicate to dissolve if necessary.

Sample solution: Nominally 0.16 mg/mL of oxymorphone hydrochloride in Solution A prepared as follows. Transfer NLT 8 Tablets to a suitable volumetric flask and add about 50% of the final volume of Solution A. Sonicate for at least 15 min with occasional vigorous shaking until the Tablets disintegrate completely. Then shake for at least 20 min. Immediately dilute with Solution A to volume, and mix well. Immediately pass the solution through a suitable filter of 0.45-μm pore size, discard the first 5 mL of the filtrate, and use the filtrate for analysis.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detectors

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 Tablets 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: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Mobile phase: Dissolve 2.02 g of sodium 1-heptanesulfonate in 800 mL of water and add 200 mL of acetonitrile. Adjust with phosphoric acid to a pH of 2.1.

Standard stock solution: 0.1 mg/mL of USP Oxymorphone RS in 0.1 N hydrochloric acid

Standard solution: (L/1000) mg/mL of USP Oxymorphone RS in water from the Standard stock solution, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

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

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 60 μL

Run time: NLT 2.7 times the retention time of oxymorphone

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) dissolved:

Result = (r_U/r_S) × C_S × V × (M_r1/M_r2) × (1/L) × 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)

V = volume of Medium, 900 mL

M_r1 = molecular weight of oxymorphone hydrochloride, 337.80

M_r2 = molecular weight of oxymorphone, 301.34

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) is dissolved.

4.2 Test 2

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 20 min

Buffer: Dissolve 26.4 g of dibasic ammonium phosphate in 2 L of water.

Mobile phase: Acetonitrile, methanol, and Buffer (5:25:70)

Diluent: Buffer

Standard stock solution: 0.05 mg/mL of USP Oxymorphone RS in Medium

Standard solution: 0.0025 mg/mL of USP Oxymorphone RS in Diluent from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Dilute this solution with Diluent to obtain a solution with a similar concentration as that of the Standard solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 212 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

Run time: NLT 1.6 times the retention time of oxymorphone

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) dissolved:

Result = (r_U/r_S) × C_S × V × (M_r1/M_r2) × (1/L) × 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)

V = volume of Medium, 900 mL

M_r1 = molecular weight of oxymorphone hydrochloride, 337.80

M_r2 = molecular weight of oxymorphone, 301.34

L = label claim (mg/Tablet)

Tolerances: NLT 85% (Q) of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

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

Solution A, Solution B, Mobile phase, 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 an 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 in Solution A

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 in Solution A from System suitability stock solution C

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 Tablets taken:

Result = (r_U/r_T) × (1/F) × 100

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

r_T = sum of peak responses from the Sample solution

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

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.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at 25°, excursions permitted between 15° and 30°.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

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