Oxymorphone Hydrochloride Extended-Release 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 Extended-Release 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 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

Solution A: Dissolve 2.34 g of sodium 1-octanesulfonate monohydrate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.80.

Solution B: Acetonitrile and methanol (50:50)

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and phosphoric acid (1000:1)

Standard stock solution: 1.78 mg/mL of USP Oxymorphone RS in Diluent

Standard solution: 0.357 mg/mL of USP Oxymorphone RS in Solution A from the Standard stock solution

Sample stock solution: Nominally 2 mg/mL of oxymorphone hydrochloride in Diluent prepared as follows. Take NLT 8 Tablets, cut each into small pieces, and transfer to a suitable flask. Add a suitable volume of Diluent and shake for at least 16 h. Centrifuge at 3500 rpm for 5 min or until a clear supernatant is obtained.

Sample solution: Nominally 0.4 mg/mL of oxymorphone hydrochloride in Solution A from the Sample stock solution

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: 50°

Flow rate: 1.0 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8 - 1.5

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: 45 mM phosphate buffer, pH 4.50 (dissolve 6.16 g of monobasic potassium phosphate in 1 L of water. Adjust with 1 N sodium hydroxide or phosphoric acid to a pH of 4.50); 900 mL

Apparatus 2: 50 rpm, with sinker. [Note—The Sotax Helix sinker can be used.]

Times: 1, 2, and 8 h

Mobile phase: Dissolve 1.54 g of ammonium acetate in 925 mL of water and mix well. Add 75 mL of acetonitrile and adjust with trifluoroacetic acid to a pH of 4.50.

Standard stock solution: 0.2 mg/mL of USP Oxymorphone RS in Medium

Standard solution: [(L/900) × (301.34/337.80)] mg/mL of USP Oxymorphone RS in Medium from the Standard stock solution, where L is the label claim in mg/Tablet

Sample solution: Withdraw 1.5 mL of the solution under test.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 7.5-cm; 4-μm packing L11

Column temperature: 60°

Flow rate: 2.0 mL/min

Injection volume: 50 μL

Run time: NLT 2 times the retention time of oxymorphone

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8–1.5

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 at each time point (i):

Result_i = (r_U/r_S) × C_S × (M_r1/M_r2) × V × (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)

M_r1 = molecular weight of oxymorphone hydrochloride, 337.80

M_r2 = molecular weight of oxymorphone, 301.34

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: See Table 2.

Table 2

The percentages of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) dissolved at the times specified conform to

Dissolution 〈711〉, Acceptance Table 2.

4.2 Test 2

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

Apparatus 2, Mobile phase, Standard stock solution, Standard solution, Sample solution, Chromatographic system, System suitability, and Analysis: Proceed as directed in Test 1.

Medium: 50 mM phosphate buffer, pH 4.50 (dissolve 6.8 g of monobasic potassium phosphate in 1 L of water. Adjust with 1 N sodium hydroxide or phosphoric acid to a pH of 4.50); 900 mL

Times: 1, 4, and 10 h

Tolerances: See Table 3.

Table 3

The percentages of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) dissolved at the times specified conform to

Dissolution 〈711〉, Acceptance Table 2.

4.3 Test 3

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.

Medium: 50 mM phosphate buffer, pH 4.50 (dissolve 40.8 g of monobasic potassium phosphate in 6 L of water. Adjust with 1 N potassium hydroxide or phosphoric acid to a pH of 4.50); 900 mL

Apparatus 2: 50 rpm

Times: 1, 4, and 14 h

Buffer: 0.1 M ammonium phosphate prepared as follows. Dissolve 13.2 g of dibasic ammonium phosphate in 1 L of water, and mix well.

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

Standard solution: 0.0112 mg/mL of USP Oxymorphone RS in Medium

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 212 nm

Column: 4.6-mm × 15.0-cm; 5-μm packing L7

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

Run time: NLT 2 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 concentration (C_i) of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U/r_S) × C_S × (M_r1/M_r2)

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)

M_r1 = molecular weight of oxymorphone hydrochloride, 337.80

M_r2 = molecular weight of oxymorphone, 301.34

Calculate the percentage of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) dissolved at each time point (i):

Result₁ = C₁ × V_S × (1/L) × 100

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S)]} + [(C₂ + C₁) × V_S]) × (1/L) × 100

C_i = concentration of oxymorphone hydrochloride in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (i) (mL)

Tolerances: See Table 4.

Table 4

The percentages of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.

4.4 Test 4

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 4.

Medium: 50 mM phosphate buffer, pH 6.8 (dissolve 6.8 g of monobasic potassium phosphate in 250 mL of water, and add 77 mL of 0.2 N sodium hydroxide and 500 mL of water. Adjust with 0.2 N sodium hydroxide or 0.2 N hydrochloric acid to a pH of 6.8 and dilute with water to 1 L); 900 mL

Apparatus 2: 50 rpm

Times: 1, 4, and 10 h

Buffer: Triethylamine and water (2:1000). Adjust with phosphoric acid or 5 N sodium hydroxide to a pH of 6.8.

Mobile phase: Acetonitrile and Buffer (14:86)

Standard solution: [(L/900) × (301.34/337.80)] mg/mL of USP Oxymorphone RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 15.0-cm; 5-μm packing L11

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 10 μL for 10-, 15-, 20-, 30-, and 40-mg strengths; 20 μL for 5- and 7.5-mg strengths

Run time: NLT 1.5 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 concentration (C_i) of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U/r_S) × C_S × (M_r1/M_r2)

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)

M_r1 = molecular weight of oxymorphone hydrochloride, 337.80

M_r2 = molecular weight of oxymorphone, 301.34

Calculate the percentage of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S)]} + [(C₂ + C₁) × V_S]) × (1/L) × 100

C_i = concentration of oxymorphone hydrochloride in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (i) (mL)

Tolerances: See Table 5.

Table 5

The percentages of the labeled amount of oxymorphone hydrochloride (C₁₇H₁₉NO₄ · HCl) dissolved at the times specified conform to

Dissolution 〈711〉, Acceptance Table 2.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

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

Sensitivity solution: 0.357 μg/mL of USP Oxymorphone RS from the Standard solution prepared as follows. Add 20% of the total volume of

Diluent and dilute with Solution A to volume.

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Tailing factor: 0.8–1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity 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 6)

Acceptance criteria: See Table 6. Disregard any peaks less than 0.05%.

Table 6

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

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

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

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

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

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

^g 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