Oxycodone Hydrochloride Extended-Release Tablets
DEFINITION
Oxycodone Hydrochloride Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of oxycodone hydrochloride (C18H21NO4·HCl).
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.
ASSAY
• Procedure
Buffer solution:
2 g/L of sodium heptanesulfonate in water. Add 13.3 mL/L of glacial acetic acid, and adjust with 5 N sodium hydroxide solution to a pH of 3.50 ± 0.05.
Mobile phase:
Acetonitrile and Buffer solution (1:3)
Standard solution:
0.036 mg/mL of USP Oxycodone RS in Mobile phase
Sample stock solution:
Transfer 10 Tablets into an appropriate volumetric flask, add a volume of a mixture of methanol and acetonitrile (1:1), equivalent to 50% of the volumetric flask volume, sonicate for 10 min, and stir for 20 min. Dilute with Buffer solution to volume.
Sample solution:
0.04 mg/mL of oxycodone hydrochloride, from the Sample stock solution, diluted with Mobile phase to volume. Pass through a suitable filter.
Chromatographic system
Mode:
LC
Detector:
UV 280 nm
Column:
4.6-mm × 15-cm; packing L1
Flow rate:
1.0 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 4000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C18H21NO4·HCl in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Oxycodone RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of oxycodone hydrochloride, 351.82 |
| Mr2 | = | = molecular weight of oxycodone base, 315.37 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Test 1
Medium:
Simulated gastric fluid (without enzymes); 900 mL
Apparatus 1:
100 rpm
Time:
1, 2, 4, 6, and 8 h for Tablets labeled to contain 10, 20, or 40 mg; 1, 2, 4, and 6 h for Tablets labeled to contain 80 mg
Standard stock solution
Tablets labeled to contain 10 mg:
398 µg/mL of USP Oxycodone RS in Medium
Tablets labeled to contain 20, 40, or 80 mg:
796 µg/mL of USP Oxycodone RS in Medium
Standard solution:
Dilute the appropriate Standard stock solution with Medium to obtain solutions containing L/900 mg/mL, with L being the oxycodone Tablet label claim, in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
About 226 nm (shoulder)
Cell
For Tablets labeled to contain 10, 20, or 40 mg:
1.0 cm
For Tablets labeled to contain 80 mg:
0.5 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
For Tablets labeled to contain 10, 20, or 40 mg, calculate the amount of C18H21NO4 dissolved:
Result = [C × (AU/AS) × (V 
VS) + (C1 × VS) + (C2 × VS) + (C4 × VS) + (C6 × VS) + (C8 × VS)] × (100/L)
VS) + (C1 × VS) + (C2 × VS) + (C4 × VS) + (C6 × VS) + (C8 × VS)] × (100/L)| C | = | = concentration of the appropriate Standard solution (mg/mL) |
| AU | = | = absorbance of the solution under test |
| AS | = | = absorbance of the appropriate Standard solution |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C1 | = | = concentration of oxycodone in the Medium determined at 1 h (mg/mL) |
| C2 | = | = concentration of oxycodone in the Medium determined at 2 h (mg/mL) |
| C4 | = | = concentration of oxycodone in the Medium determined at 4 h (mg/mL) |
| C6 | = | = concentration of oxycodone in the Medium determined at 6 h (mg/mL) |
| C8 | = | = concentration of oxycodone in the Medium determined at 8 h (mg/mL) |
| L | = | = Tablet label claim (mg) |
For Tablets labeled to contain 80 mg, calculate the amount of C18H21NO4 dissolved:
Result = [C × (AU/AS) × (V VS) + (C1 × VS) + (C2 × VS) + (C4 × VS) + (C6 × VS)] × (100/L)
VS) + (C1 × VS) + (C2 × VS) + (C4 × VS) + (C6 × VS)] × (100/L)| C | = | = concentration of the appropriate Standard solution (mg/mL) |
| AU | = | = absorbance of the solution under test |
| AS | = | = absorbance of the appropriate Standard solution |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C1 | = | = concentration of oxycodone in the Medium determined at 1 h (mg/mL) |
| C2 | = | = concentration of oxycodone in the Medium determined at 2 h (mg/mL) |
| C4 | = | = concentration of oxycodone in the Medium determined at 4 h (mg/mL) |
| C6 | = | = concentration of oxycodone in the Medium determined at 6 h (mg/mL) |
| L | = | = Tablet label claim (mg) |
Tolerances:
The percentages of the labeled amount of C18H21NO4 dissolved at the times specified conform to Acceptance Table 2.
For Tablets Labeled to Contain 10, 20, or 40 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 20%–40% |
| 2 | 35%–55% |
| 4 | 55%–75% |
| 6 | 70%–90% |
| 8 | NLT 80% |
For Tablets Labeled to Contain 80 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 25%–45% |
| 2 | 45%–65% |
| 4 | 65%–85% |
| 6 | NLT 80% |
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:
Simulated gastric fluid (without enzymes); 900 mL
Apparatus 1:
100 rpm
Time:
1, 4, and 12 h
0.85% phosphoric acid:
10 mL/L of phosphoric acid in water
Standard stock solution:
0.9 mg/mL of USP Oxycodone RS in 0.85% phosphoric acid
Standard solution:
Dilute the Standard stock solution, quantitatively and stepwise, with Medium to obtain a solution having a concentration of 40% of the Tablet label claim. [Note—This solution is stable for 2 weeks at room temperature. ]
Sample solution:
Pass the solution under test through a suitable filter of 0.45-µm pore size.
Mobile phase:
Weigh 23.1 g of monobasic potassium phosphate into a 4-L flask, and dissolve with 3400 mL of water. Add 4 mL of triethylamine, and adjust with 0.85% phosphoric acid to a pH of 3.0 ± 0.1. Add 600 mL of methanol and 20 mL of tert-butyl methyl ether, and mix well.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
3.9-mm × 30-cm; 10-µm packing L1
Column temperature:
60
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Capacity factor:
NLT 0.5
Tailing factor:
0.75–1.5
Relative standard deviation:
NMT 2%
Analysis
Samples:
Standard solution and Sample solution
Calculate the amount of C18H21NO4 dissolved:
Result = [C × (rU/rS) × (V VS) + (C1 × VS) + (C4 × VS) + (C12 × VS)] × (100/L)
VS) + (C1 × VS) + (C4 × VS) + (C12 × VS)] × (100/L)| C | = | = concentration of the appropriate Standard solution (mg/mL) |
| rU | = | = peak response of the solution under test |
| rS | = | = peak response of the appropriate Standard solution |
| V | = | = initial volume of Medium in the vessel under test (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C1 | = | = concentration of oxycodone in the Medium determined at 1 h (mg/mL) |
| C4 | = | = concentration of oxycodone in the Medium determined at 4 h (mg/mL) |
| C12 | = | = concentration of oxycodone in the Medium determined at 12 h (mg/mL) |
| L | = | = Tablet label claim (mg) |
Tolerances:
The percentages of the labeled amount of C18H21NO4 dissolved at the times specified conform to Acceptance Table 2.
For Tablets Labeled to Contain 10 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 29%–49% |
| 4 | 58%–78% |
| 12 | NLT 85% |
For Tablets Labeled to Contain 20 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 33%–53% |
| 4 | 63%–83% |
| 12 | NLT 85% |
For Tablets Labeled to Contain 40 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 37%–57% |
| 4 | 68%–88% |
| 12 | NLT 85% |
For Tablets Labeled to Contain 80 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 31%–51% |
| 4 | 61%–81% |
| 12 | NLT 85% |
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure: Limit of Oxycodone Related Compound B (Oxycodone N-Oxide)
Diluent:
10 mL/L of phosphoric acid in water
Buffer:
6.8 g/L of monobasic potassium phosphate. Add 1.2 mL of triethylamine, and adjust with Diluent to a pH of 3.0 ± 0.1.
Mobile phase:
Methanol, tert-butyl methyl ether, and Buffer (30:1:170)
Standard solution:
0.18 mg/mL of USP Oxycodone RS and 0.002 mg/mL of USP Oxycodone Related Compound B RS in Diluent. [Note—Prepare fresh daily ] .
Sample stock solution:
Transfer 10 Tablets into a 500-mL volumetric flask, add 50 mL of Diluent and 50 mL of alcohol, and sonicate for 90 min to extract the active ingredient. Dilute with Diluent to volume.
Sample solution:
0.2 mg/mL of oxycodone hydrochloride from the Sample stock solution in Diluent. Pass a portion of the solution through a suitable filter, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
3.9-mm × 30-cm; 10-µm packing L1
Column temperature:
60
Flow rate:
1.0 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 4.5 between the oxycodone and oxycodone related compound B peaks
Relative standard deviation:
NMT 3.0% for oxycodone related compound B
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of oxycodone related compound B in the portion of the Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| CS | = | = concentration of USP Oxycodone Related Compound B RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oxycodone in the Sample solution (mg/mL) |
Acceptance criteria:
NMT 1%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at controlled room temperature.
• 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
11
USP Oxycodone RS 
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USP Oxycodone Related Compound B RS
4,5a-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one N-oxide.
C18H21NO5 331.36
4,5a-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one N-oxide.
C18H21NO5 331.36
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4173
Pharmacopeial Forum: Volume No. 36(5) Page 1199