Morphine Sulfate Extended-Release Capsules
DEFINITION
Morphine Sulfate Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O].
IDENTIFICATION
• B.
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
Diluent:
Water. Adjust with phosphoric acid to a pH of 3.6.
Buffer solution:
13.8 mg/mL of monobasic sodium phosphate
Solution A:
Acetonitrile, triethylamine, Buffer solution, and water (25: 0.5: 100: 874.5). Adjust with phosphoric acid to a pH of 3.6.
Solution B:
Acetonitrile
Mobile phase:
See the gradient table below.
System suitability solution:
400 µg/mL of USP Morphine Sulfate RS, 10 µg/mL of USP Morphine Related Compound A RS, and 10 µg/mL of USP Morphine Related Compound B RS (pseudomorphine) in Diluent
Standard solution:
1.0 mg/mL of USP Morphine Sulfate RS in Diluent
Sample stock solution:
Transfer a weighed portion of the contents from NLT 20 Capsules, equivalent to 250 mg of morphine sulfate, to a 100-mL volumetric flask. Add 5 mL of methanol, and mix well for 30 min with gentle swirling every 5 min. Add Diluent up to half of the flask volume, and sonicate for 5 min to dissolve. Dilute with Diluent to volume.
Sample solution:
1.0 mg/mL of morphine sulfate from Sample stock solution in Diluent. Pass through a suitable filter, and use the clear filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 245 nm
Guard column:
Packing L1
Column:
3.9-mm × 30-cm; 10-µm packing L1
Flow rate:
2 mL/min
Injection size:
40 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between the morphine related compound A and morphine sulfate peaks, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of (C17H19NO3)2·H2SO4·5H2O in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
pH 7.5 phosphate buffer:
6.8 mg/mL of monobasic potassium phosphate and 1.6 mg/mL of sodium hydroxide. Adjust with phosphoric acid or 2 N sodium hydroxide to a pH of 7.5.
Medium:
Proceed as directed for Procedure for Method B under Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, observing the following exceptions. Perform Acid Stage testing, using 500 mL of 0.1 N hydrochloric acid for 1 h; and perform Buffer Stage testing, using 500 mL of pH 7.5 phosphate buffer for NLT 8 h.
Apparatus 1:
100 rpm
Times:
1, 4, 6, and 9 h
Determine the amount of (C17H19NO3)2·H2SO4·5H2O dissolved by using the following method.
Mobile phase:
Methanol, glacial acetic acid, and water (280:10:720),USP35 containing 0.73 g of sodium 1-heptanesulfonate for each 1.01 L of the solvent mixtureUSP35
System suitability solution:
0.1 mg/mL each of phenol and USP Morphine Sulfate RS in Mobile phase
Standard solution:
USP Morphine Sulfate RS in pH 7.5 phosphate buffer to obtain a solution having a known concentration corresponding to that of the Sample solution
Sample solution:
Sample per Dissolution 711.
Chromatographic system
Mode:
LC
Detector:
UV 284 nm
Column:
3.9-mm × 30-cm; 10-µm packing L1
Flow rate:
2 mL/min
Injection size:
25 µL
System suitability
Sample:
System suitability solution
[NoteThe relative retention times for phenol and morphine sulfate are about 0.8 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between the phenol and morphine sulfate peaks
Tailing factor:
NMT 2.0 for the morphine sulfate peak
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Tolerances:
The percentage of the labeled amount of (C17H19NO3)2·H2SO4·5H2O dissolved in 1 h conforms to Dissolution 711, Extended-Release Dosage Forms, Acceptance Table 3. The percentages of the labeled amount of (C17H19NO3)2·H2SO4·5H2O dissolved at the other times specified conform to Dissolution 711, Extended-Release Dosage Forms, Acceptance Table 2.
• Uniformity of Dosage Units 905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Diluent, Solution A, System suitability solution, Standard solution, Chromatographic system, and Sample solution:
Proceed as directed in the Assay.
Sensitivity solution:
0.5 µg/mL of USP Morphine Sulfate RS in Diluent
System suitability
Samples:
System suitability solution, Standard solution, and Sensitivity solution
Suitability requirements
Resolution:
NLT 2.0 between the morphine related compound A and morphine sulfate peaks, System suitability solution
Sensitivity:
Morphine peak is detectable, Sensitivity solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Diluent and Sample solution
[NoteDisregard the peaks corresponding to those obtained in the chromatogram of the Diluent. ]
Calculate the percentage of each impurity in the portion of Capsules taken:
Result = (rU/rS) × (1/F) × 100
Acceptance criteria
Any individual impurity:
See Impurity Table 1.
Total impurities:
NMT 1.5%
Impurity Table 1
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at controlled room temperature.
• USP Reference Standards 11
USP Morphine Related Compound A RS
7,8-Didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol, N-oxide. C17H19NO4 301.34
USP Morphine Related Compound B RS
2,2¢-Bimorphine. C34H36N2O6 568.66
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3955
Pharmacopeial Forum: Volume No. 36(2) Page 422
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