Primidone
(prim' i done).
C12H14N2O2 218.25 4,6(1H,5H)-Pyrimidinedione, 5-ethyldihydro-5-phenyl-; 5-Ethyldihydro-5-phenyl-4,6(1H,5H)-pyrimidinedione [125-33-7]. DEFINITION
Primidone contains NLT 98.0% and NMT 102.0% of C12H14N2O2, calculated on the dried basis.
IDENTIFICATION
• A. Infrared Absorption 197K:
If a difference appears, dissolve portions of both the sample and the Reference Standard in alcohol, evaporate the solutions to dryness, and repeat the tests.
• B.
The retention time of the major peak in the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
6.8 g/L of monobasic potassium phosphate
Mobile phase:
Methanol, tetrahydrofuran, and Solution A (35:0.5:65)
Diluent:
Methanol and water (35:65)
Standard stock solution:
0.5 mg/mL of USP Primidone RS in methanol
Standard solution:
0.05 mg/mL of USP Primidone RS in Diluent, prepared from the Standard stock solution
Sample stock solution:
0.5 mg/mL of Primidone in methanol
Sample solution:
0.05 mg/mL of Primidone from the Sample stock solution diluted with Diluent
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 10-cm; 3-µm packing L1
Column temperature:
35
Flow rate:
1.3 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 3000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C12H14N2O2 in the portion of Primidone taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%102.0% on the dried basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.2%
Organic Impurities
• Procedure
Solution A:
1.36 g/L of monobasic potassium phosphate
Solution B:
Methanol
Mobile phase:
See the gradient table below.
Standard stock solution:
1000 µg/mL of USP Primidone RS in methanol
Standard solution:
1 µg/mL of USP Primidone RS in methanol, prepared from the Standard stock solution in methanol
System suitability solution:
1000 µg/mL of USP Primidone RS and 10 µg/mL each of USP Phenobarbital RS and USP Primidone Related Compound C RS. Prepare by diluting weighed quantities of USP Phenobarbital RS and USP Primidone Related Compound C RS with the Standard stock solution.
Sample solution:
1000 µg/mL of Primidone in methanol
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 10-cm; monolithic packing L1
Flow rate:
3.2 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 2.5 between phenobarbital and primidone related compound C, System suitability solution
Tailing factor:
NMT 2.0 for primidone, Standard solution
Relative standard deviation:
NMT 5.0% for primidone, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Identify the impurities using the relative retention times listed in Impurity Table 1. Calculate the percentage of each impurity in the portion of sample taken:
Result = (rU/rS) × (CS/CU) × (100/F)
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.5%
[NoteDisregard impurity peaks below 0.05%. ]
Impurity Table 1
SPECIFIC TESTS
• Loss on Drying 731:
Dry a sample at 105 for 2 h: it loses NMT 0.5% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
• USP Reference Standards 11
USP Primidone Related Compound C RS
2-Phenylbutyramide. C10H13NO 163.22
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4414
Pharmacopeial Forum: Volume No. 35(3) Page 571
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