Primidone
C12H14N2O2 218.25
4,6(1H,5H)-Pyrimidinedione, 5-ethyldihydro-5-phenyl-;
5-Ethyldihydro-5-phenyl-4,6(1H,5H)-pyrimidinedione
[125-33-7].
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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.
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
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Primidone RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Primidone in the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the dried basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.2%
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.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 75 | 25 |
| 1.0 | 75 | 25 |
| 6.0 | 40 | 60 |
| 8.0 | 40 | 60 |
| 8.5 | 75 | 25 |
| 10.0 | 75 | 25 |
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)
| rU | = | = peak response of the impurity from the Sample solution |
| rS | = | = peak response of Primidone from the Standard solution |
| CS | = | = concentration of USP Primidone RS in the Standard solution (µg/mL) |
| CU | = | = concentration of Primidone in the Sample solution (µg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.5%
[Note—Disregard impurity peaks below 0.05%. ]
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Primidone related compound Aa | 0.5 | 0.67 | 0.1 |
| Phenobarbital | 1.4 | 1.0 | 0.1 |
| Primidone related compound Cb | 1.6 | 0.67 | 0.1 |
| 2-Cyano-2-phenylbutyramide | 1.8 | 0.71 | 0.1 |
| 2-Phenylbutyric acid | 2.0 | 0.77 | 0.1 |
| Phenylpropylprimidonec | 2.8 | 1.0 | 0.3 |
| Any unspecified impurity |
— | 1.0 | 0.1 |
|
a
2-Ethyl-2-phenylmalonamide (2-ethyl-2-phenylpropanediamide).
b
2-Phenylbutyramide.
c
5-Ethyl-5-phenyl-2-(1-phenylpropyl)dihydropyrimidine-4,6(1H,5H)-dione.
|
|||
SPECIFIC TESTS
• Loss on Drying 731:
Dry a sample at 105 for 2 h: it loses NMT 0.5% of its weight.
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
11
USP Phenobarbital RS 
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USP Primidone RS
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USP Primidone Related Compound C RS
2-Phenylbutyramide.
C10H13NO 163.22
2-Phenylbutyramide.
C10H13NO 163.22
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4414
Pharmacopeial Forum: Volume No. 35(3) Page 571