Primidone Tablets
DEFINITION
Primidone Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of C12H14N2O2.
IDENTIFICATION
• 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:
Transfer an equivalent to about 250 mg of primidone, from finely powdered Tablets (NLT 20), based on the label claim, to a 250-mL volumetric flask. Add about 125 mL of methanol, sonicate for about 15 min, and shake by mechanical means until all the solid is dispersed (usually 20 min). Allow the solution to cool to room temperature, and dilute with methanol to volume. Pass a portion of this solution through a 0.45-µm PTFE (or equivalent) filter, and discard the first 5 mL of filtrate.
Sample solution:
0.05 mg/mL of primidone from the Sample stock solution in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm x 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 Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of the Sample solution |
| rS | = | = peak response of 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:
95.0%–105.0%
PERFORMANCE TESTS
• Dissolution 
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Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Time:
60 min
Detector:
UV 257 nm
Standard solution:
USP Primidone RS in Medium
[Note—Perform baseline corrections, if necessary, in determining the absorbance by extrapolating the baseline through the absorbance minima at 300 and 280 nm and beyond 257 nm. ]
Sample solution:
Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary, to a concentration that is similar to that of the Standard solution.
Tolerances:
NLT 75% (Q) of the labeled amount of C12H14N2O2 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Solution A, Mobile phase, Diluent, and Chromatographic system:
Proceed as directed in the Assay.
Primidone stock solution:
0.05 mg/mL of USP Primidone RS in methanol
Primidone related compound A stock solution:
200 µg/mL of USP Primidone Related Compound A RS in methanol
Primidone related compound A solution:
20 µg/mL of USP Primidone Related Compound A RS in Diluent, from Primidone related compound A stock solution
System suitability solution:
1 µg/mL of USP Primidone Related Compound A RS and 2 µg/mL of USP Primidone RS in Diluent, from Primidone related compound A solution and Primidone stock solution
Standard solution:
2 µg/mL of USP Primidone RS in Diluent, from Primidone stock solution
Sample solution:
Transfer an equivalent to about 250 mg of primidone, from finely powdered Tablets (NLT 20), based on the label claim, to a 250-mL volumetric flask. Add about 90 mL of methanol, sonicate for about 15 min, and shake by mechanical means until all the solid is dispersed (usually 20 min). Allow the solution to cool to room temperature, and dilute with water to volume. Pass a portion of this solution through a 0.45-µm PTFE (or equivalent) filter, and discard the first 5 mL of filtrate.
Chromatographic system
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for primidone related compound A and primidone are 0.5 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 4.0 between primidone and primidone related compound A, System suitability solution
Relative standard deviation:
NMT 5.0% for primidone, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (100/F)
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response 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.
[Note—Disregard impurity peaks that are less than 0.025%. ]
Total impurities:
NMT 0.3%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Primidone related compound Aa | 0.5 | 0.76 | 0.1 |
| Primidone | 1.0 | — | — |
| Phenobarbital | 1.6 | 1.4 | 0.1 |
| Primidone related compound Cb | 1.9 | 0.92 | 0.1 |
| 2-Phenylbutyric acid | 4.1 | 0.91 | 0.1 |
| Any unspecified impurity | — | 1.0 | 0.1 |
|
a
2-Ethyl-2-phenylmalonamide.
b
2-Phenylbutyramide.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
• Labeling:
Tablets intended solely for veterinary use are so labeled.
• USP Reference Standards 11
11
USP Primidone RS 
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USP Primidone Related Compound A RS
2-Ethyl-2-phenylmalonamide.
C11H14N2O2 206.24
2-Ethyl-2-phenylmalonamide.
C11H14N2O2 206.24
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 |
| 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 4416
Pharmacopeial Forum: Volume No. 35(3) Page 573