Primidone

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Primidone contains NLT 98.0% and NMT 102.0% of C₁₂H₁₄N₂O₂, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K▲ (CN 1-May-2020):

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.

3 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

(See Chromatography 〈621〉, System Suitability.)

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%

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

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

(See Chromatography 〈621〉, System Suitability.)

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 = (rᵢ / rₛ) × (Cₛ / Cᵤ) × (100 / F)

rᵢ = 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

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.

4 SPECIFIC TESTS

Loss on Drying 〈731〉:

Dry a sample at 105° for 2 h: it loses NMT 0.5% of its weight.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Phenobarbital RS

USP Primidone RS

USP Primidone Related Compound C RS

2-Phenylbutyramide.

C₁₀H₁₁NO 163.22