Primidone Tablets

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

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

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1 DEFINITION

Primidone Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of primidone (C₁₂H₁₄N₂O₂).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

▲B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-Dec-2022)

3 ASSAY

Change to read:

Procedure

Buffer: 6.8 g/L of monobasic potassium phosphate ▲in water▲ (USP 1-Dec-2022)

Mobile phase: Methanol, tetrahydrofuran, and Buffer (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 from the Standard stock solution in Diluent

Sample stock solution: ▲Nominally 1 mg/mL of primidone prepared as follows. Finely powder Tablets (NLT 20) and transfer a portion of the powder to an appropriate volumetric flask. Add methanol to about 50% of the flask volume, sonicate, and shake by mechanical means until all of the solid is dispersed. Allow the solution to cool to room temperature, and dilute with methanol to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size and discard the first 5 mL of the filtrate.▲ (USP 1-Dec-2022)

Sample solution: 0.05 mg/mL of primidone from the ▲Sample▲ (ERR 1-Dec-2022) stock solution in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm. ▲For Identification B, use a diode array detector in the range of 200–400 nm.▲ (USP 1-Dec-2022)

Column: 4.6-mm × 10-cm; 3-µm packing L1

Column temperature: 35°

Flow rate: 1.3 mL/min

Injection volume: 20 µL

▲Run time: NLT 2.5 times the retention time of primidone▲ (USP 1-Dec-2022)

System suitability

Sample: Standard solution

Suitability requirements

▲

▲ (USP 1-Dec-2022)

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of primidone (C₁₂H₁₄N₂O₂) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response ▲of primidone▲ (USP 1-Dec-2022) from the Sample solution

rₛ = peak response ▲of primidone▲ (USP 1-Dec-2022) from the Standard solution

Cₛ = concentration of USP Primidone RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of primidone in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 60 min

Standard solution: ▲L/900 (mg/mL) of▲ (USP 1-Dec-2022) USP Primidone RS in Medium, ▲where L is the label claim in mg/Tablet▲ (USP 1-Dec-2022)

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary, to obtain a concentration that is similar to that of the Standard solution.

Instrumental conditions

Mode: UV

Analytical wavelength: 257 nm

[Note—Perform baseline corrections, if necessary, in determining the absorbance by extrapolating the baseline through the absorbance minima at 300 nm and 280 nm and beyond 257 nm.]

▲Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of primidone (C₁₂H₁₄N₂O₂) dissolved:

Result = (Aᵤ / Aₛ) × Cₛ × D × V × (1/L) × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

Cₛ = concentration of USP Primidone RS in the Standard solution (mg/mL)

D = dilution factor of the Sample solution, if needed

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)▲ (USP 1-Dec-2022)

Tolerances: NLT 75% (Q) of the labeled amount of primidone (C₁₂H₁₄N₂O₂) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Buffer, Mobile phase, and Diluent▲

▲ (USP 1-Dec-2022): Prepare as directed in the Assay.

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 from Primidone related compound A stock solution in Diluent

Standard stock solution: 0.05 mg/mL of USP Primidone RS in methanol

System suitability solution: ▲1 µg/mL of USP Primidone Related Compound A RS from the Primidone related compound A solution and 2 µg/mL of USP Primidone RS from the Standard stock solution in Diluent▲ (USP 1-Dec-2022)

Standard solution: 2 µg/mL of USP Primidone RS from the Standard stock solution in Diluent

▲Sensitivity solution: 0.5 µg/mL of USP Primidone RS from the Standard solution in Diluent▲ (USP 1-Dec-2022)

Sample solution: ▲Nominally 1000 µg/mL of primidone prepared as follows. Finely powder Tablets (NLT 20) and transfer a portion of the powder to an appropriate volumetric flask. Add methanol to about 36% of the flask volume, sonicate, and shake by mechanical means until all of the solid is dispersed. Allow the solution to cool to room temperature, and dilute with water to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size and discard the first 5 mL of the filtrate.▲ (USP 1-Dec-2022)

Chromatographic system: Proceed as directed in the Assay ▲except for the Run time.

Run time: NLT 15 times the retention time of primidone▲ (USP 1-Dec-2022)

System suitability

Samples: System suitability solution, Standard solution, ▲and Sensitivity solution▲ (USP 1-Dec-2022)

[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 related compound A and primidone, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

▲Signal-to-noise ratio: NLT 10, Sensitivity solution▲ (USP 1-Dec-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual degradation product in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵤ = peak response of each ▲degradation product▲ (USP 1-Dec-2022) from the Sample solution

rₛ = peak response ▲of primidone▲ (USP 1-Dec-2022) from the Standard solution

Cₛ = concentration of USP Primidone RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of primidone in the Sample solution (µg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

[Note—▲The reporting threshold is 0.05%.▲ (USP 1-Dec-2022)]

a 2-Phenylbutyramide.

b 2-Cyano-2-phenylbutanamide.

c ▲Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total degradation products for the drug product.▲ (USP 1-Dec-2022)

d 2-Phenylbutanoic acid.

e 5-Ethyl-5-phenyl-2-(1-phenylpropyl)dihydropyrimidine-4,6 (1H,5H)-dione.

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in well-closed containers. ▲Store at controlled room temperature.▲ (USP 1-Dec-2022)

Labeling: Tablets intended solely for veterinary use are so labeled.

Change to read:

USP Reference Standards 〈11〉

USP Primidone RS

USP Primidone Related Compound A RS

2-Ethyl-2-phenylmalonamide.

C₁₁H₁₄N₂O₂ ▲206.25▲ (USP 1-Dec-2022)