Valproic Acid Capsules

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

Valproic Acid Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of valproic acid (C₈H₁₆O₂).

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.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: 3.5 g/L of monobasic sodium phosphate in water. Adjust with phosphoric acid to a pH of 3.5.

Mobile phase: Acetonitrile and Buffer (45:55)

Diluent: Acetonitrile and water (45:55)

System suitability solution: 0.5 mg/mL of USP Valproic Acid RS and 50 µg/mL of USP Valproic Acid Related Compound B RS in Diluent

Standard solution: 0.5 mg/mL of USP Valproic Acid RS in Diluent

Sample solution: Nominally 0.5 mg/mL of valproic acid from the contents of the Capsules in Diluent, prepared as follows. Transfer a suitable portion of the contents of NLT 20 Capsules to an appropriate volumetric flask, and dilute with Diluent to volume. Sonicate the resulting solution for 5 min. Alternatively, stir the resulting solution for 1 h. Centrifuge a portion of the solution for about 10 min.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 215 nm. For Identification test B, use a diode array detector in the wavelength range of 200–300 nm.
• Column: 4.6-mm × 15.0-cm; 5-µm packing L7
• Flow rate: 1 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for valproic acid related compound B and valproic acid are 0.90 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between valproic acid related compound B and valproic acid, System suitability solution
• Tailing factor: NMT 1.5, Standard solution
• Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valproic acid (C₈H₁₆O₂) in the portion of Capsules 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 Valproic Acid RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: 5 mg/mL of sodium lauryl sulfate in simulated intestinal fluid TS (prepared without the enzyme and with monobasic sodium phosphate instead of monobasic potassium phosphate), adjusted with 5 M sodium hydroxide to a pH of 7.5; 900 mL

Apparatus 2: 50 rpm

Time: 60 min

Buffer, Mobile phase, Diluent, System suitability solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard stock solution: 1.5 mg/mL of USP Valproic Acid RS in Diluent, prepared as follows. Transfer NLT 150 mg of USP Valproic Acid RS to a suitable volumetric flask. Add 10% of the flask volume of Diluent and dissolve the valproic acid. Dilute with Diluent to volume.

Standard solution: 0.3 mg/mL of USP Valproic Acid RS from the Standard stock solution and Medium

Sample solution: Pass a portion of the solution through suitable filter of 0.45-µm pore size and use the filtrate.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valproic acid (C₈H₁₆O₂) dissolved:

Result = (rᵤ/rₛ) × Cₛ × (V/L) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Capsule)

Tolerances: NLT 85% (Q) of valproic acid (C₈H₁₆O₂) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉 

Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Valproic Acid RS

USP Valproic Acid Related Compound B RS

(2RS)-2-(1-Methylethyl)pentanoic acid.

C₈H₁₆O₂  144.21