Valproic Acid Oral Solution

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 Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of valproic acid (C₈H₁₆O₂). It is prepared with the aid of Sodium Hydroxide.

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.

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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

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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 in Diluent from a suitable volume of Oral Solution

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 215 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 4.6-mm × 15.0-cm; 5-µm packing L7
• Flow rate: 1 mL/min
• Injection volume: 20 µL
• Run time: NLT 2 times the retention of valproic acid

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 Oral Solution 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 SPECIFIC TESTS

pH 〈791〉: 7.0–8.0

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Valproic Acid RS

USP Valproic Acid Related Compound B RS

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

C₈H₁₆O₂  144.21