Valproate Sodium Injection

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

Valproate Sodium Injection is a sterile aqueous solution of sodium valproate, formed from the interaction of Valproic Acid and Sodium Hydroxide, in Water for Injection, and one or more suitable buffering or sequestering agents. It contains NLT 90.0% and NMT 110.0% of the labeled amount of valproic acid (C₈H₁₆O₂). It contains no antimicrobial agents.

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.

Change to read:

C. Identification Tests-General 〈191〉, Chemical Identification Tests, Sodium: Meets the requirements

3 ASSAY

Change to read:

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 water from a suitable volume of Injection

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 1.6 times the retention time 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 Injection 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

Bacterial Endotoxins Test 〈85〉: NMT 23 USP Endotoxin Units/mL of Injection

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume parenterals

pH 〈791〉: 7.0–9.0

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose containers as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, preferably of Type I glass. Store at controlled room temperature.

Labeling: It states the name and quantity of any buffering or sequestering agent used. It states that it is intended for use by intravenous infusion only.

USP Reference Standards 〈11〉

USP Valproic Acid RS

USP Valproic Acid Related Compound B RS

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

C₈H₁₆O₂  144.21