Divalproex Sodium

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

Divalproex Sodium contains NLT 98.0% and NMT 102.0% of available valproic acid (C₈H1₆O₂).

2 IDENTIFICATION

Change to read:

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

B. Identification Tests—General 〈191〉, Chemical Identification Tests,Sodium

Sample: 100 mg of Divalproex Sodium

Analysis: Ignite the Sample, and dissolve the residue in 2 mL of water. Proceed as indicated in the chapter, starting with “Add 2 mL”.

Acceptance criteria: Meets the requirements

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

3 ASSAY

Procedure

Buffer: 3.5 g of monobasic sodium phosphate in 900 mL of water. Adjust with phosphoric acid to a pH of 3.5. Dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (50:50)

Impurity stock solution: 0.5 mg/mL of USP Valproic Acid Related Compound A RS in acetonitrile

Standard stock solution: 5.0 mg/mL of USP Valproic Acid RS in Mobile phase

System suitability solution: 0.5 mg/mL of valproic acid from the Standard stock solution, and 5 μg/mL of valproic acid related compound A from the Impurity stock solution in Mobile phase

Standard solution: 0.5 mg/mL of USP Valproic Acid RS from the Standard stock solution in Mobile phase

Sample solution: 0.5 mg/mL of Divalproex Sodium in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.8 times the retention time of valproic acid

System suitability

Sample: System suitability solution

[Note—The relative retention times for valproic acid related compound A and valproic acid are 0.69 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 5.0 between valproic acid related compound A and valproic acid

Tailing factor: NMT 1.5 for valproic acid

Relative standard deviation: NMT 2.0% for valproic acid

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of available valproic acid (C₈H1₆O₂) in the portion of Divalproex Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × (1/M) × 100

r_U= peak area from the Sample solution

r_S= peak area from the Standard solution

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

C_U= concentration of the Sample solution (mg/mL)

M_r1= molecular weight for divalproex sodium repeating unit, 310.41

M_r2= molecular weight for valproic acid, 144.21

M = number of moles of valproic acid per mole of divalproex sodium repeating unit, 2

Acceptance criteria: 98.0%–102.0%

4 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 1.0%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Divalproex Sodium RS

USP Valproic Acid RS

USP Valproic Acid Related Compound A RS

Diallyl acetic acid;

Also known as 2-Allylpent-4-enoic acid.

C₈H1₆O₂ 140.18