HPLC Method with Precolumn Phenacylation for the Assay of Valproic Acid and Its Salts in Pharmaceutical Dosage Forms

A simple, accurate and reproducible HPLC method is described for the assay of valproic acid and its sodium salts in commercial dosage forms. The analyte and sodium caproate, the internal standard, were detected in the UV range after formation of the corresponding phenacyl ester derivatives with a mixture of phenacyl bromide-triethylamine in acetone. The ester derivatives were analyzed directly on a Microsorb-MV C18 column with a mobile phase composed of acetonitrile-methanol-water (50:20:30) and detection at 245 nm. At a flow rate of 2 mL/min, phenacyl caproate and phenacyl valproate eluted at about 4.5 min and 8.5 min, respectively. Peak height ratios were linearly related to amounts of valproic acid, or its equivalent in sodium valproate, in the range 30–750 μg (r = 0.9997). Based on peak height ratios, the RSD for a set of replicate injections was 1.10% (n = 6). Recoveries of valproic acid or sodium valproate from spiked commercial dosage forms were in the range 101.0–102.6% of added (n = 2). The proposed HPLC method yielded assay values that were in good agreement with those obtained by the GC method for valproic acid in USP 23.