Gas-chromatographic analysis for valproic acid as phenacyl esters.

We describe a novel isothermal gas-chromatographic procedure for measuring valproic acid. Plasma, with cyclohexanecarboxylic acid added as internal standard, is selectively extracted with pentane to minimize the extraction of other acidic drugs. To convert carboxylic acids to their phenacyl esters, alpha-bromoacetophenone is added to the organic extract before evaporating the solvent. These esters are relatively less volatile than the acids themselves and the extracting solvent can be removed without any loss of valproic acid or internal standard. The phenacyl esters, when chromatographed on 3% OV-17, produce sharp, well-shaped peaks and show high response for the flame ionization detector. Valproic acid is well separated from the internal standard, from reagents and plasma constituents, and from some commonly prescribed drugs that we examined. When alpha-bromo-p-nitroacetophenone is sued as the derivatizing agent, the resulting nitrophenacyl esters can be analyzed with use of a nitrogen-specific detector.