High-performance liquid chromatographic determination of valproic acid in plasma using a micelle-mediated pre-column derivatization.

A method for the determination of valproic acid (2-propylpentanoic acid) in plasma by high-performance liquid chromatography (HPLC) after pre-column derivatization is described. The derivatization of valproic acid with a fluorophore and UV label, 4-bromomethyl-7-methoxycoumarin, is performed in plasma diluted with an aqueous micellar system. No extraction or solvent evaporation steps are required. The mechanism of the derivatization of the carboxylic acid is based on phase-transfer catalysis. The sample preparation, including the derivatization step, is rapid and very simple. The proposed HPLC-method was evaluated and compared with a standard immunological assay used for the determination of valproic acid in plasma.