Determination of valproic acid and its metabolites by gas chromatography-mass spectrometry with selected ion monitoring.

A modified method for the determination of valproic acid, its eleven metabolites and their conjugates in small samples of serum and urine by gas chromatography-mass spectrometry with selected-ion monitoring was developed. Valproic acid and its eleven metabolites were determined in serum and urine of epileptic patients treated with valproic acid. 2-Hydroxy-2-propylpentanoic acid was identified as a new metabolite of valproic acid in the urine of 11 of the 12 patients. The unsaturated metabolites, such as (Z)- and (E)-2-propyl-2-pentenoic acid, were found to be predominantly excreted as glucuronides. 3-Hydroxy-2-propylpentanoic acid and 2-propylglutaric acid were also excreted as glucuronides.