Capillary GCMS assay of 2-n-propyl-4-pentenoic acid (4-ene VPA) in rat plasma and urine.

A simple, sensitive and specific capillary GCMS assay method is described for the determination of a toxic metabolite of valproic acid, 2-n-propyl-4-pentenoic acid (4-ene-VPA), in rat plasma and urine. The method involves a single extraction of a small volume of plasma or urine with ethyl acetate. Extraction efficiency is virtually 100%. Derivatization with MTBSTFA reagent is extremely rapid. Calibration curves are linear in the concentration ranges of 0.5-45 micrograms/mL and 2-80 micrograms/mL in rat plasma and urine respectively. The lowest detection limit using 80 microL of plasma is 100 ng/mL. Following I.V. administration of 20 mg/kg of 4-ene-VPA, plasma levels can be monitored for 6 hours in rats. The results indicate that pharmacokinetics of 4-ene VPA are similar to those of the parent drug valproic acid (VPA) in the rat.