A New Derivatization Method to Enhance Sensitivity for the Determination of Low Levels of Valproic Acid in Human Plasma

A novel and sensitive high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of valproic acid (VPA) in human plasma. The method was based on derivatization of VPA using 2-bromo-2 0 -acetonaphthone as a new derivatization reagent. Caprylic acid was used as an internal standard (IS). Under the optimized extraction and derivatization conditions, the method showed good linearity in the range of 0.05– 200 m gm L 21 and the limit of detection was as low as 0.01 m gm L 21 . The relative standard deviation for intra-day and inter-day (n 5 5) was <5%. The recovery ranged from 95.2 to 101.4%. The proposed method is proved to be highly sensitive, simple and rapid, and was successfully applied to the analysis of VPA in plasma samples from patients with generalized epilepsy.