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′-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 μg mL−1 and the limit of detection was as low as 0.01 μg mL−1. The relative standard deviation for intra-day and inter-day (n = 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.