High-performance liquid chromatographic assay of zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in human plasma using a solid-phase extraction technique

A selective and sensitive liquid chromatographic method was developed for the determination of zonisamide in small volumes of plasma. Zonisamide and the internal standard methyl 4-hydroxybenzoate were extracted from 0.2 mL of plasma with solid-phase extraction columns and eluted with methanol. Analysis of the extracts was performed on a Symmetry C₁₈ column with ultra-violet spectrophotometric detection. The calibration curve was linear over the concentration range of 0.05-5 μg mL^-1 in plasma. Recoveries were reasonable for routine analyses; the limit of quantification was 0.05 μg mL^-1 with a signal-to-noise ratio of 5. This method could be useful for the pharmacokinetic study of zonisamide in a limited volume of human plasma and for therapeutic drug monitoring.