Quantification of ethosuximide in human serum by GC-MS after butyl chloroformate derivatization

A simple, sensitive and robust method for determination of anti-epileptic drug ethosuximide in human serum using GC-MS was developed and validated for clinical toxicology purposes. This method employs an emerging class of derivatization agents: alkyl chloro-formates allowing the efficient and rapid derivatization of both the amino and carboxylic groups of the tested antiepileptic drug within seconds. The derivatization protocol was optimized using the Design of Experiment, and the entire sample preparation requires less than 5 minutes. Linear calibration curves were obtained in the concentration range 0.5-150 mu g/mL, with adequate accuracy (98.0-109.0%) and precision (< 10.4%). The method was successfully applied to quantification of ethosuximide in the serum of patients in both therapeutic and toxic concentration ranges