Fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of eight antiepileptic drugs and an active metabolite in human plasma using polarity switching and timed selected reaction monitoring.

Abstract

A fast liquid chromatography-tandem mass spectrometry method using polarity switching and timed selected reaction monitoring has been developed and validated to quantify eight antiepileptic drugs and an active drug metabolite in human plasma within a single analytical assay. The antiepileptic drugs include levetiracetam, lamotrigine, zonisamide, topiramate, carbamazepine, phenytoin, divalproex sodium, oxcarbazepine, and the oxcarbazepine active metabolite 10,11-dihydro-10-hydroxycarbamazepine. The method was validated over concentration ranges specifically for each compound, with a lower limit of quantification of 5-50\u202fng/mL. The method is accurate and precise, with intra-day and inter-day accuracy ranging from 93.7 to 104.7% and 94.1 to 107.1%, respectively, and intra-day and inter-day coefficient of variation (CV) ranging of 0.8-4.4% and 1.5-7.1%, respectively. Simple two-step protein precipitation and dilution sample preparation, high sensitivity, and high throughput make this method suitable for multi-drug monitoring for epileptic patients.