Determination of levetiracetam in human plasma by online heart-cutting liquid chromatography: Application to therapeutic drug monitoring.

Abstract

Levetiracetam is an antiepileptic drug for the treatment of psychiatric patients. In this study, a selective, straightforward, and rapid online heart-cutting liquid chromatography method was developed for the therapeutic drug monitoring of levetiracetam. This method allows for the determination of levetiracetam in human plasma without complex sample preparation. The mobile phases consisted of 30mM aq. orthophosphoric acid solution/methanol (70:30) at a flow rate of 1mL/min for the first system and 10mM aq. orthophosphoric acid solution/methanol (55:45) at a flow rate of 1mL/min for the second system. The first separation was carried out on a GL Sciences Intersil ODS-3 column (4.6mm × 150mm, 3µm) and the second separation was carried out on a Restek Ultra PFPP column (4.6mm × 150mm, 5µm). The detection was carried out at 205nm for both systems. The method was validated for selectivity and linearity, which were in the 6-60µg/mL range. Intra- and interassay accuracies were<112.6%, and the intra- and interassay precisions were<6.4% for all quality control samples. The lower limit of quantitation was 6µg/mL. The developed method was successfully applied for therapeutic drug monitoring of plasma samples from patients.