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

Levetiracetam is an antiepileptic drug for the treatment of psychiatric patients. In this study, a selective, straightforward, and rapid online heart-cutting LC 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 30 mM aq. ortho-phosphoric acid solution/methanol (70:30) at a flow rate of 1 mL/min for the first system and 10 mM aq. ortho-phosphoric acid solution/methanol (55:45) at a flow rate of 1 mL/min for the second system. The first separation was carried out on a GL Sciences Intersil ODS-3 column (4.6 mm × 150 mm, 3 μm) and the second separation was carried out on a Restek Ultra PFPP column (4.6 mm × 150 mm, 5 μm). The detection was carried out at 205 nm for both systems. The method was validated for selectivity and linearity, which were in the 6-60 μg/mL range. Intra-assay and inter-assay accuracies were < 112.6%, and the intra-assay and inter-assay precisions were < 6.4% for all QC samples. The lower limit of quantitation was 6 μg/mL. The developed method was successfully applied for therapeutic drug monitoring of plasma samples from patients.