Simultaneous determination of topiramate, carbamazepine, oxcarbazepine and its major metabolite in human plasma by SFC-ESI-MS/MS with polarity switching: Application to therapeutic drug monitoring

Abstract

Antiepileptic drugs are the first choice for epilepsy treatment. Monitoring antiepileptic drugs is important to minimize their adverse side effects by choosing the optimum drug dosage. An accurate and high throughput supercritical fluid chromatography-tandem mass spectrometry method has been developed for the simultaneous quantification of several antiepileptic drugs in human plasma. Plasma samples were extracted with ethyl acetate and the upper organic layer was directly injected into the supercritical fluid chromatography/mass spectrometry (SFC-MS/MS) system without further nitrogen evaporation and subsequent reconstitution. The analytes were eluted on a UPC2TM BEH, 2-EP column (100 × 3 mm, 1.7 μm) at a flow rate of 1.0 mL/min and multi-reaction monitoring (MRM) was performed for determination of the analytes and internal standard (IS) in polarity switching mode. Calibration curves were linear over the concentration ranges of 0.08–40, 0.01–15, 0.01–8 and 0.5–50 μg/mL with lower limit of quantifications of 0.08, 0.01, 0.01 and 0.50 μg/mL for topiramate, carbamazepine, oxcarbazepine and monohydroxycarbamazepine, respectively. This sensitive, accurate, novel method will be very useful for monitoring the above antiepileptic drugs and for pharmacokinetic studies. Keywords: Antiepileptic drugs, SFC-ESI-MS/MS, Human plasma, Therapeutic drug monitoring