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This study established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to study the pharmacokinetics of four antiepileptic drugs, lamotrigine, oxcarbazepine, lacosamide, and topiramate, in rats after oral administration. The gradient elution was performed on a UPLC HSS T3 (2.1 mm × 100 mm, 1.8 μm) column with acetonitrile-0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min. Protein precipitation by acetonitrile was adopted for plasma sample pretreatment. Electrospray- (ESI-) positive/negative ion switching and multiple reaction monitoring (MRM) modes were adopted for ion quantitative determination of antiepileptic drugs. UPLC-MS/MS detection and Drug and Statistics (DAS) software fitting were performed to blood samples collected from rats after oral administration of lamotrigine, oxcarbazepine, lacosamide, and topiramate (5 mg/kg). All drugs examined showed linearity within 5–5000 ng/ml (R2 &gt; 0.9987), the intraday accuracy was within 92%–108%, and the interday accuracy was within 93%–109%. The relative standard deviations (RSD) of intraday and interday were less than 15%. The matrix effect was within 91%–105%, and the recovery was better than 88%. The established UPLC-MS/MS method was successfully applied to the pharmacokinetic study of lamotrigine, oxcarbazepine, lacosamide, and topiramate in rats.

international journal of analytical chemistry

Simultaneous Determination of Lamotrigine, Oxcarbazepine, Lacosamide, and Topiramate in Rat Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry