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

Erjie Qiu,Congcong Wen,Lu Yu,Qishun Liang,Victoria F Samanidou

doi:10.1155/2022/1838645

Abstract

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 > 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.

Highlights

Epilepsy is a common nervous system disease [1–3]
Instruments and Conditions. e Acquity H-Class UPLC coupled to the XEVO TQS-Micro triple quadrupole mass spectrometer (Waters Corp., Milford, MA, USA) was used for UPLC-MS/MS. e gradient elution was performed on a UPLC HSS T3 (2.1 mm × 100 mm, 1.8 μm) column (Waters Corp., Milford, MA, USA) with acetonitrile-0.1% formic acid as a mobile phase at a 0.4 mL/min flow rate. e gradient elution conditions were as follows: 0–0.2 min, acetonitrile 10%; 0.2–2.4 min, acetonitrile 10%–75%; 2.4–5.0 min, acetonitrile 75%–90%; 5.0–5.1 min, acetonitrile 90%–10%; and 5.1–6.5 min, 10% acetonitrile
Calibration curves of lamotrigine, oxcarbazepine, lacosamide, and topiramate were constructed by analyzing spiked calibration samples on three separate days. e lower limit of quantification (LLOQ) was defined as the lowest concentration on the calibration curves, and the deviation should be within ±20%

Summary

Introduction

Epilepsy treatment usually relies on antiepileptic drugs that belong to the symptom control drugs [4,5]. Most epilepsy patients require long-term medication; patients show individual differences in drug response [6–10]. To simultaneously improve the effectiveness and safety of clinical drugs and provide a reliable scientific basis for diagnosing and treating drug overdose poisoning, a rapid and accurate method is necessary to determine drug concentration in plasma. E methods for the determination of antiepileptic drugs mainly include high-performance liquid chromatography (HPLC) [11–14], immunoassay [15, 16], and gas chromatography-mass spectrometer (GC-MS) [17, 18]. Methods for measuring individual antiepileptic drug concentration have been widely reported, some patients with severe conditions require multiple drugs simultaneously. It is urgent to establish a rapid and quantitative screening method for several antiepileptic drugs to meet the clinical needs

Methods

Results

Conclusion