Liquid chromatography tandem mass spectrometry method for the estimation of lamotrigine in human plasma: Application to a pharmacokinetic study

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• 作者：Santosh Ghatol ; Vatsal Vithlani ; Sanjay Gurule ; Arshad Khuroo ; Tausif Monif ; Pankaj Partani ; ^{pankaj.partani@ranbaxy.com}
• 关键词：Lamotrigine ; Liquid chromatography/tandem mass spectrometry ; Solid phase extraction ; Pharmacokinetic study
• 刊名：Journal of Pharmaceutical Analysis
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：3
• 期：2
• 页码：75-83
• 全文大小：676 K

文摘

A reliable, selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human plasma using lamotrigine-¹³C3, d3 as an internal standard. Analyte and internal standard were extracted from human plasma by solid-phase extraction and detected in positive ion mode by tandem mass spectrometry with electrospray ionization (ESI) interface. Chromatographic separation was performed on a Chromolith^? SpeedROD; RP-18e column (50?4.6 mm i.d.) using acetonitrile: 5¡À0.1 mM ammonium formate solution (90:10, v/v) as the mobile phase at a flow rate of 0.500 mL/min. The calibration curves were linear over the range of 5.02-1226.47 ng/mL with the lower limit of quantitation validated at 5.02 ng/mL. The analytes were found stable in human plasma through three freeze (?20 ¡ãC)-thaw (ice-cold water bath) cycles and under storage on bench-top in ice-cold water bath for at least 6.8 h, and also in the mobile phase at 10 ¡ãC for at least 57 h. The method has shown good reproducibility, as the intra- and inter-day precisions were within 3.0 % , while the accuracies were within ¡À6.0 % of nominal values. The validated LC-MS/MS method was applied for the evaluation of pharmacokinetic and bioequivalence parameters of lamotrigine after an oral administration of 50 mg lamotrigine tablet to thirty-two healthy adult male volunteers.