QUANTITATIVE DETERMINATION OF LACOSAMIDE IN HUMAN PLASMA USING LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY AND ITS APPLICATION TO PHARMACOKINETIC STUDY

A simple, reliable, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of lacosamide, an antiepileptic drug, in human plasma. The lacosamide and internal standard (IS) have been extracted by a simple liquid-liquid extraction method and separated on C₁₈ (50 × 4.6 mm, 5μm) column with the mobile phase of 5mM ammonium formate and methanol (50:50, v/v), pumped at flow-rate of 0.5 mL/min. The ion transitions were monitored in positive ion mode [M+H]⁺ at m/z 251.20 >91.10 for lacosamide and m/z 256.10>211.10 for IS. Method validation revealed excellent linearity over the concentration range of 9 – 9000 ng/mL together with satisfactory intra and inter-assay precision, accuracy, and extraction recoveries. Lacosamide was found stable throughout the various sample handling and processing conditions. It is proposed to evaluate the performance of the developed method by measurement of a plasma concentration of lacosamide versus time in four epileptic patients to monitor pharmacokinetic behavior of it. The variation in estimated pharmacokinetic parameters shows the need for individual monitoring of lacosamide concentration profile in epileptic patients by the sensitive, accurate and specific method.