Liquid chromatography coupled with tandem mass spectrometry for simultaneous quantification of valproate, valproate‐glucuronide and lamotrigine in various biological matrices of rat

Abstract

Valproate and lamotrigine are commonly used as antiepileptic drugs even in pregnant and breastfeeding women. The extent and effects of drug exposure on the developing brain of the offspring are not well understood. Animal models can be utilised to investigate the transfer of substances into fetal brain with the ultimate aim of providing insights to aid clinical decisions. In the present study, an LC-MS/MS method was developed and validated for quantification of valproate (VPA), valproate-glucuronide (VPA-Gluc, a major metabolite of valproate) and lamotrigine (LTG) in rat blood plasma, cerebrospinal fluid and brain tissue. A 10 μl sample was spiked with stable isotope-labelled internal standards and extracted by methanol.An Agilent RRHD Eclipse Plus C 18 column (2.1 Â 100 mm, 1.8 μm) was used.