Gas chromatography-mass spectrometry assay method for the therapeutic drugmonitoring of the antiepileptic drug tiagabine

A gas chromatography-mass spectrometry assay method suitable for the therap eutic drug monitoring of the antiepileptic drug tiagabine is described. Tia gabine and its desmethylated analogue used as internal standard were first extracted from serum by liquid-liquid extraction using an ethyl ether-isobu tanol 98:2 mixture. Tiagabine and the internal standard were then methylate d in the organic phase in presence of methanol by means of a safe and stabl e diazomethane derivative. After evaporation, the reconstituted extracts we re chromatographed on a crosslinked phenyl methyl siloxane capillary column and detected by mass fragmentometry at m/z = 156. No other antiepileptic d rug possibly administrated in polytherapy and no metabolite were found to i nterfere in the assay. The limit of quantification was 5 ng/ml. The precisi on and the accuracy were found to be suitable for the therapeutic drug moni toring of tiagabine. (C) 1999 Elsevier Science B.V. All rights reserved.