Simultaneous plasma levels determination of mexiletine and one of its metabolites by electron capture gas-liquid chromatography.

A sensitive and specific electron capture gas-liquid chromatographic method is developed for the determination in human plasma both of mexiletine and of one of its hydroxymethyl metabolites appearing progressively during the kinetics and the presence of which is characterized by mass spectrometry. This method involves the use of two internal standards and the extraction of the drug and of its metabolite from alkaline plasma with diethyl ether followed by back extraction into sulfuric acid (0.2 N) for clean-up procedure and re-extraction by diethyl ether. The limits of detection of the heptafluorobutyryl derivatives of mexiletine and of its metabolite are 20 and 7 ng/ml of plasma, respectively. The preliminary results of the pharmacokinetic study performed in a cardiological unit after single oral administration and during long-term oral maintenance therapy are described in this paper. The method makes it possible to get a better knowledge of the kinetic behaviour of mexiletine and of its metabolite and contributes to the understanding of the origins of the variable pharmacokinetics of mexiletine in patients.