Liquid chromatographic determination of mexiletine and tocainide in human plasma with fluorescence detection after reaction with a modified o-phthalaldehyde reagent

A liquid chromatographic procedure for the determination of mexiletine or tocainide in human plasma is described. Plasma, after the addition of a homologue of mexiletine or of tocainide, is extracted with dichloromethane. The extract is evaporated and reconstituted in a non-aqueous o-phthalaldehyde--mercaptoethanol reagent. An aliquot of the solution is chromatographed on a reversed-phase Ultrasphere-octyl column. The peaks are detected by fluorescence (lambda ex = 350 nm and lambda em = 445 nm). The fluorescent derivatives of the drugs and internal standards are stable at room temperature and give symmetrical single peaks. Use of fluorescamine as a reagent to prepare fluorescent derivatives of mexiletine and tocainide prior to chromatography is also evaluated.