Determination of tocainide in human plasma by gas chromatography with nitrogen-selective detection after Schiff base...

Tocainide is a primary amine with antiarrhythmic properties derived from lidocaine. For biopharmaceutical and pharmacokinetic purposes an assay was developed that made use of Schiff base formation with methyl isobutyl ketone and gas chromatography with nitrogen-selective detection. The derivatization procedure was performed at 85 C for 10 min, although a longer time at this temperature caused degradation of the product. Of several structural analogues the p-methyl one was the internal standard of choice. The amine was extracted from alkaline samples with dichloromethane and, after evaporation, reconstituted in methyl isobutyl ketone. From plasma the yields were lower than those from aqueous samples but the addition of hydroxylamine 30 min before the extraction process resulted in the same yields. Hydroxylamine probably acts as a competitor for carbonyl groups in the biological sample. In addition to the enhanced yields patients' samples extracted after hydroxylamine treatment were analysed with better precision. With nitrogen-selective detection 500 nmol/l in a 0.5-ml sample could be quantified, which is well below the therapeutic levels. The method compared favourably with a liquid chromatography assay.