Enantioselective analysis of disopyramide and mono-N-dealkyldisopyramide in plasma and urine by high-performance liquid chromatography on an amylose-derived chiral stationary phase

An enantioselective high-performance liquid chromatography method was devel oped for the simultaneous determination of disopyramide (DP) and mono-N-dea lkyldisopyramide (MND) enantiomers in plasma and urine. The drugs were extr acted from plasma samples by liquid-liquid extraction with dichloromethane after protein precipitation with trichloroacetic acid; the urine samples we re processed by Liquid-liquid extraction with dichloromethane. The enantiom ers were resolved on a Chiralpak AD column using hexane-ethanol (91:9, v/v) plus 0.1% diethylamine as the mobile phase and monitored at 270 nm. Under these conditions the enantiomeric fractions of the drug and of its metaboli te were analyzed within 20 min. The extraction procedure was efficient in r emoving endogenous interferents and low values for the relative standard de viations were demonstrated for both within-day and between-day assays. The method described in this paper allows the determination of DP and MND enant iomers at plasma levels as low as 12.5 ng/ml and can be used in clinical ph armacokinetic studies. (C) 2000 Elsevier Science B.V. All rights reserved.