Simultaneous determination of disopyramide and mono-N-dealkyldisopyramide enantiomers in human plasma by capillary electrophoresis

In this paper, a rapid method for the enantioselective analysis of the anti arrhythmic drug disopyramide and its main metabolite mono-N-dealkyldisopyra mide in human plasma by capillary electrophoresis employing the cyclodextri n-modified electrokinetic chromatography mode is described. Sample clean-up was carried out by alkalinization with sodium hydroxide followed by liquid -liquid extraction with toluene. The complete enantioselective analysis was performed within less than 5 min using 20 mmol/L sodium acetate buffer, pH 5.0, containing 0.2% w/v sulfated beta -cyclodextrin as chiral selector. A 40 cm uncoated fused-silica capillary was used for the analysis, performed at a voltage of 15 kV and at 20 degreesC. The calibration curves were line ar over the concentration range of 62.5-1850 ng/mL and 125-1850 ng/mL for e ach enantiomer of disopyramide and mono-N-dealkyldisopyramide. The mean rec overies for disopyramide and mono-N-dealkyldisopyramide enantiomers were up to 87 and 69%, respectively All four enantiomers studied could be quantifi ed at three different concentrations (200, 400 and 600 ng/mL) with coeffici ent of variation and % relative error not higher than 15%. The quantitation limit was 62.5 ng/mL for (+)-(S)-and (-)-(R)-disopyramide and (-) -(R)-mon o-N-dealkyldisopyramide and 125 ng/mL for (+)-(S)-mono-N-dealkyldisopyramid e, using 1 mt of human plasma.