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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 antiarrhythmic drug disopyramide and its main metabolite mono‐N‐dealkyldisopyramide in human plasma by capillary electrophoresis employing the cyclodextrin‐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 β‐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°C. The calibration curves were linear over the concentration range of 62.5–1850 ng/mL and 125–1850 ng/mL for each enantiomer of disopyramide and mono‐N‐dealkyldisopyramide. The mean recoveries for disopyramide and mono‐N‐dealkyldisopyramide enantiomers were up to 87 and 69%, respectively. All four enantiomers studied could be quantified at three different concentrations (200, 400 and 600 ng/mL) with coefficient of variation and % relative error not higher than 15%. The quantitation limit was 62.5 ng/mL for (+)‐(S)‐and (–)‐(R)‐disopyramide and (–)‐(R)‐mono‐N‐dealkyldisopyramide and 125 ng/mL for (+)‐(S)‐mono‐N‐dealkyldisopyramide, using 1 mL of human plasma.