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

Abstract

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 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 degrees 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.

Sensitive chiral analysis by capillary electrophoresis

“…Offline LLE has been employed for the extraction and preconcentration of drugs in biological samples and pollutants in culture media. The detection up to 10 28 -10 26 M of drugs (such as disopyramide, praziquantel, fluoxetine, ibuprofen, ketoprofen, tramadol, and ofloxacin) in plasma [73][74][75][76], serum [75,77], and cells [78], and up to micromolar concentrations of the persistent pollutants polychlorinated biphenyls or of thiobencarb sulfoxide in culture media [79,80] has been performed. Although much less used, as it can be observed in Table 2, SLE, LPME, and microdialysis have also been employed for the preparation of samples for sensitive chiral CE.…”

Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography

“…In this paper, a direct CE method for the enantioselective analysis of IBU in plasma is reported using sulfated b-CD, a powerful chiral selector that has shown great potential for the enantiomeric separation of a series of pharmaceutical compounds [28,[39][40][41][42][43], but not yet used for the analyses of IBU enantiomers. The validated method was applied to real plasma samples from a volunteer and showed the required efficiency and selectivity for monitoring levels of 200 ng mL -1 of (2)-(R)-and (1)-(S)-IBU.…”

Enantioselective analysis of omeprazole in pharmaceutical formulations by chiral high-performance liquid chromatography and capillary electrophoresis

“…25 Sulfated β-CD has been successfully used by our group for the enantiomeric separation of a series of pharmaceutical compounds. [26][27][28][29] 321…”