Chiral analysis of albendazole sulfoxide enantiomers in human plasma and saliva using capillary electrophoresis with on-column absorption and fluorescence detection

Abstract

The capillary zone electrophoresis (CZE) analysis of albendazole sulfoxide (ABZSO) enantiomers, oxfenbendazole (OxBZ) enantiomers, and albendazole sulfone in a neutral buffer containing sulfated β-Cyclodextrin as chiral selector and having UV absorption and fluorescence detection is described. For analysis of ABZSO enantiomers in plasma and saliva, the first detected enantiomer of OxBZ is employed as internal standard and the analytes are extracted using dichloromethane. With 1 mL of plasma or saliva and reconstitution of the dried extract into 50 μL of five-fold diluted buffer without chiral selector, ABZSO enantiomer concentrations as low as 0.10 μg/mL can be determined. The assay is shown to be reproducible, robust, and suitable for analysis of ABZSO enantiomers in human plasma and saliva collected from patients that are under albendazole pharmacotherapy for the treatment of echinococcosis of the liver. Chiral analysis of extracts of 31 patient plasma samples revealed a mean (SD) enantiomeric (–)-ABZSO/(+)-ABZSO ratio of 0.31 (0.16), confirming the stereoselectivity of the albendazole metabolism in man. The mean (SD) of the (–)-ABZSO, (+)-ABZSO, and total ABZSO concentrations were determined to be 0.48 (0.45), 1.52 (0.80), and 1.96 (1.18) μg/mL, respectively. Furthermore, data obtained for five saliva samples that were collected at the time of blood withdrawal suggest that both the concentration of the ABZSO enantiomers and the enantiomeric ABZSO ratio are smaller compared to plasma.