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Capillary electrophoresis evidence of the stereoselective ketoreduction of mebendazole and aminomebendazole in echinococcosis patients
Author(s) -
Theurillat Regula,
Thormann Wolfgang
Publication year - 2008
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200700381
Subject(s) - chemistry , chromatography , mebendazole , metabolite , enantiomer , capillary electrophoresis , quantitative analysis (chemistry) , high performance liquid chromatography , extraction (chemistry) , detection limit , stereoselectivity , stereochemistry , biochemistry , ecology , biology , catalysis
An assay for the simultaneous determination of the enantiomers of hydroxymebendazole (OH‐MBZ) and hydroxyaminomebendazole (OH‐AMBZ) together with aminomebendazole (AMBZ) in human plasma is described for the first time. It is based upon liquid–liquid extraction at alkaline pH from 0.5 mL plasma followed by analysis of the reconstituted extract by CE with reversed polarity in the presence of a 50 mM, pH 4.2 acetate buffer containing 15 mg/mL sulfated β‐CD as chiral selector. For all compounds, detection limits are between 0.01 and 0.04 μg/mL, and intraday and interday precisions evaluated from peak area ratios are <6.9 and <8.5%, respectively. Analysis of 39 samples of echinoccocosis patients undergoing pharmacotherapy with mebendazole (MBZ) revealed that the ketoreduction of MBZ and AMBZ is highly stereoselective. One enantiomer of each metabolite (firstly detected peak in both cases) could only be detected. The CE data revealed that OH‐MBZ (mean: 0.715 μg/mL) is the major metabolite followed by AMBZ (mean: 0.165 μg/mL) and OH‐AMBZ (mean: 0.055 μg/mL) whereas the MBZ plasma levels (mean: 0.096 μg/mL, levels determined by HPLC) were between those of AMBZ and OH‐AMBZ.