ABSTRACT
Albendazole (ABZ) is a benzimidazole anthelmintic drug used in the treatment of neurocysticercosis. After oral administration, ABZ is rapidly oxidized to albendazole sulfoxide (ABZSO), which has an asymmetric sulfur center, and later to albendazole sulfone (ABZSO2). ABZSO is the active metabolite responsible for the therapeutic effect of the drug. Previous studies have demonstrated pharmacokinetic differences between the two enantiomers, with the predominance of (+)-ABZSO in human biological fluids. This article describes for the first time the enantioselective analysis of ABZSO in cerebrospinal fluid (CSF) using capillary electrophoresis. The samples were prepared by liquid-liquid extraction using chloroform:isopropanol (8:2 v/v). The resolution of ABZSO enantiomers was obtained with a fused-silica capillary (60 cm x 75 microm ID) using 20 mmol/L Tris, pH 7.0, with 3.0% w/w sulfated beta-cyclodextrin as running buffer. The coefficient of variations and % relative error obtained for both within-day and between-days assays were lower than 15%. The method was linear over the concentration range of 100 to 2,500 ng/mL for each enantiomer, indicating that it is suitable for the analysis of ABZSO enantiomers in CSF from patients medicated with ABZ.
Subject(s)
Albendazole/analogs & derivatives , Albendazole/cerebrospinal fluid , Anthelmintics/cerebrospinal fluid , Electrophoresis, Capillary/methods , beta-Cyclodextrins , 2-Propanol , Chloroform , Cyclodextrins , Humans , Indicators and Reagents , Quality Control , Reproducibility of Results , Sensitivity and Specificity , StereoisomerismABSTRACT
A high-performance liquid chromatographic method has been developed for the simultaneous determination of albendazole sulfoxide (ABZSO) enantiomers and albendazole sulfone (ABZSO2) in human plasma. The resolution of ABZSO enantiomers and ABZSO2 was obtained on a Chiralpak AD column using hexane-isopropanol-ethanol (81:14.25:4.75, v/v/v) as the mobile phase. The drugs were detected by fluorescence (lambda(exc) = 280 nm, lambda(em) = 320 nm). The drugs were extracted from 500 microl plasma with ethyl acetate, and after solvent evaporation, the residues were dissolved in the mobile phase and chromatographed. The method was precise and accurate for the three compounds, as judged by the coefficients of variation and relative errors observed. Linear standard curves were obtained in the concentration range of 5-2500 ng/ml for ABZSO enantiomers and 1-500 ng/ml for ABZSO2. A typical plasma concentration-time profile is presented for one patient under treatment for neurocysticercosis.
Subject(s)
Albendazole/analogs & derivatives , Albendazole/blood , Antiparasitic Agents/blood , Albendazole/chemistry , Albendazole/therapeutic use , Antiparasitic Agents/chemistry , Antiparasitic Agents/therapeutic use , Chromatography, High Pressure Liquid , Cysticercosis/blood , Cysticercosis/drug therapy , Humans , Reproducibility of Results , Sensitivity and Specificity , StereoisomerismABSTRACT
We present a method for the enantioselective analysis of albendazole sulfoxide (ABZSO) in plasma for application in clinical pharmacokinetic studies. ABZSO enantiomers were separated on a 5-micron Chiralcel OB-H column (4.6 x 150 mm) using hexane:ethanol (93:7, v/v) as the mobile phase and fluorescence detection. ABZSO was extracted with chloroform:isopropanol (8:2, v/v) from 500-microliter aliquots of acidified plasma, with full drug recovery. The proposed method presented quantitation limits of 20 ng/ml for (-)ABZSO and 50 ng/ml for (+)ABZSO and was linear up to a concentration of 5,000 ng/ml of each enantiomer.