Direct separation of albendazole sulfoxide enantiomers by liquid chromatography on a chiral column deriving from (S)‐ N ‐(3,5‐dinitrobenzoyl)tyrosine: application to enantiomeric assays on plasma samples

The direct enantiomeric resolution of albendazole sulfoxide (SOABZ), an anthelmintic drug belonging to the benzimidazole class, is reported on a chiral stationary phase (CSP) synthesized by covalent binding of (S)‐ N ‐(3,5‐dinitrobenzoyl)tyrosine‐ O ‐(2‐propen‐1‐yl) methyl ester on a γ‐mercaptopropylsilanized silica gel. A comparison with the resolution achieved on commercially available Pirkle‐type CSPs obtained from N ‐(3,5‐dinitrobenzoyl) derivatives of (R)‐phenyglycine or (S)‐phenylalanine is described. Some structurally related chiral sulfoxides including oxfendazole (SOFBZ) are also studied. Optimization of the mobile phase nature and composition is investigated showing that a hexane–dioxane–ethanol ternary mixture affords an almost baseline resolution ( R s = 1.25); however, in this case, albendazole sulfone (SO 2 ABZ) is eluted between the two sulfoxide enantiomers; accordingly, a hexane–ethanol mobile phase would be preferred for biological samples containing both metabolites. The influence of temperature on the resolution is depicted with a hexane–ethanol mobile phase. Finally, application to the enantiomeric assays of SOABZ in plasmatic extracts of rat, sheep, bovin, and man after oral administration of albendazole (sulfoxidized to SOABZ and SO 2 ABZ) is reported. Some distortions in the enantiomeric ratios are evidenced depending on the species.