title: Capillary electrophoresis with (R)-(--)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine as chiral selector for separation of albendazole sulfoxide enantiomers and their analysis in human plasma.
abstract: The electrokinetic separation and analysis of the enantiomers of albendazole sulfoxide (ABZSO), a sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-beta-cyclodextrin. With the Pirkle-type (R)-(-)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.0-9.5 and can be detected by UV absorbance at 295 nm. Having untreated fused-silica capillaries and 50 mM (R)-DNBPG, enantiomeric resolution is dependent on capillary i.d., capillary length and operational temperature. Optimized separation is obtained for pH 9.25 and the lowest temperature setting. Preliminary data indicate that the same approach could be employed for analysis of the enantiomers of oxfenbendazole, a chiral anthelmintic sulfoxide employed in veterinary pharmacotherapy. Analysis of plasma extracts of patients under ABZ pharmacotherapy confirmed the known enantioselectivity in the sulfoxidation of ABZ with the (+)-ABZSO being the predominant enantiomer in blood. Commencing with 2 ml of plasma, enantiomers present at >1 microg/ml could be detected only, a limitation which is based upon the strong absorbance of the chiral selector. (R)-DNBPG and ABZSO are negatively charged at pH 9.0-9.5, which prevents the application of a partial filling technique. The mobility of (R)-DNBPG is significantly larger compared to that of ABZSO. A migrating plug-plug approach based upon a plug of (R)-DNBPG migrating across the sample plug in an electroosmosis free environment obtained via a dynamic coating produced by spermine is shown to provide chiral resolution but not increased sensitivity.
authors.affiliation: Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland. wolfgang.thormann@ikp.unibe.ch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
authors.forename: Francine
authors.initials: F
authors.lastname: Prost
authors.forename: Andrea
authors.initials: A
authors.lastname: Procházková
mesh_terms: D015766:Albendazole / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry; D000871:Anthelmintics / Q000032:analysis* / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000379:methods; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006801:Humans; D009579:Nitrobenzoates / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000871:Anthelmintics; D009579:Nitrobenzoates; C051871:N-(3,5-dinitrobenzoyl)phenylglycine; D015766:Albendazole; C027186:albendazole sulfoxide; D005998:Glycine