title: Investigation of the in vitro biotransformation and simultaneous enantioselective separation of thalidomide and its neutral metabolites by capillary electrophoresis.
abstract: Reversed-phase liquid chromatography is a long established method for the analysis of drug metabolism. The current investigation demonstrates that micellar electrokinetic capillary chromatography can be an attractive alternative. Two methods were developed using sodium dodecyl sulfate and hexadecyltrimethylammonium bromide for the determination of possible hydroxylated metabolites of the former sedative drug thalidomide (Contergan) in order to study the in vitro metabolism of the drug by incubation with rat liver microsomes. The biotransformation was found to be stereoselective: S-(-)-thalidomide mainly formed 5-hydroxythalidomide, whereas R-(+)-thalidomide was preferentially transformed to two metabolites tentatively assigned to be diastereomers of 5'-hydroxythalidomide. Furthermore, the simultaneous enantioseparation of thalidomide and two of its possible hydroxylated metabolites was achieved using capillary electrophoresis with negatively charged carboxymethyl-beta-cyclodextrin. The dependencies of the selectivity of the enantioseparation on the concentration of the chiral additive and the pH of the run buffer were investigated.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weinz
authors.forename: G
authors.initials: G
authors.lastname: Blaschke
mesh_terms: D000818:Animals; D001711:Biotransformation; D002021:Buffers; D019075:Electrophoresis, Capillary / Q000379:methods* / Q000706:statistics & numerical data; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013792:Thalidomide / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*
chemical_list: D002021:Buffers; D013792:Thalidomide