title: Investigation of the stereoselective metabolism of the chiral H1-antihistaminic drug terfenadine by high-performance liquid chromatography.
abstract: The enantiomers of the racemic H1-antihistaminic drug terfenadine (1) have been resolved by fractional crystallization of the diastereomeric salts with optically active 2-chlorotartranilic acid. The enantiomeric excess of both terfenadine enantiomers was determined using an achiral and a chiral HPLC system after formation of diastereomers with S-(+)-naphthylethylisocyanate. To investigate the metabolism of terfenadine after oral administration, an achiral HPLC system, equipped with a conventional reversed-phase column, was used to quantify the main metabolite MDL 16.455 (2) in human serum and urine. The determination of the enantiomeric composition of 2 was achieved using an Ultron ES-OVM column as chiral stationary phase. Metabolite 2, extracted from human blood plasma, was found to be enriched in the R-enantiomer, but was excreted in urine as racemate. The results of a study including six volunteers are presented.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Münster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Terhechte
authors.forename: G
authors.initials: G
authors.lastname: Blaschke
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006801:Humans; D015203:Reproducibility of Results; D013237:Stereoisomerism; D016593:Terfenadine / Q000031:analogs & derivatives / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine
chemical_list: D016593:Terfenadine; C093230:fexofenadine