HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY STUDY OF STEREOSPECIFIC MICROSOMAL-ENZYMES CATALYZING THE REDUCTION OF A POTENTIAL CYTOSTATIC DRUG, ORACIN - INTERSPECIES COMPARISON

Citation
V. Wsol et al., HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY STUDY OF STEREOSPECIFIC MICROSOMAL-ENZYMES CATALYZING THE REDUCTION OF A POTENTIAL CYTOSTATIC DRUG, ORACIN - INTERSPECIES COMPARISON, Journal of chromatography, 797(1-2), 1998, pp. 197-201
Citations number
9
Categorie Soggetti
Chemistry Analytical","Biochemical Research Methods
Journal title
Volume
797
Issue
1-2
Year of publication
1998
Pages
197 - 201
Database
ISI
SICI code
Abstract
One of the main metabolites of oracin (I) -dioxo-5,6-dihydro-11H-inden o[1,2-c]isoquinoline}, a potential cytostatic drug, is 11-dihydrooraci n (II) ydroxy-5,6-dihydro-11H-indeno[1,2-c]isoquinoline}, a metabolite formed by the reduction of oracin's pro-chiral centre on C 11. This m etabolite has been found in all laboratory species in vitro and in viv o and it constitutes the main metabolite in man. The stereospecificity of reducing enzymes participating in the oracin biotransformation pat hway was investigated using microsomal preparations from standard labo ratory animals. Enzyme stereospecificity has been defined as preferent ial formation by the enzyme of the (+) or (-) stereoisomer of II. Sign ificant interspecies differences were observed in the stereospecificit y of the respective biotransformation enzymes. HPLC quantitative deter minations of both enantiomers were performed using a Chiralcel OD-R co lumn as chiral stationary phase with excellent resolution and stabilit y. (C) 1998 Elsevier Science B.V.