title: Stereoselectivity of the 4-hydroxylation of debrisoquine in man, detected by gas chromatography/mass spectrometry.
abstract: A stable isotope assay for the quantification of debrisoquine (1) and its major urinary metabolite 4-hydroxydebrisoquine (2) is described. The method consists of extractive derivatization of 1 and 2 by use of 1,3-diketones, chiral derivatization of the 4-hydroxy group of 2, and gas chromatography/negative ion chemical ionization mass spectrometry in the presence of deuterated analogues of 1 and 2. In comparison with synthetic R-(-)-2 and S-(+)-2 it is shown that in vivo benzylic 4-hydroxylation of 1 is highly stereoselective, leading predominantly to S-(+)-4-hydroxydebrisoquine (enantiomeric excess greater than or equal to 90%).
authors.affiliation: Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, FRG.
authors.forename: C O
authors.initials: CO
authors.lastname: Meese
authors.forename: C
authors.initials: C
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Eichelbaum
mesh_terms: D001152:Arsenicals / Q000032:analysis*; D001711:Biotransformation; D002794:Choline / Q000031:analogs & derivatives* / Q000032:analysis; D003647:Debrisoquin / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000652:urine*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D001152:Arsenicals; D007202:Indicators and Reagents; D007546:Isoquinolines; C035463:acetylarsenocholine; C012359:4-hydroxydebrisoquin; D002794:Choline; D003647:Debrisoquin