Stereoselectivity of the 4-hydroxylation of debrisoquine in man, detected by gas chromatography/mass spectrometry.
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%).
Meese
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Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, FRG.
Fischer
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Eichelbaum
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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
D001152:Arsenicals; D007202:Indicators and Reagents; D007546:Isoquinolines; C035463:acetylarsenocholine; C012359:4-hydroxydebrisoquin; D002794:Choline; D003647:Debrisoquin