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Stereoselectivity of the 4‐hydroxylation of debrisoquine in man, detected by gas chromatography/mass spectrometry 1
Author(s) -
Meese C. O.,
Fischer C.,
Eichelbaum M.
Publication year - 1988
Publication title -
biomedical and environmental mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0887-6134
DOI - 10.1002/bms.1200150202
Subject(s) - debrisoquine , hydroxylation , stereoselectivity , gas chromatography , chromatography , chemistry , gas chromatography–mass spectrometry , mass spectrometry , organic chemistry , biochemistry , metabolism , cyp2d6 , catalysis , cytochrome p450 , enzyme
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 ⩾90%).