Stereoselectivity of the 4-hydroxylation of debrisoquine in man, detected by gas chromatography/mass spectrometry1
- 15 January 1988
- journal article
- research article
- Published by Wiley in Journal of Mass Spectrometry
- Vol. 15 (2) , 63-66
- https://doi.org/10.1002/bms.1200150202
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 ⩾90%).This publication has 16 references indexed in Scilit:
- Absolute Configuration of 1,2,3,4-Tetrahydro-4-hydroxyisoquinolinesEuropean Journal of Organic Chemistry, 1987
- Synthesis of 1,1,3,3‐(2h4)‐4‐hydroxydebrisoquine sulphateJournal of Labelled Compounds and Radiopharmaceuticals, 1986
- The electron capture negative ion chemical ionization mass spectra of 2-(4′,6′-bistrifluoromethyl-2′-pyrimidinyl)-tetrahydroisoquinoline and 4-substituted analoguesJournal of Mass Spectrometry, 1982
- The metabolism of [14C]‐debrisoquine in man.British Journal of Clinical Pharmacology, 1979
- POLYMORPHIC HYDROXYLATION OF DEBRISOQUINE IN MANThe Lancet, 1977
- Determination of debrisoquin and its 4-hydroxy metabolite in plasma by gas chromatography/mass spectrometryAnalytical Chemistry, 1976
- Gas-liquid chromatographic electron capture determination of some monosubstituted guanido-containing drugsAnalytical Chemistry, 1975
- The Use of R-(+)-1-Phenylethylisocyanate in the Optical Analysis of Asymmetric Secondary Alcohols by Gas ChromatographyAnalytical Letters, 1970
- Use of (-)-menthyl chloroformate in the optical analysis of asymmetric amino and hydroxyl compounds by gas chromatographyThe Journal of Organic Chemistry, 1968
- 1,2,3,4-Tetrahydroisoquinoline Derivatives with Antihypertensive PropertiesJournal of Medicinal Chemistry, 1965