High-performance liquid chromatographic assay for the separation and characterization of metabolites of the potential cytostatic drug oracine |
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| Affiliation: | 1. Academy of Scientific and Innovative Research, New Delhi, India;2. Pharmaceutics and Pharmacokinetics Division, CSIR – Central Drug Research Institute, Lucknow, Uttar Pradesh, India;1. Univ. Lille, Inserm, CHU Lille, U1172 LilNCog - Lille Neuroscience & Cognition, Lille, France;2. Alzheimer &Tauopathies, LabEx DISTALZ, France;3. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Animal Facility, F-59000, Lille, France;1. Preclinical Pharmacokinetic Shared Resource, St. Jude Children''s Research Hospital, Memphis, TN, 38105, USA;2. Department of Chemical Biology and Therapeutics, St. Jude Children''s Research Hospital, Memphis, TN, 38105, USA;1. IDENIX an MSD Company, Cap Gamma, 1682 rue de la Valsière, 34189 Montpellier Cedex 4, France;2. Merck & Co., Inc., PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, USA;3. IDENIX Pharmaceuticals, 320 Bent Street - 4th Floor, Cambridge, MA 02139, USA;4. UMR 5247 CNRS-Université Montpellier-ENSCM, case courrier 1705, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France;1. LIWET, Department of Industrial Biological Sciences, Ghent University, Campus Kortrijk, Graaf Karel de Goedelaan 5, 8500 Kortrijk, Belgium;2. BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Coupure Links 653, B-9000 Gent, Belgium |
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| Abstract: | Oracine (I), a potential cytostatic drug, is enzymically converted to a number of metabolites whose formation has been studied in vitro and in vivo. The metabolites were separated by reversed-phase HPLC and characterized by UV spectra. Preparative TLC served for the isolation of the individual metabolites to allow their identification. Two metabolites were identified by Fourier transform NMR as 11-dihydrooracine (II) and a phenolic product (III). Two further metabolites (IV,V) were characterized. Some minor, presumably 11-dihydro metabolites and an 11-oxo metabolite produced in vitro and in vivo were revealed. |
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