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Hplc-nmr identification of the human urinary metabolites of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, a nucleoside analogue active against human immunodeficiency virus (HIV). 1996

J P Shockcor, and R M Wurm, and L W Frick, and P N Sanderson, and R D Farrant, and B C Sweatman, and J C Lindon
Wellcome Research Laboratories, Research Triangle Park, NC 27706, USA.

1. Human urine samples from a clinical trial of the anti-HIV compound (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-cyto sin e (BW524W91) have been analysed using 19F-nmr and 1H-hplc-nmr spectroscopy. 2. The identities and relative levels of the xenobiotic species in the urine have been determined by 470-MHz 19F-nmr spectroscopy and by directly coupled 600-MHz 1H-hplc-nmr in the stop-flow mode with confirmation of the metabolite identities being made by comparison with nmr spectra of synthetic standard compounds. 3. The principal urinary xenobiotic was the unchanged drug, but the glucuronide ether conjugate at the 5' position of BW524W91, one of the two diastereomeric sulphoxides and the deaminated metabolite were also characterized. 4. The detection limit of directly coupled hplc-600-MHz 1H-nmr spectroscopy was evaluated by measuring two-dimensional nmr spectra of the glucuronide conjugate of BW524W91 and shown to be approximately 1 microgram material for 1H-1H-TOCSY and 20 micrograms metabolite for 1H-13C-HMQC spectra for overnight (16 h) acquisition.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006678 HIV Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2. AIDS Virus,HTLV-III,Human Immunodeficiency Viruses,Human T-Cell Lymphotropic Virus Type III,Human T-Lymphotropic Virus Type III,LAV-HTLV-III,Lymphadenopathy-Associated Virus,Acquired Immune Deficiency Syndrome Virus,Acquired Immunodeficiency Syndrome Virus,Human Immunodeficiency Virus,Human T Cell Lymphotropic Virus Type III,Human T Lymphotropic Virus Type III,Human T-Cell Leukemia Virus Type III,Immunodeficiency Virus, Human,Immunodeficiency Viruses, Human,Virus, Human Immunodeficiency,Viruses, Human Immunodeficiency,AIDS Viruses,Human T Cell Leukemia Virus Type III,Lymphadenopathy Associated Virus,Lymphadenopathy-Associated Viruses,Virus, AIDS,Virus, Lymphadenopathy-Associated,Viruses, AIDS,Viruses, Lymphadenopathy-Associated
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068679 Emtricitabine A deoxycytidine analog and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B viruses. It is used to treat HIV INFECTIONS. Beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine,Coviracil,Emtriva,Beta L 2',3' dideoxy 5 fluoro 3' thiacytidine
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013056 Spectrophotometry, Ultraviolet Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Ultraviolet Spectrophotometry
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer

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