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)

Xenobiotica

Volumn 26, Issue 2, 1996, Pages 189-199

  Shockcor, J P ^a   Wurm, R M ^a   Frick, L W ^a   Sanderson, P N ^b   Farrant, R D ^b   Sweatman, B C ^b   Lindon, J C ^b  

^a GLAXOSMITHKLINE   (United States)

^b WELLCOME RESEARCH LABORATORIES   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS;

DRUG METABOLITE; EMTRICITABINE; NUCLEOSIDE ANALOG;

ARTICLE; CLINICAL TRIAL; DRUG IDENTIFICATION; DRUG METABOLISM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; NUCLEAR MAGNETIC RESONANCE; ORAL DRUG ADMINISTRATION; URINE;

ANTIVIRAL AGENTS; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; GLUCURONATES; HIV; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; SPECTROPHOTOMETRY, ULTRAVIOLET; STEREOISOMERISM; SULFOXIDES; ZALCITABINE;

EID: 0029976111     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.3109/00498259609046699     Document Type: Article

References (20)

1. BAX, A., and DAVIS, D. G., 1985, MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy. Journal of Magnetic Resonance, 65, 355-360.
2. BAX, A., and SUBRAMANIAN, S., 1986, Sensitivity-enhanced two-dimensional heteronuclear shift correlation NMR spectroscopy. Journal of Magnetic Resonance, 67, 565-569.
3. DROBNY, D., PINES, A., SINTON, S., WEITEKAMP, D. P., and WEMMER, D., 1979, Fourier transform multiple quantum nuclear magnetic resonance. Journal of the Chemical Society, Faraday Division Symposia, 13, 49-55.
4. EMSLEY, J. W., PHILLIPS, L., and WRAY, V., 1976, Fluorine coupling constants, Progress in Nuclear Magnetic Resonance Spectroscopy, 10, 83-752.
5. FARRANT, R. D., SALMAN, S. R., LINDON, J. C., CUPID, B. C., and NICHOLSON, J. K., 1993, Deuterium NMR spectroscopy of biofluids for the identification of drug metabolites: application to N,N-dimethylformamide. Journal of Pharmaceutical and Biomedical Analysis, 11, 687-692.
6. FRICK, L. W., ST. JOHN, L., TAYLOR, L. C., PAINTER, G. R., FURMAN, P. A., LIOTTA, D. C., FURFINE, E., and NELSON, D. J., 1993, Pharmacokinetics, oral bioavailability and metabolic disposition in rats of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine (BW524W91), a nucleoside analogue active against human immunodeficiency virus and hepatitis B virus. Antimicrobial Agents and Chemotherapy, 37, 2285-2292.
7. GARBOW, J. R., WETTEKAMP, D, P., and PINES, A., 1982, Bilinear rotation decoupling of homonuclear scalar interactions. Chemical Physics Letters, 93, 504-509.
8. JOHNSON, S., MORGAN, E. D., WILSON, I. D., SPHAUL, M., and HOFMANN, M., 1994, Photo-isomerization of azadirachtin studied by high performance liquid chromatoyraphy coupled to high field proton NMR spectroscopy. Journal of the Chemical Society Perkin Transactions 1, 1499-1502.
9. LINDON, J. C., FARRANT, R. D., SANDERSON, P. N., DOYLE, P. M., GOUGH, S., SPRAUL, M., HOFMANN, M., and NICHOLSON, J. K., 1995b, Separation and characterisation of components of peptide libraries using on-flow coupled HPLC-NMR spectroscopy. Magnetic Resonance in Chemistry, 33, 857-863.
10. LINDON, J. C., NICHOLSON, J. K., and WILSON, I. D., 1995a, The development and application of coupled HPLC-NMR spectroscopy. Advances in Chromatography, 63, 315-382.
11. ROBERTS, J. K., and SMITH, R. J., 1994, Use of liquid chromatography-nuclear magnetic resonance spectroscopy for the identification of impurities in drug substances. Journal of Chromatography A, 677, 385-389.
12. SHINAZI, R. F., MCMILLAN, A., CANNON, D., MATHIS, R., LLOYD, R. M., PECK, A., SOMMADOSSI, J.-P., ST. CLAIR, M., WILSON, J., FURMAN, P. A., PAINTER, G. R., CHOI, W.-B., and LIOTTA, D. C., 1992, Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Antimicrobial Agents and Chemotherapy, 36, 2423-2431.
13. SIDELMANN, U. G., GAVAGHAN, C., CARLESS, H. A. J., FARRANT, R. D., LINDON, J. C., WILSON, I. D., and NICHOLSON, J. K., 1995a, Identification of the positional isomers of 2-fluorobenzoic acid 1-O-acyl-glucuronide by directly coupled HPLC-NMR. Analytical Chemistry, 67, 3401-3404.
14. 1H HPLC-NMR analysis of mixtures of isomeric ester glucuronide conjugates of trifluoromethylbenzoic acids. Journal of Chromatography (in press).
15. SPRAUL, M., HOFMANN, M., DVORTSAK, P., NICHOLSON, J. K., and WILSON, I. D., 1993b, High-performance liquid chromatography coupled to high-field proton nuclear magnetic resonance spectroscopy: application to the urinary metabolites of ibuprofen. Analytical Chemistry, 65, 327-330.
16. 1H-NMR spectroscopy for drug metabolite detection and characterisation: the identification of paracetamol metabolites in urine and bile. NMR in Biomedicine, 7, 295-303.
17. 1H-NMR spectroscopy to investigate the human urinary excretion of flurbiprofen metabolites. Journal of Pharmaceutical and Biomedical Analysis, 11, 1009-1015.
18. STATES, D. J., HABERKORN, R. H., and RUBEN, D. J., 1982, A two-dimensional nuclear Overhauser experiment with pure absorption phase in four quadrants. Journal of Magnetic Resonance, 48, 286-292.
19. 13C HPLC-NMR spectroscopy. Journal of Magnetic Resonance Analysis, 1, 9-12.
20. WILSON, I. D., NICHOLSON, J. K., HOFMANN, M., SPRAUL, M., and LINDON, J. C., 1993, Investigation of the human metabolism of antipyrine using coupled liquid chromatography and NMR spectroscopy of urine. Journal of Chromatography, 617, 324-328.