Advertisement

The use of deuterium labelling in mechanistic studies of metabolic activation

  • M. Jarman
  • P. B. Farmer
  • A. B. Foster
  • P. J. Cox

Abstract

Stable isotopes have been used, in conjunction with mass spectrometry, in a variety of biomedical applications. Of these, the most widely exemplified has been the quantification of drugs and their metabolites in biological fluids (e.g. blood, urine), by mass spectrometry—stable-isotope dilution using isotopically labelled analogues as the reference standards. This technique has been extensively reviewed (Jenden and Cho, 1973; Horning et al., 1973; Lawson and Draffan, 1975) and need not be detailed here except to note that, for reasons of cost and ease of synthesis, deuterium has been the most frequently employed isotope, although, in principle, any other stable isotope (e.g. 13C, 15N, 18O, 34S) can be used.

Keywords

Stable Isotope Isotope Effect Metabolic Switching Deuterium Labelling Intermediary Metabolite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdel-Monem, M. M. (1975). J. Med. Chem., 18, 427CrossRefGoogle Scholar
  2. Bigeleisen, J. (1949). Science, N.Y. 110, 14CrossRefGoogle Scholar
  3. Colvin, M., Padgett, C. A. and Fenselau, C. (1973). Cancer Res., 33, 915Google Scholar
  4. Connors, T. A., Cox, P. J., Farmer, P. B., Foster, A. B. and Jarman, M. (1974a). Biochem. Pharmacol., 23, 115CrossRefGoogle Scholar
  5. Connors, T. A., Cox, P. J., Farmer, P. B., Foster, A. B., Jarman, M. and MacLeod, J. K. (1974b). Biomed. Mass Spectrom., 1, 130CrossRefGoogle Scholar
  6. Cox, P. J., Farmer, P. B., Foster, A. B., Gilbey, E. D. and Jarman, M. (1976a). Cancer Treatment Rep., 60, 483Google Scholar
  7. Cox, P. J., Farmer, P. B., Jarman, M., Jones, M., Stec, W. J. and Kinas, R. (1976b). Biochem. Pharmacol., 25, 993CrossRefGoogle Scholar
  8. Dagne, E., Gruenke, L. and Castagnoli, N. (1974). J. Med. Chem., 17, 1330 Daly, J., Jerina, D. and Witkop, B. (1968). Arch. Biochem. Biophys., 128, 517Google Scholar
  9. Ehrsson, H. (1976). J. Pharm. Pharmacol., 28, 662CrossRefGoogle Scholar
  10. Farmer, P. B., Foster, A. B. and Jarman, M. (1975). Biomed. Mass Spectrom., 2, 107CrossRefGoogle Scholar
  11. Foster, A. B., Jarman, M., Stevens, J. D., Thomas, P. and Westwood, J. H. (1974). Chem.-Biol. Interactions, 9, 327CrossRefGoogle Scholar
  12. Gal, J., Gruenke, L. D. and Castagnoli, N. (1975). J. Med. Chem., 18, 683CrossRefGoogle Scholar
  13. Horning, M. G., Nowlin, J., Lertratanangkoon, K., Stillwell, R. N., Stillwell, W. G. and Hill, R. M. (1973). Clin. Chem., 19, 845Google Scholar
  14. Jenden, D. J. and Cho, A. K. (1973). Ann. Rev. Pharmacol., 13, 371CrossRefGoogle Scholar
  15. Johnston, T. P., McCaleb, G. S. and Montgomery, J. A. (1975). J. Med. Chem., 18, 634CrossRefGoogle Scholar
  16. Kakis, F. J., Fetizon, M., Douchkine, N., Golfier, M., Mourgues, P. and Prange, T. (1974). J. Org. Chem., 39, 523CrossRefGoogle Scholar
  17. Kinas, R., Pankiewicz, K. and Stec, W. J. (1975). Bull. Acad. Pol. Sci. Ser. Sci. Chim., 23, 981Google Scholar
  18. Knapp, D. R., Gaffney, T. E. and McMahon, R. E. (1972a). Biochem. Pharmacol., 21, 425CrossRefGoogle Scholar
  19. Knapp, D. R., Gaffney, T. E., McMahon, R. E. and Kiplinger, G. (1972b). J. Pharmacol. Exp. Ther., 180, 784Google Scholar
  20. Lawson, A. M. and Draffan, G. H. (1975). Prog. Med. Chem., 12, 1CrossRefGoogle Scholar
  21. Lijinsky, W., Loo, J. and Ross, A. E. (1968). Nature, 218, 1174CrossRefGoogle Scholar
  22. McGraw, N. P., Caliery, P. S. and Castagnoli, N. (1976). J. Med. Chem. (in press)Google Scholar
  23. May, H. E., Boose, R. and Reed, D. J. (1974). Biochem. Biophys. Res. Commun., 57, 426CrossRefGoogle Scholar
  24. Mitoma, C., Yasuda, D. M., Tagg, J. and Tanabe, M. (1967). Biochim. Biophys. Acta, 136, 566CrossRefGoogle Scholar
  25. Selander, H. G., Daly, J. and Jerina, D. (1975). Arch. Biochem. Biophys., 168, 309CrossRefGoogle Scholar
  26. Struck, R. F., Kirk, M. C., Mellett, L. B., El Dareer, S. and Hill, D. L. (1971). Molec. Pharmacol., 7, 519Google Scholar
  27. Tanaka, N. and Thornton, E. R. (1976). J. Am. Chem. Soc., 98, 1617CrossRefGoogle Scholar
  28. Takamizawa, A., Matsumoto, S., Iwata, T., Tochino, Y., Katagiri, K., Yamaguchi, K. and Shiratori, O. (1975). J. Med. Chem., 18, 376CrossRefGoogle Scholar
  29. Tomaszewski, J. E., Jerina, D. M. and Daly, J. W. (1975). Biochemistry, 14, 2024.CrossRefGoogle Scholar

Copyright information

© The Contributors 1978

Authors and Affiliations

  • M. Jarman
    • 1
  • P. B. Farmer
    • 1
  • A. B. Foster
    • 1
  • P. J. Cox
    • 1
  1. 1.Chester Beatty Research Institute, Institute of Cancer ResearchRoyal Cancer HospitalLondonUK

Personalised recommendations