19F NMR Studies of the Metabolism of Trifluoromethylaniline

  • K. E. Wade
  • J. Troke
  • C. M. Macdonald
  • I. D. Wilson
  • J. K. Nicholson
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 18 A)

Abstract

There is now much interest in the application of NMR techniques to determine the metabolic fate and disposition of foreign compounds [1–4] (& J.K. Nicholson in Vols. 16 & 17, this series — Ed.). For fluorinated compounds 19F NMR can be used with particular advantage due to its large chemical shift range giving good specificity, high sensitivity (83% of 1H) and the absence of endogenous fluorinated compounds in body fluids. In theory, drug recovery studies can be achieved by quantifying the spectra using a known concentration of a standard, thus obviating the need for expensive synthesis of radiolabelled compounds. To illustrate this, we have now investigated the metabolism and urinary excretion of TFMA* and its acetanilide. TLC and GC-MS studies [5] had shown that TFMA is metabolized to its oxanilic acid and a hydroxy metabolite which is probably glucuronidated (Fig. 1).

Keywords

Hydroxy Metabolite Excretion Profile Radiolabelled Compound Fresh Urine Sample Pharmaceutical Research Laboratory 
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.

Abbreviation

TFMA

4-trifluoromethylaniline

Fid

free induction decay

FT

Fourier transformation

MS

mass spectrometry

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References

  1. 1.
    Everett, J.R., Jennings, K. & Woodnutt, G. (1985) J. Pharm. Pharmacol. 37, 869–873.CrossRefGoogle Scholar
  2. 2.
    Tulip, K., Timbrell, J.A., Wilson, I.D., Troke, J. & Nicholson, J.K. (1986) Drug Metab. Disp. 14, 746–749.Google Scholar
  3. 3.
    Nicholson, J.K., Timbrell, J.A., Bales, J.R. & Sadler, P.J. (1985) Molec. Pharmacol. 27, 634–644.Google Scholar
  4. 4.
    Coleman, M.D. & Norton, R.S. (1986) Xenobiotica 16, 69–77.CrossRefGoogle Scholar
  5. 5.
    Wilson, I.D., Macdonald, C.M., Fromson, J.M., Troke, J.A. & Hillbeck, D. (1985) Biochem. Pharmacol. 34, 2025–2028.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • K. E. Wade
    • 1
  • J. Troke
    • 1
    • 2
  • C. M. Macdonald
    • 1
    • 2
  • I. D. Wilson
    • 1
    • 2
  • J. K. Nicholson
    • 1
  1. 1.Department of ChemistryBirkbeck College (University of London)LondonUK
  2. 2.Department of Drug MetabolismHoechst Pharmaceuticals Research LaboratoriesWalton Manor, Walton, Milton Keynes, BucksUK

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