Advertisement

Metabolite Methodology: The State-of-Play

Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 12)

Abstract

Examples of metabolite isolation or determination, partly from this book, are collated and annotated. Useful tools include TLC, GC and, increasingly, HPLC - notably RP-HPLC, though ordinary silica sometimes works better. Ionic additives may, empirically, improve the peak pattern; this may be poor for a conjugate and its parent compound in a single isocratic run. Immunoassay may be influenced by cross-reactivity of metabolites if not pre-separated. Sample preparation is briefly dealt with, as are interferences, losses and artefacts associated with the biological matrix, with solvents, or with the analyte (e.g. ‘OH-CPZ’ is adsorption-prone). For an especially difficult analyte, ‘SCMC’, the approach entailed phenylthiohydantoin formation. Conjugate types are listed, and hydrolysis is touched on.

Keywords

Parent Compound Drug Metabolite Mercapturic Acid Solid Agent Amyl Alcohol 
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. 1.
    Martin, L.E. & Reid, E. (1981)Progr. Drug Metab. 6, 197–248, [Bridges, J.W. & Chasseaud, L.F., eds.; Wiley, Chichester].Google Scholar
  2. 2.
    Chinn, D.M., Jennison, T.A., Crouch, D.J., Peat, M.A. & Thatcher, G.W. (1980)Clin. Chem. 26, 1201–1204.Google Scholar
  3. 3.
    Curry, S.H. & Brown, E.A. (1981)IRCS Med. Sci. 3, 170–171.Google Scholar
  4. 4.
    Caccia, S., Ballabio, M., Fanelli, R., Guiso, G. & Zanini, M.G. (1981)J. Chromatog. 210, 311–318.CrossRefGoogle Scholar
  5. 5.
    Astier, A., Maury, M. & Barbozet, J. (1979)Chromatog. 164, 235–240.CrossRefGoogle Scholar
  6. 6.
    Sawchuk, R.J. & Cartier, L.L. (1980)Clin. Chem, 22. 26, 835–839.Google Scholar
  7. 7.
    Horning, M.G., Gregory, P., Nowlin, J., Stafford, K., Lertrataitangkoon, K., Butler, C., Stillwell, W.G. & Hill, R.M. (1974)Clin. Chem. 20, 282–287Google Scholar
  8. 8.
    Henderson, G.L., Weinberg, J.A., Hargreaves, W.A., Lau, D.H.M., Tyler, J. & Baker, B. (1977)J. Anal. Toxicol. 2, 1–9.Google Scholar
  9. 9.
    Buhs, R.P., et al. (1974)J. Chromatog. 99, 609–618.CrossRefGoogle Scholar
  10. 10.
    Larsen, N.E. & Marinelli, K. (1978)J. Chromatog. 156, 335–339.CrossRefGoogle Scholar
  11. 11.
    Benvenuto, J.A., Stewart, D.J., Benjamin, R.S., Smith, R.G. & Loo, T.L. (1981)J. Chromatog. 222, 518–522.CrossRefGoogle Scholar
  12. 12.
    Tidd, D.M. & Dedhar, S. (1978)J. Chromatog. 145, 237–246.CrossRefGoogle Scholar
  13. 13.
    Sternson, L.A., Meitzer, N. & Shih, F.M.H. (1981)Anal. Lett. 148, 583–600.CrossRefGoogle Scholar
  14. 14.
    Guinebault, P.R., Broquaire, M., Sanjuan, M., Rovei, V. & Braithwaite, R.A. (1981)J. Chromatog. 223, 103–110.CrossRefGoogle Scholar
  15. 15.
    Muir, K.T., Jonkman, J.H.G., Tang, D.-S., Kunitani, M. & Riegelman, S. (1980)J. Chromatog. 221, 85–95CrossRefGoogle Scholar
  16. 16.
    Eriksson, B.-M., Tekenbergs, L., Magnusson, J.-0. & Molin, L. (1981)J. Chromatog. 223, 401–408.CrossRefGoogle Scholar
  17. 17.
    Eichhorst, O. & Hinderling, P.H. (1981)J. Chromatog. 224, 67–93.CrossRefGoogle Scholar
  18. 18.
    Ketelaars, H.J.C. & Peters, J.G.P. (1981)J. Chromatog. 224, 144–148.CrossRefGoogle Scholar
  19. 19.
    Veenendaal, J.R. & Meffin, P.J. (1981)J. Chromatog. 223, 147–154.CrossRefGoogle Scholar
  20. 20.
    Lewis, C.J. & Vose, C.W. (1981)Anal. Proc. 18, 253–255.Google Scholar
  21. 21.
    Neurath, G.B. & Ambrosius, D. (1979)J. Chromatog. 163, 230–235.CrossRefGoogle Scholar
  22. 22.
    Shackleton, C.H.L. (1981)Clin. Chem. 27, 509–511.Google Scholar
  23. 23.
    Dixon, P.F., Lukha, P. & Scott, N.R. (1979)Proc. Anal. Div. Chem. Soc. [now Anal. Proc.] 17, 302–305.Google Scholar
  24. 24.
    Lax, P.M. King, G.S., Pettit, B.R. & Sandler, M. (1979)Clin. Chem. Acta36, 269–272.CrossRefGoogle Scholar
  25. 25.
    Falkowski, A.J. & Wei, R. (1981)Anal. Biochem. 115, 311–317.CrossRefGoogle Scholar
  26. 26.
    Brüsewitz, G., Cameron, B.D., Chasseaud, L.F., Görler, K., Hawkins, D.R., Koch, H. & Mennicke, W.H. (1977)Biochem. J. 162, 99–107.Google Scholar
  27. 27.
    Wong, Z.A. & Hsieh, D.P.H. (1978)Science200, 325–327.CrossRefGoogle Scholar
  28. 28.
    Smith, C.L. & Thorgeirsson, S.S. (1981)Anal. Biochem. 113, 62–67.CrossRefGoogle Scholar
  29. 29.
    Krahn, M.M., Schnell, J.V. Uyeda, M.Y. & MacLeod, W.D. (1981)Anal. Biochem. 113, 27–33.CrossRefGoogle Scholar
  30. 30.
    Neal, R.A. (1967)Biochem. J. 103, 183–186.Google Scholar
  31. 31.
    Renwick, A.G. & Williams, R.T. (1972)Biochem. J. 229, 857–868.Google Scholar
  32. 32.
    Hirtz, J., ed. (1974) Fate of Drugs in the Organism, Vol. 1, Dekker, New York, 393 pp.; also subsequent volumes.Google Scholar
  33. 33.
    Stevenson, D. & Reid, E. (1981)Anal. Lett. 148, 1785–1805 [not 741–761 - a mutilated version that needs deletion + cross-ref. in Library copies, please; the topic is CPZ & metabolites].Google Scholar
  34. 34.
    Reid, E. (1976)Analyst101, 1–18.CrossRefGoogle Scholar
  35. 35.
    Riedmann, M. (1973)Xenobiotica3, 411–434CrossRefGoogle Scholar
  36. 36.
    Scoggins, B.A., Maguire, K.P. & Burrows, G.D. (198O) Clin. Chem. 26, 5–17.Google Scholar
  37. 37.
    Midha, K.K., Cooper, J.K. & Hubbard, J.W. (1980)Comm. Psychopharmacol. 1, 107–114.Google Scholar
  38. 37a.
    Anton, A.A. & Sayre, D.F. (1972) in The Thyroid and Biogenic Amines (Rail, J.E. & Kopin, I.J., eds.) , North Holland, Amsterdam, pp. 398–436.Google Scholar
  39. 38.
    Midha, K.K., Mackonka, C., Cooper, J.K., Hubbard, J.W. & Yeung, P.K.F. (1981)Br. J. Clin. Pharmacol. 1, 85–88.Google Scholar
  40. 39.
    Moffat, A.C. (1978)Proc. Anal. Div. Chem. Soc. 15, 237–239.CrossRefGoogle Scholar
  41. 40.
    Riceberg, L.J. & Van Vunakis, H. (1975) Biochem. Pharmacol. 24, 259–265.Google Scholar
  42. 41.
    Poklis, A. (1981)J. Anal. Toxicol. 5, 174–176.Google Scholar
  43. 42.
    Aldwin, L. & Kabakoff, D.S. (1981)Clin. Chem. 27, 770–771.Google Scholar
  44. 43.
    Mclntyre, I.M., Norman, T.R. & Burrows, G.D. (1981)Clin. Chem. 27, 203–204.Google Scholar
  45. 44.
    Jones, J.C., Carter, G.D. & Macgregor, G.A. (1981)Ann. Clin. Biochem. 18, 54–59.Google Scholar
  46. 45.
    Spindel, E., Pettibone, D., Fisher, L., Fernstrom, J. & Wurtman, R. (1981)J. Chromatog. 222, 381–387.CrossRefGoogle Scholar
  47. 46.
    Christofides, J.A. & Fry, D.E. (1980)Clin. Chem. 26, 499–501.Google Scholar
  48. 47.
    Knox, J.H., ed. ( 1978 [year unlisted]) High-Performance Liquid Chromatography, Edinburgh University Press, Edinburgh, 205 ppGoogle Scholar
  49. 48.
    Snyder, L.R. & Kirkland, J.J. (1979) Introduction to Modern Liquid Chromatography, 2nd edn., Wiley, New York.Google Scholar
  50. 49.
    Stafford, B.E., Kabra, P.M. & Marton, L. J. (1980)Clin. Chem. 26, 1366.Google Scholar
  51. 50.
    Wester, R., Noonan, P., Markos, C., Bible, R., Aksamit, W. & Hribar, O. (1981)J. Chromatog. 209, 463–466.CrossRefGoogle Scholar
  52. 51.
    Hansen, S.H. & Nordholm, L. (1981)J. Chromatog. 204, 97–101.CrossRefGoogle Scholar
  53. 52.
    Patel, R.B. & Welling, P.G. (1981)Clin. Chem. 27, 1780–1781.Google Scholar
  54. 53.
    Uehleke, H. & Brinkschulte-Freitas, M. (1978)Arch. Pharmacol. 302, 11–18.CrossRefGoogle Scholar
  55. 54.
    Reid, E., McDonald, T. & Burton, J.S. (1981)Anal. Lett. 148, 615–627.CrossRefGoogle Scholar
  56. 55.
    Trefz, F.K., Byrd, D.J., Blaskovics, M.E., Kochen, W. & Lutz, P. (1976)Clin. Chem. Acta73, 431–438.CrossRefGoogle Scholar
  57. 56.
    Bailey, J.L. (1967) Techniques in Protein Chemistry, 2nd edn., Elsevier, Amsterdam, 406 pp.Google Scholar
  58. 57.
    Friedman, M. (1973) The Chemistry and Biochemistry of the Sulphydryl Group in Amino acids, Pergamon, Oxford, 485 pp.Google Scholar
  59. 58.
    Kim, B.K. & Koda, R.J. (1977)J. Pharm. Sci. 66, 1632–1634.CrossRefGoogle Scholar
  60. 59.
    Blackburn, S. (1970) Protein Sequence Determination, Dekker, New York.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • E. Reid
    • 1
  1. 1.Wolfson Bioanalytical Unit, Robens Institute of Industrial & Environmental Health & SafetyUniversity of SurreyGuildfordUK

Personalised recommendations