Evidence for a new and major metabolic pathway of clenbuterol involving in vivo formation of an N-hydroxyarylamine

Chemical Research in Toxicology

Volumn 10, Issue 2, 1997, Pages 197-204

  Zalko, Daniel ^a   Debrauwer, Laurent ^a   Bories, Georges ^a   Tulliez, Jacques ^a  

^a CEMAGREF   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CLENBUTEROL;

ARTICLE; DRUG EXCRETION; DRUG METABOLISM; DRUG OXIDATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ISOTOPE LABELING; LIVER MICROSOME METABOLISM;

ADMINISTRATION, ORAL; ANIMALS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CLENBUTEROL; DRUG STABILITY; FERRICYANIDES; FERROUS COMPOUNDS; HYDROXYLAMINES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; MICROSOMES, LIVER; ORGANOMETALLIC COMPOUNDS; RATS; RATS, WISTAR;

ANIMALIA; BOS TAURUS; BOVINAE;

EID: 0031049552     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx960143s     Document Type: Article

References (37)

1. Martinez-Navarro, J. F. (1990) Food poisoning related to consumption of illicit β-agonist in liver. Lancet 336, 1311.
2. Pulce, C., Lamaison, D., Keck, G., Bostvironnois, C., Nicolas, J., Descotes, J., Mora, M., and Colmant, A. (1991) Intoxication alimentaire collective due à la présence de résidus de clenbuterol dans du foie de veau. Bull. épidémiol. hebd. 5, 17-18.
3. Meyer, H. H. D., and Rinke, L. M. (1991) The pharmacokinetics and residues of clenbuterol in veal calves. J. Anim. Sci. 69, 4538-4544.
4. Kopitar, Z., and Zimmer, A. (1976) Pharmakokinetik und metabolitenmuster von clenbuterol bei der rat (Pharmacokinetics and metabolite pattern of clenbuterol in the rat). Arzneim.-Forsch. 26, 1435-1441.
5. Tanabe, H., Yamamoto, M., Kageyama, H., Kubo, J., and Naruchi, T. (1984) Metabolic fate of Clenbuterol (NAB 365) I absorption, distribution and excretion in rats. Iyakuhin Kenkyu 15, 448-460.
6. Tanabe, H., Kageyama, H., Kubo, J., and Naruchi, T. (1984) Metabolic fate of Clenbuterol (NAB 365) III metabolism in rats and dogs. Iyakuhin Kenkyu. 15, 467-476.
7. Schmid, J., Prox, A., Zimmer, A., Keck, J., and Kaschke S. (1990) Biotransformation of Clenbuterol. Fresenius J. Anal. Chem. 337, 121.
8. Smith, M. R., and Gorrod, J. W. (1978) The microsomal N-oxidation of some primary aromatic amines. In Biological oxidation of nitrogen (Gorrod, J. W., Ed.) pp 65-70, Elsevier/North-Holland biomedical press, Amsterdam.
9. Uetrecht, J. P. (1992) The role of leukocyte-generated reactive metabolites in the pathogenesis of idiosyncratic drug reactions. Drug Metab. Rev. 24, 299-366.
10. Uetrecht, J. P., Sweetman, B. J., Woosley, R. L., and Oates, J. A. (1984) Metabolism of procainamide to a hydroxylamine by rat and human hepatic microsomes. Drug Metab. Dispos. 12, 77-81.
11. 3H-clenbuterol in the rat and bovine. Proceedings of the Euroresidue III conference, Veldhoven, The Netherlands, 6-8 May, 993-997.
12. Corbett, M. D., and Chipko, B. R. (1978) Synthesis and antibiotic properties of chloramphenicol reduction products. Antimicrob. Agents Chemother. 13, 193-198.
13. Perdu-Durand, E. F., and Tulliez, J. E. (1985) Hydrocarbon hydroxylation system in liver microsomes from four animal species. Food Chem. Toxicol. 23, 363-366.
14. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265-275.
15. Feigl, F. (1975) In Spot tests in organic analysis, Elsevier, Amsterdam.
16. Debrauwer, L., and Bories, G. (1992) Electrospray ionization mass spectrometry of some β-agonists. Rapid Commun. Mass Spectrom. 6, 382-387.
17. Debrauwer, L., and Bories, G. (1993) Determination of clenbuterol residues by liquid chromatography-electrospray mass spectrometry. Anal. Chim. Acta 275, 231-239.
18. Doerge, D. R, Bajic, S., and Lowes, S. (1993) Analysis of clenbuterol in human plasma using liquid chromatography/atmospheric-pressure chemical-ionization mass spectrometry. Rapid Commun. Mass Spectrom. 7, 462-464.
19. Coutts, R. T., and Mukherjee, G. (1970) Identification of the aromatic hydroxyl-amine group by mass spectrometry. Org. Mass Spectrom. 3, 63-65.
20. Saito, K., Yamazoe, Y., Kamataki, T., and Kato, R. (1985) Fast-atom bombardment and electron-impact mass spectrometry of N-hydroxyarylamines, active intermediates of mutagenic aromatic amines. Xenobiotica 15, 327-332.
21. Emmons, W. D. (1957) The oxidation of amines with peracetic acid. J. Am. Chem. Soc. 79, 5528-5530.
22. Sternson, L. A., and Dewitte, W. J. (1978) Methods for the analysis of arylamines and their N-and C-hydroxylated metabolites. In Biological oxidation of nitrogen. (Gorrod, J. W., Ed.) pp 257-262, Elsevier/North-Holland biomedical press, Amsterdam.
23. Patterson, L. H., Damani, L. A., Smith, M. R., and Gorrod, J. W. (1978) Use of chromatographic techniques for the detection and quantitation of N-oxygenated metabolites. In Biological oxidation of nitrogen (Gorrod, J. W, ed.) pp 213-230, Elsevier/North-Holland biomedical press, Amsterdam.
24. Testa, B., and Jenner, P. (1978) Novel drug metabolites produced by functionalization reactions: chemistry and toxicology. Drug Metab. Rev. 7, 325-369.
25. Gorrod, J. W. (1973) Differentiation of various types of biological oxidation of nitrogen in organic compounds. Chem. Biol. Interact. 7, 289-303.
26. Lindeke, B. (1982) The non-and postenzymatic chemistry of N-oxygenated molecules. Drug Metab. Rev. 13, 71-121.
27. Beckett, A. H., Purkaystha, A. R., and Morgan, P. H. (1977) Oxidation of aliphatic hydroxylamines in aqueous solutions. J. Pharm. Pharmacol. 29, 15-21.
28. 14C]practolol metabolite(s) to mammalian liver microsomes. J. Pharmacol. Exp. Ther. 219, 207-212.
29. Uetrecht, J. P. (1984) Reactivity and possible significance of hydroxylamine and nitroso metabolites of procainamide. J. Pharmacol. Exp. Ther. 232, 207-212.
30. Sabbioni, G. (1994) Hemoglobin binding of arylamines and nitroarenes: molecular dosimetry and quantative structure-activity relationships. Environ. Health Perspect. (suppl. 6), 61-67.
31. Mallett, A. K. and Rowland, I. R. (1985) Dietary control of bacterial nitro-group metabolism, in Biological oxidation of nitrogen in organic molecules: chemistry, toxicology and pharmacology (Gorrod J. W., and Damani L. A., Eds.) pp 154-159, Ellis Horwood series in health sciences, Ellis Horwood Ltd., Chichester, England.
32. Chadwick, R. W., George, S. E., and Claxton, L. D. (1992) Role of the gastrointestinal mucosa and microflora in the bioactivation of dietary and environmental mutagens or carcinogens. Drug Metab. Rev. 24, 425-492.
33. Guest, D., Schnell, S. R., Rickert, D. E., and Dent, J. G. (1982) Metabolism of 2,4-dinitrotoluene by intestinal microorganisms from rat, mouse and man. Toxicol. Appl. Pharmacol. 64, 160-168.
34. Brambilla, G., Civitareale, C., and Pierdominici, E. (1994) Synovial fluid as a matrix of selection in the detection of beta-adrenergic agonist drugs in carcasses and fresh meat. Analyst 119, 2591-2593.
35. Leyssens, L., Van Der Greef, J., Penxten, H., Czech, J., Noben, J. P., Adriaensens, P., Gelan, J., and Raus, J. (1993) Structure elucidation of unknown clenbuterol analogues detected in illegal preparations for animal use. Proceedings of the Euroresidue II conference, Veldhoven, The Netherlands, 3-5 May, 444-449.
36. Saltron, F., Berthoz, Y., Rues, R., Auguin, N., and Belhade, L. (1996) Structure elucidation of clenbuterol-and mabuterol-like compounds in complex matrices using silylated and n-butylboronate derivatives by gas chromatography/electron impact and chemical ionization mass spectrometry. J. Mass Spectrom. 31, 810-818.
37. Barrow, A., Camp, S. J., Dayal, S., Jenner, W. N., Lashmar, D., Oxford, J. M., Palmer, E., Scully, N. L., Curtis, G. C., Hughes, H. M., and Park, G. W. (1995) Kinetics and disposition of picumeterol in animals. Xenobiotica 25, 993-1007.