A trapping method for semi-quantitative assessment of reactive metabolite formation using 35S cysteine and 14C cyanide

Drug Metabolism and Pharmacokinetics

Volumn 24, Issue 3, 2009, Pages 245-254

  Inoue, Kazuko ^a   Shibata, Yoshihiro ^a   Takahashi, Hiroyuki ^a   Ohe, Tomoyuki ^a   Chiba, Masato ^a   Ishii, Yasuyuki ^a  

^a BANYU PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Analytical method; Bioactivation; Covalent binding; Reactive metabolites; Trapping assay

Indexed keywords

CARBON 14; CLOZAPINE; CYANIDE; CYSTEINE; DICLOFENAC; ELECTROPHILE; PULEGONE; SULFUR 35; TROGLITAZONE;

ACCURACY; ANALYTIC METHOD; ARTICLE; CHEMICAL ANALYSIS; CONTROLLED STUDY; COVALENT BOND; DRUG ACTIVATION; DRUG DETERMINATION; DRUG PROTEIN BINDING; FALSE NEGATIVE RESULT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; INTERMETHOD COMPARISON; ION TRAP MASS SPECTROMETRY; ISOTOPE LABELING; LIVER MICROSOME; METABOLIC ACTIVATION; METABOLITE; PROCESS OPTIMIZATION; PROTEIN BINDING; PROTEIN DETERMINATION; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; RADIOCHROMATOGRAPHY; TRAPPING ASSAY;

EID: 69949185975     PISSN: 13474367     EISSN: 18800920     Source Type: Journal    
DOI: 10.2133/dmpk.24.245     Document Type: Article

References (35)

1. Liebler, D. C. and Guengerich, F. P.: Elucidating mechanisms of drug-induced toxicity. Nat. Rev. Drug Disc., 4: 410-420 (2005).
2. Walgren, J. L., Mitchell, M. D. and Thompson, D. C.: Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit. Rev. Toxicol., 35: 325-361 (2005).
3. Baillie, T. A.: Future of toxicology-metabolic activation and drug design: Challenges and opportunities in chemical toxicology. Chem. Res. Toxicol., 19: 889-893 (2006).
4. Evans, D. C. and Baillie, T. A.: Minimizing the potential for metabolic activation as an integral part of drug design. Curr. Opin. Drug Dis. Develop., 8: 44-50 (2005).
5. Amacher, D. E.: Reactive intermediates and the pathogenesis of adverse drug reactions: The toxicology perspective. Curr. Drug Metab., 7: 219-229 (2006).
6. Doss, G. A. and Baillie, T. A.: Addressing metabolic activation as an integral component of drug design. Drug Metab. Rev., 38: 641-649 (2006).
7. Tang, W.: Drug metabolite profiling and elucidation of drug-induced hepatotoxicity. Expert Opin. Drug Metab. Toxicol., 3: 407-420 (2007).
8. Caldwell, G. W. and Yan, Z.: Screening for reactive intermediates and toxicity assessment in drug. Curr. Opin. Drug Dis. Develop., 9: 47-60 (2006).
9. Uetrecht, J.: Screening for the potential of a drug candidate to cause idiosyncratic drug reactions. Drug Dis. Today, 8: 832-837 (2003).
10. Day, S. H., White, R., Schulz-Utermoehl, T., Miller, R. and Beconi, M. G.: A semi-automated method for measuring the potential for protein covalent binding in drug discovery. J. Pharmacol. Toxicol. Methods, 52: 278-285 (2005).
11. Evans, D. C., Watt, A. P., Nicoll-Griffith, D. A. and Baillie, T. A.: Drug-Protein Adducts: An Industry Perspective on Minimizing the Potential for Drug Bioactivation in Drug Discovery and Development. Chem. Res. Toxicol., 17: 3-16 (2004).
12. Gan, J., Harper, T.W., Hsueh, M., Qu, Q. and Humphreys, W. G.: Dansyl glutathione as a trapping agent for the quantitative estimation and identification of reactive metabolites. Chem. Res. Toxicol., 18: 896-903 (2005).
13. Masubuchi, N., Makino, C. and Murayama, N.: Prediction of in vivo potential for metabolic activation of drugs into chemically reactive intermediates: Correlation of in vitro and in vivo generation of reactive intermediates and in vitro glutathione conjugate formation in rats and human. Chem. Res. Toxicol., 20: 455-464 (2007).
14. Liu, Z. C. and Uetrecht, J. P.: Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion that irreversibly binds to the cells. J. Pharmacol. Exp. Ther., 275: 1476-1483 (1995).
15. Boelsterli, U. A.: Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. Toxicol. Appl. Pharmacol., 192: 307-322 (2008).
16. Tettey, J. N., Maggs, J. L., Rapeport, W. G., Pirmohamed, M. and Park, B. K. Enzyme-induction dependent bioactivation of troglitazone and troglitazone quinone in vivo. Chem. Res. Toxicol., 14: 965-974 (2001).
17. He, K., Talaat, R. E., Pool, W. F., Reily, M. D., Reed, J. E., Bridges, A. J. and Woolf, T. F.: Metabolic activation of troglitazone: identification of a reactive metabolite and mechanisms involved. Drug Metab. Dispos., 32: 639-646 (2004).
18. Williams, D. P., Pirmohamed, M., Naisbitt, D. J., Maggs, J. L. and Park, B. K.: Neutrophil cytotoxicity of the chemically reactive metabolite(s) of clozapine: Possible role in agranulocytosis. J. Pharmacol. Exp. Ther., 283: 1375-1382 (1997).
19. Zheng, J., Ma, L., Xin, B., Olah, T., Humphreys, W. G. and Zhu, M.: Screening and identification of GSH-trapped reactive metabolites using hybrid triple quadruple linear ion trap mass spectrometry. Chem. Res. Toxicol., 20: 757-766 (2007).
20. Tang, W., Stearns, R. A., Wang, R. W., Chiu, S. L. and Baillie, T. A.: Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes: Identification of glutathione conjugated metabolites. Drug Metab. Dispos., 27: 365-372 (1999).
21. Maggs, J. L., Williams, D., Pirmohamed, M. and Park, B. K.: The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man. J. Pharmacol. Exp. Ther., 275: 1463-1475 (1995).
22. 14C]pulegone to microsomal proteins in vitro. Chem. Biol. Intract., 72: 325-333 (1989).
23. Thomassen, D., Slattery, J. T. and Nelson, S. D.: Menthofuran-dependent and independent aspects of pulegone hepatotoxicity: Role of glutathione. J. Pharmacol. Exp. Ther., 253: 567-572 (1990).
24. Meneses-Lorente, G., Sakatis, M. Z., Schulz-Utermoehl, T., De Nardi, C. and Watt, A. P.: A quantitative high-throughput trapping assay as a measurement of potential for bioactivation. Anal. Biochem., 351: 266-272 (2006).
25. Argoti, D., Liang, L., Conteh, A., Chen, L., Bershas, D., Yu, C., Vouros, P. and Yang, E.: Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chem. Res. Toxicol., 18: 1537-1544 (2005).
26. 1′(5′) iminium ion. J. Biol. Chem., 248: 2796-2800 (1973).
27. Gorrod, J. W. and Aislaitner, G.: The mechanism of alicyclic amines to reactive iminium ion intermediates. Eur. J. Drug Metab. Pharmacokinet., 19: 209-217 (1994).
28. Gorrod, J. W., Whittlesea, C. M. C. and Lam, S. P.: Trapping of reactive intermediates by incorporation of 14C-sodium cyanide during microsomal oxidation. Adv. Exp. Med. Biol., 283: 657-664 (1991).
29. Zhang, Z., Chen, Q., Li, Y., Doss, G. A., Dean, B. J., Ngui, J. S., Elipe, M. S., Kim, S., Wu, J. Y., DiNinno, F., Hammond, M. L., Stearns, R. A., Evans, D. C., Baillie, T. A. and Tang, W.: In vitro bioactivation of dihydrobenzoxathiin selective estrogen receptor modulators by cytochrome P450 3A4 in human liver microsomes: formation of reactive iminium and quinone type metabolites. Chem. Res. Toxicol., 18: 675-685 (2005).
30. Kassahun, K., Pearson, P. G., Tang, W., McIntosh, I., Leung, K., Elmore, C., Dean, D., Wang, R., Doss, G. and Baillie, T. A.: Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chem. Res. Toxicol., 14: 62-70 (2001).
31. Kalgutkar, A. S., Dalvie, D. K., Aubrecht, J., Smith, E. B., Coffing, S. L., Cheung, J. R., Vage, C., Lame, M. E., Chiang, P., McClure, K. F., Maurer, T. S., Coelho, R. V. Jr., oliman, V. F. and Childknegt, K.: Genotoxicity of 2-(3-chlorobenzyloxy)-6-(piperazinyl)pyrazine, a novel 5-hydroxytryptamine2c receptor agonist for the treatment of obesity: role of metabolic activation. Drug Metab. Dispos., 35: 848-858 (2007).
32. Silverman, R. B.: Mechanism-based Enzyme Inactivation: Chemistry and Enzymology. Boca Raton, CRC press, 1988, pp. 3-16.
33. Armstrong, R. N.: Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem. Res. Toxicol., 10: 2-18 (1997).
34. Anni, H., Pristatsky, P. and Israel, Y.: Binding of acetaldehyde to a glutathione metabolite: Mass spectrometric characterization of an acetaldehyde-cysteinylglycine conjugate. Alcohol Clin. Exp. Res., 27: 1613-1621 (2003).
35. Ratner, S. and Clarke, H. T.: The action of formaldehyde upon cysteine. J. Am. Chem. Soc., 59, 200-206 (1937).