A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogues

Chemical Research in Toxicology

Volumn 19, Issue 3, 2006, Pages 480-490

  Soglia, John R ^a   Contillo, Leonard G ^a   Kalgutkar, Amit S ^a   Zhao, Sabrina ^a   Hop, Cornelis E C A ^a   Boyd, James G ^a   Cole, Mark J ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; FLUTAMIDE; GLUTATHIONE DERIVATIVE; PARACETAMOL; QUATERNARY AMMONIUM DERIVATIVE; QUATERNARY AMMONIUM GLUTATHIONE DERIVATIVE CONJUGATING AGENT; UNCLASSIFIED DRUG;

ARTICLE; CALCULATION; CHEMICAL STRUCTURE; DRUG ACTIVATION; DRUG CONJUGATION; FEASIBILITY STUDY; LINEAR REGRESSION ANALYSIS; LIQUID CHROMATOGRAPHY; METABOLITE; QUANTITATIVE ASSAY; REACTION ANALYSIS; STANDARD; STRUCTURE ANALYSIS; SYNTHESIS; TANDEM MASS SPECTROMETRY;

ACETAMINOPHEN; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CLOZAPINE; FEMALE; FLUTAMIDE; GLUTATHIONE; HUMANS; MALE; MASS SPECTROMETRY; MICROSOMES, LIVER; PEPTIDES; QUATERNARY AMMONIUM COMPOUNDS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 33645469797     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx050303c     Document Type: Article

References (43)

1. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., Dorato, M., Van Deun, K., Smith, P., Berger, B., and Heller, A. (2000) Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul. Toxicol. Pharmacol. 32, 56-67.
2. Ju, C., and Uetrecht, J. P. (2002) Mechanism of idiosyncratic drug reactions: Reactive metabolite formation, protein binding and the regulation of the immune system. Curr. Drug Metab. 3, 367-377.
3. Uetrecht, J. P. (2000) Is it possible to more accurately predict which drug candidates will cause idiosyncratic drug reactions? Curr. Drug Metab. 1, 133-141.
4. Welch, K. D., Wen, B., Goodlett, D. R., Yi, E. C., Lee, H., Reilly, T. P., Nelson, S. D., and Pohl, L. R. (2005) Proteomic identification of potential susceptibility factors in drug-induced liver disease. Chem. Res. Toxicol. 18, 924-933.
5. Liebler, D. C., and Guengerich, F. P. (2005) Elucidating mechanisms of drug-induced toxicity. Nat. Rev. Drug Discovery 4, 410-420.
6. Nelson, S. D. (2001) Structure toxicity relationships-How useful are they in predicting toxicities of new drugs? Adv. Exp. Med. Biol. 500, 33-43.
7. Guengerich, F. P. (2005) Principles of covalent binding of reactive metabolites and examples of activation of bis-electrophiles by conjugation. Arch. Biochem. Biophys. 433, 369-378.
8. Marnett, L. J. (2002) Oxy radicals, lipid peroxidation and DNA damage. Toxicology 181-182, 219-222.
9. Park, B. K., Kitteringham, N. R., Maggs, J. L., Pirmohamed, M., and Williams, D. P. (2005) The role of metabolic activation in drug-induced hepatotoxicity. Annu. Rev. Pharmacol. Toxicol. 45, 177-202.
10. Uetrecht, J. P. (1999) New concepts in immunology relevant to idiosyncratic drug reactions: The "danger hypothesis" and innate immune system. Chem. Res. Toxicol. 12, 387-395.
11. Cohen, S. D., Pumford, N. R., Khairallah, E. A., Boekelheide, K., Pohl, L. R., Amouzadeh, H. R., and Hinson, J. A. (1997) Selective protein covalent binding and target organ toxicity. Toxicol. Appl. Pharmacol. 143, 1-12.
12. Evans, D. C., Watt, A. P., Nicoll-Griffith, D. A., and Baillie, T. A. (2004) Drug-protein adducts: An industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem. Res. Toxicol. 17, 3-16.
13. Kalgutkar, A. S., Gardner, I., Obach, R. S., Shaffer, C. L., Callegari, E., Henne, K. R., Mutlib, A. E., Dalvie, D. K., Lee, J. S., Nakai, Y., O'Donnell, J. P., Boer, J., and Harriman, S. P. (2005) A comprehensive listing of bioactivation pathways of organic functional groups. Curr. Drug Metab. 6, 161-225.
14. Kalgutkar, A. S., Dalvie, D. K., O'Donnell, J. P., Taylor, T. J., and Sahakian, D. C. (2002) On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics. Curr. Drug Metab. 3, 379-424.
15. Kalgutkar, A. S., and Soglia, J. R. (2005) Minimizing the potential for metabolic activation in drug discovery. Exp. Opin. Drug Metab. Toxicol 1, 91-141.
16. Homberg, J. C., Andre, C., and Abuaf, N. (1984) A new anti-liver-kidney microsome antibody (anti-LKM2) in tienilic acid-induced hepatitis. Clin. Exp. Immunol. 55, 561-570.
17. Bourdi, M., Larrey, D., Nataf, J., Bernuau, J., Pessayre, D., Iwasaki, M., Guengerich, F. P., and Beaune, P. H. (1990) Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis. J. Clin. Invest. 85, 1967-1973.
18. Doniach, D. (1970) Cell-mediated immunity in halothane hypersensitivity. N. Engl. J. Med. 283, 315-316.
19. Nassif, A., Bensussan, A., Dorothee, G., Mami-Chouaib, F., Bachot, N., Bagot, M., Boumsell, L., and Roujeau, J. C. (2002) Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. J. Invest. Dermatol. 118, 728-733.
20. Beaune, P., Dansette, P. M., Mansuy, D., Kiffel, L., Finck, M., Amar, C., Leroux, J. P., and Homberg, J. C. (1987) Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc. Natl. Acad. Sci. U.S.A. 84, 551-555.
21. Bourdi, M., Tinel, M., Beaune, P. H., and Pessayre, D. (1994) Interactions of dihydralazine with cytochromes P4501A: A possible explanation for the appearance of anti-cytochrome P4501A2 autoantibodies. Mol. Pharmacol. 45, 1287-1295.
22. Bourdi, M., Chen, W., Peter, R. M., Martin, J. L., Buters, J. T., Nelson, S. D., and Pohl, L. R. (1996) Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem. Res. Toxicol. 9, 1159-1166.
23. Gorrod, J. W., Whittlesea, C. M., and Lam, S. P. (1991) Trapping of reactive intermediates by incorporation of 14C-sodium cyanide during microsomal oxidation. Adv. Exp. Med. Biol. 283, 657-664.
24. Sahali-Sahly, Y., Balani, S. K., Lin, J. H., and Baillie, T. A. (1996) In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4. Chem. Res. Toxicol. 9, 1007-1012.
25. Baillie, T. A., Pearson, P. G., Rashed, M. S., and Howald, W. N. (1989) The use of mass spectrometry in the study of chemically reactive drug metabolites. Application of MS/MS and LC/MS to the analysis of glutathione- and related S-linked conjugates of N-methylformamide. J. Pharm. Biomed. Anal. 7, 1351-1360.
26. Madden, S., Spaldin, V., Hayes, R. N., Woolf, T. F., Pool, W. F., and Park, B. K. (1995) Species variation in the bioactivation of tacrine by hepatic microsomes. Xenobiotica 25, 103-116.
27. Soglia, J. R., Harriman, S. P., Zhao, S., Barberia, J., Cole, M. J., Boyd, J. G., and Contillo, L. G. (2004) The development of a higher throughput reactive intermediate screening assay incorporating microbore liquid chromatography-micro-electrospray ionization-tandem mass spectrometry and glutathione ethyl ester as an in vitro conjugating agent. J. Pharm. Biomed. Anal. 36, 105-116.
28. Thompson, D. C., Perera, K., and London, R. (1995) Quinone methide formation from para isomers of methylphenol (cresol), ethylphenol, and isopropylphenol: relationship to toxicity. Chem. Res. Toxicol. 8, 55-60.
29. Gan, J., Harper, T. W., Hsueh, M. M., Qu, Q., and Humphreys, W. G. (2005) Dansyl glutathione as a trapping agent for the quantitative estimation and identification of reactive metabolites. Chem. Res. Toxicol. 18, 896-903.
30. Iavarone, A. T., and Williams, E. R. (2002) Mechanism of charging and supercharging molecules in electrospray ionization. J. Am. Chem. Soc. 125, 2319-2327.
31. Hinson, J. A., Reid, A. B., McCullough, S. S., and James, L. P. (2004) Acetaminophen-induced hepatotoxicity: Role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab. Rev. 36, 805-822.
32. Kaplowitz, N. (2005) Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discovery 4, 489-499.
33. Hummer, M., Kurz, M., Kurzthaler, I., Oberbauer, H., Miller, C., and Fleischhacker, W. W. (1997) Hepatotoxicity of clozapine. J. Clin. Psychopharmacol. 17, 314-317.
34. Wysowski, D. K., Freiman, J. P., Tourtelot, J. B., Horton, M. L., III (1993) Fatal and nonfatal hepatotoxicity associated with flutamide. Ann. Intern. Med. 118, 860-864.
35. Maggs, J. L., Williams, D., Pirmohamed, M., and Park, B. K. (1995) The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man. J. Pharmacol. Exp. Ther. 275, 1463-1475.
36. Berson, A., Wolf, C., Chachaty, C., Fisch, C., Fau, D., Eugene, D., Loeper, J., Gauthier, J. C., Beaune, P., and Pompon, D. (1993) Metabolic activation of the nitroaromatic antiandrogen flutamide by rat and human cytochromes P-450, including forms belonging to the 3A and 1A subfamilies. J. Pharmacol. Exp. Ther. 265, 366-372.
37. Baillie, T. A., and Davis, M. R. (1993) Mass spectrometry in the analysis of glutathione conjugates. Biol. Mass Spectrom. 22, 319-325.
38. Aizawa, Y., Ikemoto, I., Kishimoto, K., Wada, T., Yamazaki, H., Ohishi, Y., Kiyota, H., Furuta, N., Suzuki, H., and Ueda, M. (2003) Flutamide-induced hepatic dysfunction in relation to steady-state plasma concentrations of flutamide and its metabolites. Mol. Cell. Biochem. 252, 149-156.
39. Takashima, E., Iguchi, K., Usui, S., Yamamoto, H., and Hirano, K. (2003) Metabolite profiles of flutamide in serum from patients with flutamide-induced hepatic dysfunction. Biol. Pharm. Bull. 26, 1455-1460.
40. Shet, M. S., McPaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. (1997) Metabolism of the antiandrogenic drug (flutamide) by human CYP1A2. Drug Metab. Dispos. 25, 1298-1303.
41. Armstrong, R. N. (1997) Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem. Res. Toxicol. 10, 2-18.
42. Kassahun, K., Pearson, P. G., Tang, W., McIntosh, I., Leung, K., Elmore, C., Dean, D., Wang, R., Doss, G., and Baillie, T. A. (2001) 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.
43. Erve, J. C., Svensson, M. A., von Euler-Chelpin, H., and Klasson-Wehler, E. (2004) Characterization of glutathione conjugates of the remoxipride hydroquinone metabolite NCQ-344 formed in vitro and detection following oxidation by human neutrophils. Chem. Res. Toxicol. 17, 564-571.