Applications of Mass Spectrometry for the Characterization of Reactive Metabolites of Drugs in Discovery

Integrated Strategies for Drug Discovery Using Mass Spectrometry

Volumn , Issue , 2005, Pages 289-313

  Wang, Jim ^a   Wang, Jack ^a   Davis, Margaret ^a   Demaio, William ^a   Scatina, Joann ^a   Talaat, Rasmy ^a  

^a PFIZER INC   (United States)

Author keywords

Acyl glucouronide; Bioactivation; Derivatization; Deuterium exchange; LC MS; Metabolism; Quinone; Reactive metabolites; Thiophene; Toxicity; Trapping agents

Indexed keywords

EID: 84889448802     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/0471721034.ch10     Document Type: Chapter

References (42)

1. Guengerich, F.P. "Common and Uncommon Cytochrome P450 Reactions Related to Metabolism and Chemical Toxicity," Chem. Res. Toxicol. 14(6), 611-615 (2001).
2. Cohen, S.D.; Pumford, N.R.; Khairallah, E.A.; Boekelheide, K.; Pohl, L.R.; Amouzadeh, H.R.; Hinson, J.A. "Selective Protein Covalent Binding and Target Organ Toxicity," Toxicol. Appl. Pharmacol. 143, 1-12 (1997).
3. Pumford, N.R.; Halmes, N.C. "Protein Targets of Xenobiotic Reactive Intermediates," Ann. Rev. Pharmacol. Toxicol. 37, 91-117 (1997).
4. Koen, Y.M.; Hanzlik, R.P. "Identification of Seven Proteins in the Endoplasmic Reticulum as Targets for Reactive Metabolites of Bromobenzene," Chem. Res. Toxicol. 15, 699-706 (2001).
5. Uetrecht, J. "Prediction of a New Drug's Potential to Cause Idiosyncratic Reactions," Curr. Opin. Drug Disc. Devel. 4(1), 55-59 (2001).
6. Baughman, T.M.; Wells-Knecht, M.; Wells-Knecht, K.; Zhao, Z. "Method Validation for a Glutathione-trapping Reactive Metabolite Assay Using Drugs with Structural Moieties Known to Produce Reactive Species," Drug Metab. Rev. 35(S2), 112 (2003).
7. Cai, C.; Stankovic, C.; Gifford, E.; Surendran, N.; Cai, H. "Radiolabeled Glutathione Assay: Method Development and Its Applications," Drug Metab. Rev. 35(S2), 110 (2003).
8. Skonberg, C.; Sidenius, U.; Olsen, J.; Hansen, S.H. "In Vitro Reactivities of Carboxylic Acid-CoA Thioesters with Glutathione," Drug Metab. Rev. 35(S2), 105 (2003).
9. Homberg, J.C.; Andre, C.; Abuaf, N. "A New and Anti-liver Kidney Microsome Antibody in Tienilic Acid Induced Hepatitis," Clin. Exp. Immunol. 55, 561-570 (1984).
10. Valadon, P.; Dansette, P.M.; Girault, J.P.; Amar, C.; Mansuy, D. "Thophene Sulfoxides as Reactive Metabolites: Formation upon Microsomal Oxidation of a 3-Aroylthiophene and Fate in the Presence of Nucleophiles In Vitro and In Vivo," Chem. Res. Toxicol. 9, 1403-1413 (1996).
11. Bakke, O.M.;Wardell,W.M.; de Abayo, F.; Kaitin, K.I.; Lasagna, L. "Drug Safety Discontinuations in the United Kingdom, the United States, and Spain from 1974 through 1993: A Regulatory Perspective," Clin. Pharmacol. Ther. 58, 108-117 (1994).
12. O'Donnell, J.P.; Dalvie, D.K.; Kalgutkar, A.S.; Obach, R.S. "Mechanismbased Inactivation of Human Recombinant P450 2C9 by the Nonsteroidal Anti-inflammatory Drug Suprofen," Drug Metab. Dispos. 31, 1369-1377 (2003).
13. Hass, W.K.; Easton, J.D.; Adams, H.P.; Pryse-Phillips, W.; Molony, B.A.; Anderson, S.; Kamm, B. "A Randomized Trial Comparing Ticlopidine Hydrochloride with Aspirin for the Prevention of Stroke in High Risk Patients," N. Engl. J. Med. 321, 501-507 (1989).
14. Ono, K.;Kurohara, K.;Yoshihara, M.; Shimamoto,Y.;Yamaguchi, M. "Agranulocytosis Caused by Ticlopidine and Its Mechanism," Am. J. Hematol. 37, 239-242 (1991).
15. Tsatala, C.; Chalkia, P.; Garyfallos, A.; Kakoulidis, I.; Xanthakis, I. "Ticlopidine Induced Aplastic Anemia: Case Report and Review of the Literature," Clin. Drug Invest. 9, 127-130 (1995).
16. Liu, X.C.; Uetrecht, J.P. "Metabolism of Ticlopidine by Activated Neutrophils: Implications for Ticlopidine-induced Agranulocytosis," Drug Metab. Dispos. 28, 726-730 (2000).
17. Scouten, W.H.; Lubcher, R.; Baughman, W. "N-Dansylaziridine: A New Fluorescent Modification for Cysteine Thiols" Biochem. Biophys. Acta. 336, 421-426 (1974).
18. Bailey, M.J.; Dickinson, R.G. Acyl Glucuronide Reactivity in Perspective: Biological Consequences. [Review] [138 refs]. Chemico-Biol. Interac. 145(2), 117-137 (2003).
19. Akira, K.; Uchijima, T.; Hashimoto, T. "Rapid Internal Acyl Migration and Protein Binding of Synthetic Probenecid Glucuronides," Chem. Res. Toxicol. 15(6), 765-772 (2002).
20. Dansette, P.M.; Bonierbale, E.; Minoletti, C.; Beaune, P.H.; Pessayre, D.; Mansuy, D. "Drug-induced Immunotoxicity," Eur. J. Drug Metab. Pharmacokinet. 23, 443-451 (1998).
21. Faed, E.M. "Properties of Acyl Glucuronides: Implications for Studies of the Pharmacokinetics and Metabolism of Acidic Drugs," Drug Metab. Dispos. 15, 1213-1249 (1984).
22. Park, B.K.; Coleman, J.W.; Kitteringham, N.R. "Drug Disposition and Drug Hypersensitivity," Biochem. Pharmacol. 36, 581-590 (1987).
23. Riley, R.J.; Leeder, J.S. "In Vitro Analysis of Metabolic Predisposition to Drug Hypersensitivity Reactions," Clin. Exp. Immunol. 99, 1-6 (1995).
24. Spahn-Langguth, H.; Dahms, M.; Hermening, A. "Acyl Glucuronides, Covalent Binding and Its Potential Relevance," Adv. Exp. Med. Biol. 387, 313-328 (1996).
25. Spahn-Langguth, H.; Benet, L.Z. "Acyl Glucuronides Revisited: Is the Glucuronidation Process a Toxification as Well as a Detoxification Mechanism?" Drug Metab. Rev. 24, 5-48 (1992).
26. Benet, L.Z.; Spahn-Langguth, H.; Iwakawa, S.; Volland, C.; Mizuma, T.; Mayer, S.; Mutschler, E.; Lin, E.T. "Predictability of the Covalent Binding of Acidic Drugs in Man," Life Sci. 53, 141-146 (1993).
27. Bolze, S.; Bromet, N.; Gay-Feutry, C.; Massiere, F.; Boulieu, R.; Hulot, T. "Development of an In Vitro Screening Model for the Biosynthesis of Acyl Glucuronide Metabolites and the Assessment of Their Reactivity Toward Human Serum Albumin," Drug Metab. Dispos. 30, 404-413 (2002).
28. Castillo, M.; Smith, P.C. "Covalent Binding of Ibuprofen Acyl Glucuronide to Human Serum Albumin In Vitro," Pharm Res. 10(S2), 42 (1991).
29. Dubois, N.; Lapicque, F.; Magdalou, J.; Abiteboul, M.; Netter, P. "Stereoselective Binding of the Glucuronide of Ketoprofen Enantiomers to Human Serum Albumin," Biochem. Pharmacol. 48, 1693-1699 (1994).
30. Rachmel, A.; Hazelton, G.A.; Yergey, A.L.; Liberato, D.J. "Furosemide 1-Oacyl Glucuronide. In Vitro Biosynthesis and pH-dependent Isomerization to β-Glucuronidase-resistant Forms," Drug Metab. and Dispos. 13(6), 705-710 (1985).
31. Ojingwa, J.C.; Spahn-Langguth, H.; Benet, L.Z. "Studies of Tolmetin Reversible and Irreversible Binding to Proteins via Its Glucuronide Conjugates," Pharm. Res. 5(S2), 14 (1988).
32. Ojingwa, J.C.; Spahn-Langguth, H.; Benet, L.Z. "Irreversible Binding of Tolmetin to Macromolecules via Its Glucuronide: Binding to Blood Constituents, Tissue Homogenates and Subcellular Fractions In Vitro," Xenobiotica 24, 495-506 (1994).
33. Tang,W. "The Metabolism of Diclofenac, Enzymology and Toxicology Perspectives," Curr. Drug Metab. 4(4), 319-329 (2003).
34. Volland, C.; Sun, H., Dammeyer, J.; Benet, L.Z. "Stereoselective Degradation of the Fenoprofen Acyl Glucuronide Enantiomers and Irreversible Binding to Plasma Protein," Drug Metab. Dispos. 19(6), 1080-1086 (1991).
35. Bailey, M.J.; Worrall, S.; de Jersey, J.; Dickinson, R.G. "Zomepirac Acyl Glucuronide Covalently Modifies Tubulin In Vitro and In Vivo and Inhibits Its Assembly in an In Vitro System," Chemico-Biol. Interac. 115(2), 153-166 (1998).
36. Kretz-Rommel, A.; Boelsterli, U.A. "Diclofenac Covalent Protein Binding is Dependent on Acyl Glucuronide Formation and is Inversely Related to P450-mediated Acute Cell Injury in Cultured Rat Hepatocytes," Toxicol. Appl. Pharmacol. 120(1), 155-161 (1993).
37. Dickinson, R.G.; King, A.R. "Studies on the Reactivity of Acyl Glucuronides. V. Glucuronide-derived Covalent Binding of Diflunisal to Bladder Tissue of Rats and Its Modulation by Urinary pH and Beta-glucuronidase," Biochem. Pharmacol. 46(7), 1175-1182 (1993).
38. Seitz, S.; Boelsterli, U.A. "DiclofenacAcyl Glucuronide, a Major Biliary Metabolite, Is Directly Involved in Small Intestinal Injury in Rats," Gastroenterol. 115(6), 1476-1482 (1998).
39. Boelsterli, U.A.; Zimmerman, H.J.; Kretz-Rommel, A. "Idiosyncratic Liver Toxicity of Nonsteroidal Antiinflammatory Drugs: Molecular Mechanisms and Pathology," Crit. Rev. Toxicol. 25(3), 207-235 (1995).
40. Smith, P.C.; McDonagh, A.F.; Benet, L.Z. "Irreversible Binding of Zomepirac to Plasma Protein In Vitro and In Vivo," J. Clin. Invest. 77, 934-939 (1986).
41. Kretz-Rommel, A.; Boelsterli, U.A. "Mechanism of Covalent Adduct Formation of Diclofenac to Rat Hepatic Microsomal Proteins. Retention of the Glucuronic Acid Moiety in the Adduct," Drug Metab Dispos. 22, 956-961 (1994).
42. Van Breeman, R.B.L.; Fenselau, C. "Acylation of Albumin by 1-O-acyl Glucuronides," Drug Metab. Dispos. 13, 318-320 (1985).