Applications of Quadrupole Time-of-Flight Mass Spectrometry in Reactive Metabolite Screening

Mass Spectrometry in Drug Metabolism and Pharmacokinetics

Volumn , Issue , 2008, Pages 159-190

  Castro Perez, Jose M ^a  

^a WATERS CORPORATION   (United States)

Author keywords

Exact mass measurements and high resolution mass spectrometry; Quadrupole time of flight mass spectrometry application; Reactive drug metabolism and Q tof technology

Indexed keywords

EID: 84858381778     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470409817.ch4     Document Type: Chapter

References (71)

1. Agrawal, S., Winnik, B., Buckley, B., Mi, L., Chung, F.-L., and Cook, T. J. (2006). Simultaneous determination of sulforaphane and its major metabolites from biological matrices with liquid chromatography-tandem mass spectroscopy. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 840:99-107.
2. Antler, M. (2008). Fragment prediction and assignment for experimental mass spectra. In Proceedings of the 56th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, CO.
3. Baillie, T. A., and Davis, M. R. (1993). Mass spectrometry in the analysis of glutathione conjugates. Biol. Mass. Spectrom. 22:319-325.
4. Baillie, T. A., and Kassahun, K. (2001). Biological reactive intermediates in drug discovery and development: A perspective from the pharmaceutical industry. Adv. Exp. Med. Biol. 500:45-51.
5. Balogh, M. P. (2006). Spectral Interpretation, Part II: Tools of the trade. LCGC 24:762-769.
6. Bateman, K. P., Castro-Perez, J., Wrona, M., Shockcor, J. P., Yu, K., Oballa, R., and Nicoll-Griffith, D. A. (2007). MSE with mass defect filtering for in vitro and in vivo metabolite identification. Rapid Commun. Mass Spectrom. 21:1485-1496.
7. Bean, M. F., Pallante-Morell, S. L., Dulik, D. M., and Fenselau, C. (1990). Protocol for liquid chromatography/mass spectrometry of glutathione conjugates using postcolumn solvent modification. Anal. Chem. 62:121-124.
8. Chen, W. G., Zhang, C., Avery, M. J., and Fouda, H. G. (2001). Reactive metabolite screen for reducing candidate attrition in drug discovery. Adv. Exp. Med. Biol. 500:521-524.
9. Churchwell, M. I., Twaddle, N. C., Meeker, L. R., and Doerge, D. R. (2005). Improving LC-MS sensitivity through increases in chromatographic performance: Comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 825:134-143.
10. Clemmer, D. E., Valentine, S. J., Liu, X., Plasencia, M. D., Hilderbrand, A. E., Kurulugama, R. T., Koeniger, S. L. (2005). Developing liquid chromatography ion mobility mass spectrometry techniques. Expert Rev. Proteomics. 2(4):553-565.
11. Deterding, L. J., Srinivas, P., Mahmood, N. A., Burka, L. T., and Tomer, K. B. (1989). Fast atom bombardment and tandem mass spectrometry for structure determination of cysteine, N-acetylcysteine, and glutathione adducts of xenobiotics. Anal. Biochem. 183:94-107.
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(1):3-16.
13. Feng, W. Y. (2004). Mass spectrometry in drug discovery: A current review. Curr. Drug. Discov. Technol. 1:295-312.
14. Goodwin, L., White, S. A., and Spooner, N. (2007). Evaluation of ultra-performance liquid chromatography in the bioanalysis of small molecule drug candidates in plasma. J. Chromatogr. Sci. 45:298-304.
15. Guzey, C., and Spigset, O. (2004). Genotyping as a tool to predict adverse drug reactions. Curr. Top. Med. Chem. 4:1411-1421.
16. Hakala, K. S., Kostiainen, R., and Ketola, R. A. (2006). Feasibility of different mass spectrometric techniques and programs for automated metabolite profiling of tramadol in human urine. Rapid Commun. Mass Spectrom. 20:2081-2090.
17. Haroldsen, P. E., Reilly, M. H., Hughes, H., Gaskell, S. J., and Porter, C. J. (1988). Characterization of glutathione conjugates by fast atom bombardment/tandem mass spectrometry. Biomed. Environ. Mass. Spectrom. 15:615-621.
18. Herniman, J. M., Bristow, T. W. T., O'Connor, G., Jarvis, J., and Langley, G. J. (2004). Improved precision and accuracy for high-performance liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometric exact mass measurement of small molecules from the simultaneous and controlled introduction of internal calibrants via a second electrospray nebuliser. Rapid Commun. Mass Spectrom. 18:3035-3040.
19. Hop, C. E. C. A. (2004). Applications of quadrupole-time-of-flight mass spectrometry to facilitate metabolite identification. Am. Pharm. Rev. 7:76-79.
20. Jerkovitch, A. D., Mellors, J. S., and Jorgenson, J. W. (2003). Ultra performance liquid chromatography (UPLC): An introduction. LCGC 21:8-14.
21. Jindal, S. P., and Lutz, T. (1986). Ion cluster techniques in drug metabolism: Use of a mixture of labeled and unlabeled cocaine to facilitate metabolite identification. J. Anal. Toxicol. 10:150-155.
22. Johnson, K. A., and Plumb, R. (2005). Investigating the human metabolism of acetaminophen using UPLC and exact mass oa-TOF MS. J. Pharm. Biomed. Anal. 39:805-810.
23. 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.
24. Kalgutkar, A. S., et al. (2005). Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4. Drug Metab. Dispos. 33:243-253.
25. Kalgutkar, A. S., Obach, R. S., and Maurer, T. S. (2007). Mechanism-based inactivation of cytochrome p450 enzymes: Chemical mechanisms, structure-activity relationships and relationship to clinical drug-drug interactions and idiosyncratic adverse drug reactions. Curr. Drug. Metab. 8:407-447.
26. Kamel, A., and Prakash, C. (2006). High performance liquid chromatography/atmospheric pressure ionization/tandem mass spectrometry (HPLC/API/MS/MS) in drug metabolism and toxicology. Curr. Drug. Metab. 7:837-852.
27. Kind, T., and Fiehn, O. (2006). Metabolomic database annotations via query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm. BMC Bioinformat. 7:234.
28. Korfmacher, W. A. (2005). Foundation review: Principles and applications of LC-MS in new drug discovery. Drug Discov. Today 10:1357-1367.
29. Lasser, K. E., Allen, P. D., Woolhandler, S. J., Himmelstein, D. U., Wolfe, S. M., and Bor, D. H. (2002). Timing of new black box warnings and withdrawals for prescription medications. JAMA 287:2215-2220.
30. Lazarou, J., Pomeranz, B. H., and Corey, P. N. (1998). Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA 279:1200-1205.
31. Leclercq, L., Delatour, C., Hoes, I., Brunelle, F., Labrique, X., and Castro-Perez, J. (2005). Use of a five-channel multiplexed electrospray quadrupole time-of-flight hybrid mass spectrometer for metabolite identification. Rapid Commun. Mass Spectrom. 19:1611-1618.
32. Ma, S., and Subramanian, R. (2006). Detecting and characterizing reactive metabolites by liquid chromatography/tandem mass spectrometry. J. Mass Spectrom. 41:1121-1139.
33. Madsen, K. G., Olsen, J., Skonberg, C., Hansen, S. H., and Jurva, U. (2007). Development and evaluation of an electrochemical method for studying reactive phase-I metabolites:Correlation to in vitro drug metabolism. Chem. Res. Toxicol. 20:821-831.
34. McGibbon, G. A. (2008). Information extraction from full-scan LC/MS data using isotope patterns. In Proceedings of the 56th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, CO.
35. McGibbon, G. A., Bayliss, M. A., Antler, M., Lashin, V. (2008). Automated software analysis of isotope cluster mass differences for components in LC-MS datasets. In Proceedings of the 56th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, CO.
36. Mensch, J., Noppe, M., Adriaensen, J., Melis, A., Mackie, C., Augustijns, P., and Brewster, M. E. (2007). Novel generic UPLC/MS/MS method for high throughput analysis applied to permeability assessment in early drug discovery. J. Chromatogr. B. 847:182-187.
37. Miura, M., Tada, H., Satoh, S., Habuchi, T., and Suzuki, T. (2006). Determination of rabeprazole enantiomers and their metabolites by high-performance liquid chromatography with solid-phase extraction. J. Pharm. Biomed. Anal. 41:565-570.
38. Mortishire-Smith, R. J., O'Connor, D., Castro-Perez, J. M., and Kirby, J. (2005). Accelerated throughput metabolic route screening in early drug discovery using high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis. Rapid Commun. Mass Spectrom. 19:2659-2670.
39. Mortishire-Smith, R. J., Hill, A., and Castro-Perez, J. M. (2007). Generic dealkylation: A tool for increasing the hit-rate of metabolite identification, and customizing mass defect filters. In Proceedings of the 55th ASMS Conference on Mass Spectrometry and Allied Topics, Indianapolis, IN.
40. Mutlib, A., Lam, W., Atherton, J., Chen, H., Galatsis, P., and Stolle, W. (2005). Application of stable isotope labeled glutathione and rapid scanning mass spectrometers in detecting and characterizing reactive metabolites. Rapid Commun. Mass Spectrom. 19:3482-3492.
41. Naisbitt, D. J., Williams, D. P., Pirmohamed, M., Kitteringham, N. R., and Park, B. K. (2001). Reactive metabolites and their role in drug reactions. Curr. Opin. Allergy Clin. Immunol. 1:317-325.
42. Nassar, A. E., and Adams, P. E. (2003). Metabolite characterization in drug discovery utilizing robotic liquid-handling, quadruple time-of-flight mass spectrometry and in-silico prediction. Curr. Drug. Metab. 4:259-271.
43. Nassar, A. E., and Lopez-Anaya, A. (2004). Strategies for dealing with reactive intermediates in drug discovery and development. Curr. Opin. Drug. Discov. Devel. 7:126-136.
44. Nelson, S. D., Vaishnav, Y., Kambara, H., and Baillie, T. A. (1981). Comparative electron impact, chemical ionization and field desorption mass spectra of some thioether metabolites of acetaminophen. Biomed. Mass Spectrom. 8:244-251.
45. Park, B. K., Kitteringham, N. R., Powell, H., and Pirmohamed, M. (2000). Advances in molecular toxicology-Towards understanding idiosyncratic drug toxicity. Toxicology 153:39-60.
46. Park, B. K., Naisbitt, D. J., Gordon, S. F., Kitteringham, N. R., and Pirmohamed, M. (2001). Metabolic activation in drug allergies. Toxicology 158:11-23.
47. Park, K., Williams, D. P., Naisbitt, D. J., Kitteringham, N. R., and Pirmohamed, M. (2005). Investigation of toxic metabolites during drug development. Toxicol. Appl. Pharmacol. 207:425-434.
48. Pedraglio, S., Rozio, M. G., Misiano, P., Reali, V., Dondio, G., and Bigogno, C. (2007). New perspectives in bioanalytical techniques for preclinical characterization of a drug candidate:UPLC-MS/MS in in vitro metabolism and pharmacokinetic studies. J. Pharm. Biomed. Anal. 44:665-673.
49. Plumb, R., Mazzeo, J. R., Grumbach, E. S., Rainville, P., Jones, M., Wheat, T., Neue, U. D., Smith, B., and Johnson, K. A. (2007). The application of small porous particles, high temperatures, and high pressures to generate very high resolution LC and LC/MS separations. J. Sep. Sci. 30:1158-1166.
50. Ramanathan, R., Cao, K., Cavalieri, E., and Gross, M. L. (1998). Mass spectrometric methods for distinguishing structural isomers of glutathione conjugates of estrone and estradiol. J. Am. Soc. Mass Spectrom. 9:612-619.
51. Samuel, K., Yin,W., Stearns, R. A., Tang, Y. S., Chaudhary, A. G., Jewell, J. P., Lanza, T., Jr., Lin, L. S., Hagmann, W. K., Evans, D. C., and Kumar, S. (2003a). Addressing the metabolic activation potential of new leads in drug discovery: A case study using ion trap mass spectrometry and tritium labeling techniques. J. Mass Spectrom. 38:211-221.
52. Samuel, K., Yin,W., Stearns, R. A., Tang, Y. S., Chaudhary, A. G., Jewell, J. P., Lanza, T., Jr., Lin, L. S., Hagmann, W. K., Evans, D. C., and Kumar, S. (2003b). Addressing the metabolic activation potential of new leads in drug discovery: A case study using ion trap mass spectrometry and tritium labeling techniques. J. Mass Spectrom. 38:211-221.
53. Setoyama, T., Drijfhout, W. J., van de Merbel, N. C., Humphries, T. J., and Hasegawa, J. (2006). Mass balance study of [14C] rabeprazole following oral administration in healthy subjects. Int. J. Clin. Pharmacol. Ther. 44:557-565.
54. Shirley, M. A., Wheelan, P., Howell, S. R., and Murphy, R. C. (1997). Oxidative metabolism of a rexinoid and rapid phase II metabolite identification by mass spectrometry. Drug Metab. Dispos. 25:1144-1149.
55. Soglia, J. R., Contillo, L. G., Kalgutkar, A. S., Zhao, S., Hop, C. E. C. A., Boyd, J. G., and Cole, M. J. (2006). A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogs. Chem. Res. Toxicol. 19:480-490.
56. Thalassinos, K., et al. (2004). Ion mobility mass spectrometry of proteins in a modified commercial mass spectrometer. Int. J. Mass Spectrom. 236(1-3):55-63.
57. Tiller, P. R., Yu, S., Castro-Perez, J., Fillgrove, K. L., and Baillie, T. A. (2008). Highthroughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time-of-flight system as a 'first-line' approach for metabolite identification studies. Rapid Commun. Mass Spectrom. 22:1053-1061.
58. Uetrecht, J. (2003). Screening for the potential of a drug candidate to cause idiosyncratic drug reactions. Drug Discov. Today 8:832-837.
59. van Deemter, J. J., Zuiderweg, F. J. and Klinkenbergm, A. (1956). A. Longitudinal diffusion and resistance to mass transfer as causes of nonideality in chromatography. Chem. Eng. Sci. 5:271-289.
60. Williams, D. P., Kitteringham, N. R., Naisbitt, D. J., Pirmohamed, M., Smith, D. A., and Park, B. K. (2002). Are chemically reactive metabolites responsible for adverse reactions to drugs? Curr. Drug. Metab. 3:351-366.
61. Williams, J. P., Lock, R., Patel, V. J., and Scrivens, J. H. (2006). Polarity switching accurate mass measurement of pharmaceutical samples using desorption electrospray ionization and a dual ion source interfaced to an orthogonal acceleration time-of-flight mass spectrometer. Anal. Chem. 78:7440-7445.
62. Wolf, D. E., VandenHeuvel, J. A., Tyler, T. R., Walker, R. W., Koniuszy, F. R., Gruber, V., Arison, B. H., Rosegay, A., Jacob, T. A., and Wolf, F. J. (1980). Identification of a glutathione conjugate of cambendazole formed in the presence of liver microsomes. Drug Metab. Dispos. 8:131-136.
63. Wrona, M., Timo, M., Bateman, K. P., Mortishire-Smith, R. J., and O'Connor, D. (2005). All-in-one analysis for metabolite identification using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry with collision energy switching. Rapid Commun. Mass Spectrom. 19:2597-2602.
64. Wu, N., Lippert, J. A., and Lee, M. L. (2001). Practical aspects of ultrahigh pressure capillary liquid chromatography. J. Chromatogr. A 911:1-12.
65. Wyndham, K. D., O'Gara, J. E., Walter, T. H., Glose, K. H., Lawrence, N. L., Alden, B. A., Izzo, G. S., Hudalla, C. J., and Iraneta, P. C. (2003). Characterization and evaluation of C18 HPLC stationary phases based on ethyl-bridged hybrid organic/inorganic particles. Anal. Chem. 75:6781-6788.
66. Yan, Z., and Caldwell, G. W. (2004). Stable-isotope trapping and high-throughput screenings of reactive metabolites using the isotope MS signature. Anal. Chem. 76:6835-6847.
67. Yan, Z., Maher, N., Torres, R., and Huebert, N. (2007). Use of a trapping agent for simultaneous capturing and high-throughput screening of both "soft" and "hard" reactive metabolites. Anal. Chem. 79:4206-4214.
68. Zhang, H., Zhang D., and Ray K. (2003). A software filter to remove interference ions from drug metabolites in accurate mass liquid chromatography/mass spectrometric analyses. J. Mass Spectrom. 38:1110-1112.
69. Zheng, J., Ma, L., Xin, B., Olah, T., Humphreys, W., and Zhu, M. (2007). Screening and Identification of GSH-trapped reactive metabolites using hybrid triple quadruple linear ion trap mass spectrometry. Chem. Res. Toxicol. 20:757-766.
70. Zhou, S., Song, Q., Tang, Y., and Naidong, W. (2005). Critical review of development, validation, and transfer for high throughput bioanalytical LC-MS/MS methods. Curr. Pharm. Anal. 1:3-14.
71. Zhu, M., Ma, L., Zhang, H., and Humphreys, W. G. (2007). Detection and structural characterization of glutathione-trapped reactive metabolites using liquid chromatographyhigh-resolution mass spectrometry and mass defect filtering. Anal. Chem. 79:8333-8341.