Strategy for Structure Elucidation of Drug Metabolites Derived from Protonated Molecules and (MS)n Fragmentation of Zotepine, Tiaramide and their Metabolites

Drug Metabolism and Pharmacokinetics

Volumn 17, Issue 4, 2002, Pages 316-339

  Tozuka, Zenzaburo ^a   Kaneko, Hayato ^a   Shiraga, Toshifumi ^a   Mitani, Yasuyuki ^a   Kawamura, Akio ^a   Kagayama, Akira ^a   Aoba, Anri ^b  

^a ASTELLAS PHARMA INC   (Japan)

^b ST MARIANNA UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

(MS) fragmentation; drug metabolism; ESI MS; protonated molecules; structure elucidation

Indexed keywords

EID: 84987948914     PISSN: 13474367     EISSN: 18800920     Source Type: Journal    
DOI: 10.2133/dmpk.17.316     Document Type: Article

References (25)

1. Tozuka, Z.: Electrospray ionization mass spectrometry of noncovalent or covalent binding complexes of drugs with proteins. J. Mass Spectrom. Soc. Jpn., 48: 211-220 (2000).
2. Tozuka, Z., Iwasaki, K., Kobayashi, M., Matsuda, H., Suzuki, A., Noda, K., McManus, K. T., and Garteiz, D. A.: Determination of FK506 in blood by electrospray LC/MS. In Matsuo T. (ed): Proceedings of the Kyotó92Iinternational Conference on Biological Mass Spectrometry, Kyoto, San-ei Publishing Co. 1992, pp.430-431.
3. Tozuka, Z.: Know-how of the high sensitivity quantitative analysis of drug by LC/API/MS. J. Mass Spectrom. Soc. Jpn., 45: 377-399(1997).
4. Tozuka, Z.: Quantitative analysis by ESI LC /MS. In Ueno, T., Hirayama, K., and Harada, K., (eds): Biological Mass Spectrometry, Tokyo, Tokyo Kagakudoujin, 1997, pp.289-299.
5. Tozuka, Z.: Pretreatment for quantitative analysis. J. Mass Spectrom. Soc. Jpn., 47: 229-245 (1999).
6. Tozuka, Z.: Quality control of analytical method by mass spectrometry. J. Mass Spectrom. Soc. Jpn., 48: 134-140 (1999).
7. Uchida, S., Honda, F., Otsuka, M., Satoh, Y., Mori, J., Ono, T. and Hitomi, M.: Pharmacological study of [2-chloro-11-(2-dimethylaminoethoxy)dibenzo [b, f]thiepine] (zotepine), a new neuroleptic drug. Arzneimittel-Por-chung/Drug Research, 29: 1588-1594 (1979).
8. Noda, K., Suzuki, A., Okui, M., Noguchi, H., Nishiura, M. and Nishiura, N.: Pharmacokinetics and drug metabolism of [2-chloro-11-(2-dimethylamino ethox-y)dibenzo[b, f]thiepine](zotepine) in rat, mouse, dog and man. Arzneimittel-Porchung/drug Research, 29: 1595-1600 (1979).
9. Okada, R., Morokawa, Y., Yanagida, H., Ohoki, M., Udagawa, I., Tanabe, Y., Gen, K., Sanaka, T., Watanabe, H., Ohota, T., Uemura, M., Kosaka, K., Yamaguchi, N., Tanaka, C., Usui, Y., Tozuka, Z. and Aoba, A.: Relationship between the anti-dopamine activity and the plasma concentration of zotepine and its metabolites in schizophrenia patients. Abstract of the 8th Annual Meeting of JSCN, 1998, pp.50.
10. Tozuka, Z., Shiraga, T., Hata, T., Shirai, Y., Morokawa, Y., Yamaguchi, N. and Aoba, A.: LC/ESI/ MS analysis of zotepine and its metabolites in plasma of patients administered zotepine and in vitro metabolites of zotepine with human liver microsome. Abstract of the 8th Annual Meeting of JSCN, 1998, pp.56.
11. Shiraga, T., Kaneko, H., Iwasaki, K., Tozuka, Z., Suzuki, A. and Hata, T.: Identification of cytochrome P450 enzymes involved inthe metabolism of zotepine, an antipsychotic drug in human liver microsomes. Xenobiotica, 29: 217-229 (1999).
12. Ohoki, M., Morokawa, Y., Okada, R., Yanagida, H., Udagawa, I., Tanabe, Y., Gen, K., Sanaka, T., Watanabe, H., Ohota, T., Uemura, M., Kosaka, K., Yamaguchi, N., Tanaka, C., Usui, Y., Tozuka, Z. and Aoba, A.: Study on the anti 5-HT2 activity and anti D2 activity of zotepine and its metabolites. Abstract of the 8th Annual Meeting of JSCN, 1998, pp.49.
13. Tsurumi, K., Hiramatsu, Y., Nozaki, M., Hayashi, M. and Fujimura, H.: Pharmacological study of 4-[(5-chloro-2-oxo-3(2H)-benzothiazoyl)acetyl]-1- piperazine ethanol, is an anti-inflammatory drug. Arzneimittel-Por-chung/Drug Research, 22: 716-721(1972).
14. Noguchi, H., Okui, M., Noda, K. and Kato, R.: Disposition and metabolic fate of tiaramide hydrochloride, a new anti-inflammatoryagent, in the rat. Xenobiotica, 7: 491-503 (1977).
15. Audier, H. E., Milliet, A., Perret, C., Tabet, J. C. and Varenne, P.: Mecanismes de fragmentation en spectromemetrie de mass par ionization chemique III Ions formes par cyclisation. Org. Mass Spectrom., 13: 315-318 (1978).
16. Sigsby, M. L., Day, R. J. and Cooks, R. G., Fragmentation of even electron ions. Protonated ketones and ethers. Org. Mass Spectrom. 14: 273-280 (1979).
17. Jardine, I. and Fenselau, C.: Proton localization in chemical ionization fragmentation. J. Am. Chem. Soc., 98: 5086-5089 (1976).
18. Michinowicz, J. and Munson, B.: Studies in chemical ionization mass spectrometry: 17-hydroxy steroid. Org. Mass Spectrom., 6: 765-783 (1972).
19. Michinowicz, J. and Munson, B.: Studies in chemical ionization mass spectrometry: Steroidal ketones. Org. Mass Spectrom., 8: 49-60 (1974).
20. Longevialle, P., Milne, G. W. A. and Fales, H. M.: Chemical ionization mass spectrometry of complex molecules. XI. Stereochemicaland conformational effects in the isobutane chemical ionization mass spectra of some steroidal amino alcohols. J. Am. Chem. Soc., 95: 6666-6669 (1973).
21. Longevialle, P., Girard, J., Rossi, J. and Tichy, M.: Influence of the inter-functional distance on the dehydration of amino alcohols in iso-butane chemical ionization mass spectrometry. Org. Mass Spectrom., 14: 414-416 (1979).
22. Nakata, H.: A fundamental aspect of the structure and fragmentations of protonation of organic compounds and the behavior of resulting protonated molecules. J. Mass Spectrom. Soc. Jpn., 48: 79-93 (1999).
23. Dalvie, D. K. and óDonnell, J. P.: Metabolism of CP-195, 543, a leukotriene B4 receptor antagonist, in the Long-Evans rat and Cynomolgous monkey. Xenobiotica, 29: 1123-1140 (1999).
24. Wu, W. N., Mckown, L. A., Moyer, M. D., Johannsen, T. B. and Takacs, A. R. In vitro metabolism of mifepristone (RU-486) in rat, monkey and human hepatic S9 fractions: identification of three new mifepristone metabolites. Xenobiotica, 29: 1089-1100 (1999).
25. Tozuka, Z.: Application of mass spectrometry and quality control, Dokusei Shitsumon Bako No.4., Tokyo. Scientist Co., Ltd. 40-59(2001).