Analytical Science and Technology (분석과학)

The Korean Society of Analytical Sciences (한국분석과학회)
권호 표지
DOI QR코드

DOI QR Code

Electrospray ionization tandem mass fragmentation pattern of camostat and its degradation product, 4-(4-guanidinobenzoyloxy)phenylacetic acid

Camostat 및 분해산물 4-(4-guanidinobenzoyloxy)phenylacetic acid의 전자분무 이온화 텐덤 질량 fragmentation 패턴

  • Kwon, Soon-Ho (Department of Bioanalysis, Seoul Medical Science Institute & Seoul Clinical Laboratories) ;
  • Shin, Hye-Jin (Department of Bioanalysis, Seoul Medical Science Institute & Seoul Clinical Laboratories) ;
  • Park, Ji-Myeong (Department of Bioanalysis, Seoul Medical Science Institute & Seoul Clinical Laboratories) ;
  • Lee, Kyoung-Ryul (Department of Bioanalysis, Seoul Medical Science Institute & Seoul Clinical Laboratories) ;
  • Kim, Young-Jin (Department of Bioanalysis, Seoul Medical Science Institute & Seoul Clinical Laboratories) ;
  • Lee, Sang-Hoo (Department of Bioanalysis, Seoul Medical Science Institute & Seoul Clinical Laboratories)
  • 권순호 ((재)서울의과학연구소 질량분석부) ;
  • 신혜진 ((재)서울의과학연구소 질량분석부) ;
  • 박지명 ((재)서울의과학연구소 질량분석부) ;
  • 이경률 ((재)서울의과학연구소 질량분석부) ;
  • 김영진 ((재)서울의과학연구소 질량분석부) ;
  • 이상후 ((재)서울의과학연구소 질량분석부)
  • Received : 2010.10.01
  • Accepted : 2011.03.03
  • Published : 2011.04.25
Download PDF
⟨ Previous Next ⟩

Abstract

The fragmentation patterns of a serine protease inhibitor, camostat, and its degradation product, 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA), were for the first time investigated by a triple quadrupole tandem mass spectrometry equipped with an electrospray source (ESI-MS/MS) in positive and/or negative ion mode under collision-induced dissociation (CID). The positive CID spectrum of camostat showed distinctly that the single bond (C-O) cleavage between carbonyl group and oxygen atom of the ester bonds of the compound favorably occurred and then the loss of N,N-dimethylcarbamoylmethyl group was more susceptible than that of guanidine moiety. In the positive ion CID spectrum of GBPA, the initial cleavage between the carbonyl group and oxygen atom of 4-guanidinobenzoyloxy group also occurred, yielding the most abundant fragment ion at m/z 145. On the other hand, the negative CID spectrum of GBPA characteristically showed the occurrence of the most abundant peak at m/z 226 resulting from the sequential neutral losses of $CO_2$ and HN=C=NH from the parent ion at m/z 312.

본 연구에서는 양성 및/또는 음성 이온 방식으로 저에너지 충돌-유발 분해(CID)를 이용한 serine protease 저해제인 camostat 와 그것의 분해산물인 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA)의 분해 패턴을 전자분무 소스가 있는 사중극자 텐덤 질량분석기(ESI-MS/MS)를 이용하여 최초로 조사하였다. Camostat의 양이온 CID 질량 스펙트럼 분석결과, 분자구조내 에스테르 결합을 이루는 카르보닐 기와 산소 원자사이의 단일 결합(C-O) 분해가 우선적으로 일어나고, guanidine 기의 초기 손실보다는 N,Ndimethylcarbamoylmethyl기의 초기 손실이 더 잘 일어난다는 것이 특징적으로 확인되었다. GBPA의 양이온 CID 스펙트럼의 경우는, 4-guanidinobenzoyloxy 기에 있는 카르보닐 기와 산소원자 사이의 초기 분해가 일어나서 m/z 145에서 가장 강도가 높은 피크를 만들었다. 반면에, GBPA의 음이온 스펙트럼은 m/z 312의 모분자 이온에서 $CO_2$와 NH=C=NH의 순차적인 중성 손실로 인하여 m/z 226의 가장 강도가 높은 피크가 특징적으로 생성되었다.

Keywords

References

  1. Y. Tamura, M. Hirado, K. Okamura, Y. Minato and S. Fujii, Biochim. Biophys. Acta, 484(2), 417-422(1977). https://doi.org/10.1016/0005-2744(77)90097-3
  2. N. Tanaka, R. Tsuchiya and K. Ishii, Adv. Exp. Med. Biol., 120B, 367-378(1979).
  3. S. Takasugi, H. Yonezawa, N. Ikei and T. Kanno, Digestion, 24(1), 36-41(1982). https://doi.org/10.1159/000198772
  4. M. Kanoh, H. Ibata, M. Miyagawa and Y. Matsuo, Biomed. Res., 10(suppl 1), 145-150(1989).
  5. M. Kitagawa, S. Naruse, H. Ishiguro and T. Hayakawa, Pancreas, 16(3), 427-431(1998). https://doi.org/10.1097/00006676-199804000-00035
  6. M. Sugiyama, Y. Atomi, N. Wada, A. Kuroda and T. Muto, J. Gastroenterol., 32(3), 374-379(1997). https://doi.org/10.1007/BF02934496
  7. I. Sasaki, Y. Suzuki, H. Naito, Y. Funayama, Y. Kamiyama, M. Takahashi, T. Matsuo, K. Fukushima, S. Matsuno and T. Sato, Biomed. Res., 10(suppl 1), 167-173(1989).
  8. I. Kobayashi, S. Ohwada, T. Ohya, T. Yokomori, H. Iesato and Y. Morishita, Hepatogastroenterology, 45(20), 558-562(1998).
  9. H. Sarles, Scan. J. Gastroenterol., 6(3), 193-198(1971). https://doi.org/10.3109/00365527109180692
  10. H. Sarles, Dig. Dis. Sci., 30(6), 573-574(1985). https://doi.org/10.1007/BF01320265
  11. M. Okuno, K. Akita, H. Moriwaki, N. Kawada, K. Ikeda, K. Kaneda, Y. Suzuki and S. Kojima, Gastroenterology, 120(7), 1784-1800(2001). https://doi.org/10.1053/gast.2001.24832
  12. J. Gibo, T. Ito, K. Kawabe, T. Hisano, M. Inoue, N. Fujimori, T. Oono, Y. Arita and H. Nawata, Lab. Invest., 85(1), 75-89(2005). https://doi.org/10.1038/labinvest.3700203
  13. K. Beckh, B. Goke, R. Muller and R. Arnold, Res. Exp. Med. (Berlin), 187(6), 401-406(1987). https://doi.org/10.1007/BF01852177
  14. T. Nishihata, Y. Saitoh and K. Sakai, Chem. Pharm. Bull. (Tokyo), 36(7), 2544-2550(1988). https://doi.org/10.1248/cpb.36.2544
  15. I. Midgley, A. J. Hood, P. Proctor, L. F. Chasseaud, S. R. Irons, K. N. Cheng, C. J. Brindley and R. Bonn, Xenobiotica, 24(1), 79-92(1994). https://doi.org/10.3109/00498259409043223
  16. X. Wang, Y. Sha, Z. Ge, W. Wang and R. Li. Rapid Commun. Mass Spectrom., 25, 349-354(2011). https://doi.org/10.1002/rcm.4847
  17. M. Hubert-Roux, F. Bounoure, M. Skiba, P. Bozec, F. Churlaud and C. M. Lange. J. Mass Spectrom., 45, 1121-1129(2010). https://doi.org/10.1002/jms.1790
  18. M. Marull and B. Rochat. J. Mass Spectrom., 41, 390-404(2006). https://doi.org/10.1002/jms.1002
  19. M.-Y. Zhang, N. Pace, E. H. Kerns, T. Kleintop, N. Kagan and T. Sakuma. J. Mass Spectrom., 40, 1017-1029(2005). https://doi.org/10.1002/jms.876
  20. X. Wang, Y. Sha and R. Li. Int. J. Mass Spectrom., 235, 111-115(2004). https://doi.org/10.1016/j.ijms.2004.03.012
  21. Z. Tozuka, H. Kaneko, T. Shiraga, Y. Mitani, M. Beppu, S. Terashita, A. Kawamura and A. Kagayama. J. Mass Spectrom., 38, 793-808(2003). https://doi.org/10.1002/jms.511
  22. H. Wang, Y. Wu and Z. Zhao. J. Mass Spectrom., 36, 58-70(2001). https://doi.org/10.1002/jms.104
  23. S. Kwon, W. Lee, H. Shin, S. Yoon, Y. Kim, Y. Kim, K. Lee and S. Lee. J. Mol. Struct., 938, 192-197(2009). https://doi.org/10.1016/j.molstruc.2009.09.025
  24. M. W. Forbes, R. A. Jockusch, A. B. Young and A. G. Harrison. J. Am. Soc. Mass Spectrom., 18, 1959-1966 (2007). https://doi.org/10.1016/j.jasms.2007.08.003
  25. P. M. Gehrig, P. E. Hunziker, S. Zahariev and S. pongor. J. Am. Soc. Mass Spectrom., 15, 142-149(2004). https://doi.org/10.1016/j.jasms.2003.10.002