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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳珮珊(Pai-Shan Chen) | |
dc.contributor.author | Yi-Hung Chou | en |
dc.contributor.author | 周奕宏 | zh_TW |
dc.date.accessioned | 2021-06-17T02:00:38Z | - |
dc.date.available | 2027-07-19 | |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-19 | |
dc.identifier.citation | 1. UNODC, New psychoactive substances. 2016.
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WHO, Ethylone critical review report. Expert Committee on Drug Dependence Thirty-eighth Meeting 2016, Agenda item 4.5. 9. Administration, U. D. E., National Forensic Laboratory Information System (NFLIS): 2015 annual report. 2015. 10. Lee, S.-F.; Hsu, J.; Tsay, W.-I., The trend of drug abuse in Taiwan during the years 1999 to 2011. Journal of Food and Drug Analysis 2013, 21 (4), 390-396. 11. 衛生福利部, 藥物濫用案件暨檢驗統計資料 [105年報分析]. 2016. 12. Hsiu-Chuan Liu; Yun-Chen Tsao; Ray H.Liu; Lin, D.-L., New Psychoactive Substances (NPS)-Related Deaths in Taiwan: A Report on the Analysis of Postmortem Blood Specimens from 87 Fatality Cases in 2015. Toxicology, D. o. F., Ed. 2015. 13. Simmler, L. D.; Buser, T. A.; Donzelli, M.; Schramm, Y.; Dieu, L. H.; Huwyler, J.; Chaboz, S.; Hoener, M. C.; Liechti, M. E., Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 2013, 168 (2), 458-70. 14. Mueller, D. M.; Rentsch, K. M., Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS(n), and metabolism of 11 cathinones. Anal Bioanal Chem 2012, 402 (6), 2141-51. 15. Pedersen, A. J.; Petersen, T. H.; Linnet, K., In vitro metabolism and pharmacokinetic studies on methylone. Drug Metab Dispos 2013, 41 (6), 1247-55. 16. Zaitsu, K.; Katagi, M.; Tatsuno, M.; Sato, T.; Tsuchihashi, H.; Suzuki, K., Recently abused β-keto derivatives of 3,4-methylenedioxyphenylalkylamines: a review of their metabolisms and toxicological analysis. Forensic Toxicology 2011, 29 (2), 73-84. 17. Kamata, H. T.; Shima, N.; Zaitsu, K.; Kamata, T.; Miki, A.; Nishikawa, M.; Katagi, M.; Tsuchihashi, H., Metabolism of the recently encountered designer drug, methylone, in humans and rats. Xenobiotica 2006, 36 (8), 709-23. 18. Zaitsu, K.; Katagi, M.; Kamata, H. T.; Kamata, T.; Shima, N.; Miki, A.; Tsuchihashi, H.; Mori, Y., Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. Forensic Sci Int 2009, 188 (1-3), 131-9. 19. Lopez-Arnau, R.; Martinez-Clemente, J.; Carbo, M.; Pubill, D.; Escubedo, E.; Camarasa, J., An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'. Prog Neuropsychopharmacol Biol Psychiatry 2013, 45, 64-72. 20. Uralets, V.; Rana, S.; Morgan, S.; Ross, W., Testing for designer stimulants: metabolic profiles of 16 synthetic cathinones excreted free in human urine. J Anal Toxicol 2014, 38 (5), 233-41. 21. Casarett, L. J., Doull, J., & Klaassen, C. D., Casarett and Doull's toxicology: The basic science of poisons 8ed.; McGraw-Hill.: New York, 2013. 22. David Josephy, P.; Peter Guengerich, F.; Miners, J. O., 'Phase I and Phase II' drug metabolism: terminology that we should phase out? Drug metabolism reviews 2005, 37 (4), 575-80. 23. Jia, L.; Liu, X., The conduct of drug metabolism studies considered good practice (II): in vitro experiments. Curr Drug Metab 2007, 8 (8), 822-9. 24. Yao, M.; Ma, L.; Humphreys, W. G.; Zhu, M., Rapid screening and characterization of drug metabolites using a multiple ion monitoring-dependent MS/MS acquisition method on a hybrid triple quadrupole-linear ion trap mass spectrometer. J Mass Spectrom 2008, 43 (10), 1364-75. 25. Zhu, M. S. L. M., Mass Spectrometry in Drug Metabolism and Disposition: Basic Principles and Applications. 1 ed.; John Wiley: Hoboken, NJ, 2011. 26. Hoffmann, E. d.; Stroobant, V., Mass spectrometry : principles and applications. 3rd ed.; J. Wiley: Chichester, West Sussex, England ; Hoboken, NJ, 2007; p xii, 489 p. 27. Fornal, E., Identification of substituted cathinones: 3,4-Methylenedioxy derivatives by high performance liquid chromatography-quadrupole time of flight mass spectrometry. J Pharm Biomed Anal 2013, 81-82, 13-9. 28. Fornal, E., Formation of odd-electron product ions in collision-induced fragmentation of electrospray-generated protonated cathinone derivatives: aryl alpha-primary amino ketones. Rapid Commun Mass Spectrom 2013, 27 (16), 1858-66. 29. Fornal, E., Study of collision-induced dissociation of electrospray-generated protonated cathinones. Drug Test Anal 2014, 6 (7-8), 705-15. 30. Strano Rossi, S.; Odoardi, S.; Gregori, A.; Peluso, G.; Ripani, L.; Ortar, G.; Serpelloni, G.; Romolo, F. S., An analytical approach to the forensic identification of different classes of new psychoactive substances (NPSs) in seized materials. Rapid Commun Mass Spectrom 2014, 28 (17), 1904-16. 31. Reitzel, L. A.; Dalsgaard, P. W.; Muller, I. B.; Cornett, C., Identification of ten new designer drugs by GC-MS, UPLC-QTOF-MS, and NMR as part of a police investigation of a Danish internet company. Drug Test Anal 2012, 4 (5), 342-54. 32. Ellefsen, K. N.; Concheiro, M.; Suzuki, M.; Rice, K. C.; Elmore, J. S.; Baumann, M. H.; Huestis, M. A., Quantification of methylone and metabolites in rat and human plasma by liquid chromatography-tandem mass spectrometry. Forensic Toxicology 2015, 33 (2), 202-212. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67959 | - |
dc.description.abstract | 合成卡西酮為台灣目前最常被檢出的新興濫用物質,而3,4-亞甲基雙氧甲基卡西酮及3,4-亞甲基雙氧-N-乙基卡西酮為常見的其中二種。由於這二種物質的研究在各領域如臨床,藥理,法醫等領域皆相當缺乏,限制了治療與檢測上的發展。過去的文獻指出3,4-亞甲基雙氧甲基卡西酮及3,4-亞甲基雙氧-N-乙基卡西酮分別能透過五種代謝途徑形成七種代謝產物。本研究利用人類肝細胞成分模擬人體代謝反應,並利用精確質量與碎片模式,分別在3,4-亞甲基雙氧甲基卡西酮及3,4-亞甲基雙氧-N-乙基卡西酮偵測到其中五種來自於一期代謝路徑的產物,其中二種為共同產物;此外,其中一共同產物3,4-亞甲基雙氧去甲麻黃鹼,首次在液相層析質譜被偵測到。而二期代謝物的部分皆沒有被偵測到。在時序研究的探討中發現,羥基化之代謝產物和共同代謝產物3,4-亞甲基雙氧去甲麻黃鹼,前者於四十八小時後會無法被偵測到,後者則在十二小時後有轉換率上升的現象,有能夠成為評估個體是否有近期使用3,4-亞甲基雙氧甲基卡西酮或3,4-亞甲基雙氧-N-乙基卡西酮之潛力,但須有更多研究以證實其實用性。 | zh_TW |
dc.description.abstract | Synthetic cathinones are the most prevalent new psychoactive substances (NPS) in Taiwan. Methylone and ethylone are two of them. Since the research in clinical and forensic field are lacking, the development of treatment, detection and investigation are restricted. In the literature review, methylone and ethylone each formed 7 metabolites through 5 metabolic pathways. In this study, the phase I and phase II metabolites of methylone and ethylone were synthesized in vitro by human liver microsome and cyotosol. We utilized the accurate masses and fragmentation patterns to observe the metabolites. Total 8 metabolites were confirmed as previously suspected, with 6 unique and 2 common metabolites. In addition, one of the common metabolite 3’,4’-methylenedioxy-cathine was the first time detected in LC-MS. The phase II metabolites were not detected. In the discussion of time course experiments, the hydroxylated metabolites and 3’,4’-methylenedioxycathine, which the former could not be detected after 48 hours of phase I reaction and the later revealed increased metabolic rate after 12 hours. Therefore, these 2 metabolites may become potential markers that can indicate recent abuse of methylone and ethylone. But further researches should be conducted to prove the hypothesis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T02:00:38Z (GMT). No. of bitstreams: 1 ntu-106-R01452004-1.pdf: 5405382 bytes, checksum: 40a29cf63c11c84caff871eb01c3321c (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 中文摘要 iii
Abstract iv Contents v Figures vii Table ix Equation ix Terminology x Chapter 1 Introduction 1 1.1 Background of methylone and ethylone 1 1.2 Motivation 4 1.3 Literature review 5 1.4 Mass spectrometry and metabolite identification 9 1.5 Identification of metabolites by fragmentation pattern using triple quadrupole MS and HRMS 10 1.6 Establish the MRM transitions for metabolites 11 1.7 Objectives and aims 12 Chapter 2 Materials and Methods 13 2.1 Materials 13 2.2 Equipment 13 LC-MS 13 LC-HRMS 15 Infusion 15 Other equipment 16 2.3 In vitro synthesis of phase I and phase II metabolites 16 Chapter 3 Results and Discussion 19 3.1 Detection of in vitro metabolites by triple quadrupole MS 19 3.2 Identification of the in vitro phase I metabolites 21 3.2.1 General fragmentation pattern of methylone and ethylone 22 3.2.2 Phase I metabolites of methylone 23 3.2.3 Phase I metabolites of ethylone 45 3.2.4 HR-MS and HR-MS/MS spectra of the phase I metabolites 59 3.2.5 MRM transition, productivity and metabolic trend of phase I metabolites 60 Chapter 4 Conclusion 65 Acknowledgement 66 References 67 Supplementary data 70 | |
dc.language.iso | zh-TW | |
dc.title | "以人類肝臟細胞微小體及細胞質體建立3,4-亞甲基雙氧甲基卡西酮和3,4-亞甲基雙氧-N-乙基卡西酮之代謝物" | zh_TW |
dc.title | Establish the metabolic profiles of methylone and ethylone using human liver microsome and cytosol | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 王勝盟(Sheng-Meng Wang),陳家揚(Chia-Yang Chen) | |
dc.subject.keyword | 3,4-亞甲基雙氧甲基卡西酮,3,4-亞甲基雙氧-N-乙基卡西酮,體外代謝反應,液相層析串聯質譜,高解析質譜,代謝物鑑定, | zh_TW |
dc.subject.keyword | Methylone,ethylone,in vitro metabolism,liquid chromatography-tandem mass spectrometry,liquid chromatography-HRMS,metabolite identification, | en |
dc.relation.page | 86 | |
dc.identifier.doi | 10.6342/NTU201701719 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-07-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 法醫學研究所 | zh_TW |
顯示於系所單位: | 法醫學科所 |
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