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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳珮珊(Pai-Shan Chen) | |
| dc.contributor.author | I-Lin Tsai | en |
| dc.contributor.author | 蔡易霖 | zh_TW |
| dc.date.accessioned | 2021-06-17T07:31:16Z | - |
| dc.date.available | 2024-08-26 | |
| dc.date.copyright | 2019-08-26 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-06-10 | |
| dc.identifier.citation | 1. UNODC. New psychoactive substances. 2018.
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Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem. 2010, 397, 1225-33. 29. Prakash, C., C. L. Shaffer, and A. Nedderman. Analytical strategies for identifying drug metabolites. Mass Spectrom Rev. 2007, 26, 340-69. 30. Liu, L. J. X. The conduct of drug metabolism studies considered good practice (II) in vitro experiments. Curr Drug Metab. 2007, 8(8), 822–829. 31. Li, A. P. Preclinical in vitro screening assays for drug-like properties. Drug Discov Today Technol. 2005, 2, 179-85. 32. Asha, S. and M. Vidyavathi. Role of human liver microsomes in in vitro metabolism of drugs-a review. Appl Biochem Biotechnol. 2010, 160, 1699-722. 33. Liu, X. and L. Jia. The conduct of drug metabolism studies considered good practice (I) analytical systems and in vivo studies. Curr Drug Metab. 2007, 8, 815-821. 34. Yao, M., L. Ma, W. G. Humphreys, and M. Zhu. 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, 1364-75. 35. Stroobant, E. d. H. V. Ch.6 Analytical information. Mass spectrometry: principles and applications. 2007, 3rd edition, 247. 36. Ellefsen, K. N., M. Concheiro, M. Suzuki, K. C. Rice, J. S. Elmore, M. H. Baumann, and M. A. Huestis. Quantification of methylone and metabolites in rat and human plasma by liquid chromatography-tandem mass spectrometry. Forensic Toxicol. 2015, 33, 202-212. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73375 | - |
| dc.description.abstract | 合成卡西酮是台灣目前最常被檢出的新興濫用藥物，分別於2012以及2016年被列為第三級管制藥品的3,4-亞甲基雙氧甲基卡西酮與3,4-亞甲基雙氧-N-乙基卡西酮為最常見的兩種合成卡西酮衍生物。為了尋找兩種物質在人類檢體中的檢測生物指標，了解這兩種物質的代謝是非常重要。然而目前對於這兩種物質的代謝研究，尤其針對二級代謝物的部分仍很有限。過去的研究指出3,4-亞甲基雙氧甲基卡西酮與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，並在液相層析質譜儀以及液相層析高解析質譜儀上，藉由碎片圖譜與精確質量鑑定其代謝產物，總共偵測到八種一級代謝產物以及三種二級代謝產物，其中的三種二級代謝產物DHMC-S、DHEC-S、DHEC-G為首次被合成出來。依此結果建立檢測方法分析已知為3,4-亞甲基雙氧甲基卡西酮與3,4-亞甲基雙氧-N-乙基卡西酮使用者尿液檢體中的代謝物組成，發現dihydromethylone與3-hydroxy-4-methoxymeth-cathinone (3-OH-4-MeO-MC-G)及其異構物4-hydroxy-3-methoxymeth-cathinone (4-OH-3-MeO-MC-G)其中之一為3,4-亞甲基雙氧甲基卡西酮使用者尿液中主要代謝物；dihydroethylone與DHEC-S為3,4-亞甲基雙氧-N-乙基卡西酮使用者尿液中主要代謝物，但須有更多尿液樣本讓代謝趨勢更加明確。 | zh_TW |
| dc.description.abstract | Synthetic cathinone is the most frequently abused new psychoactive substances (NPS) in Taiwan. Methylone and ethylone, which were categorized as scheduled III drug in 2012 and 2016 in Taiwan, are two derivatives of synthetic cathinone. It is important to investigate the metabolism of methylone and ethylone in order to find specific markers in human specimen. However, the metabolic profile of these two compounds are still limited especially for phase II metabolites. In previous study, methylone and ethylone each formed 7 metabolites through 5 metabolic pathways. In this study, we in vitro synthesized phase I and phase II metabolites by human liver microsomes and cytosols, and observed metabolites by fragment pattern and accurate mass using liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). Total eight phase I metabolites and three phase II metabolites were detected. Three in vitro phase II metabolites, sulfate conjugate of dihydroxymethcathinone (DHMC-S) from methylone, sulfate conjugate of dihydroxyethcathinone (DHEC-S) from ethylone and glucuronide conjugate of dihydroxymethcathinone (DHEC-G) from ethylone have never reported before. The method was established to identify the metabolites in human specimens. Urine samples from methylone and ethylone abusers were analyzed to evaluate the composition of metabolites. Dihydromethylone and glucuronide conjugate of 3-hydroxy-4-methoxymeth-cathinone (3-OH-4-MeO-MC-G) or its isomer 4-OH-3-MeO-MC-G were major metabolites of methylone, and Dihydroethylone and DHEC-S were major metabolites of ethylone in abusers urine samples. But more urine sample should be analyzed to make the metabolic trend more obvious. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T07:31:16Z (GMT). No. of bitstreams: 1 ntu-108-R03452003-1.pdf: 4143903 bytes, checksum: 8ac6c4dfc487ffe04e042dde7614c282 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 國立臺灣大學碩士學位論文 口試委員會審定書 i
謝辭 ii 中文摘要 iii Abstract iv Contents vi Figures viii Tables x Equations x Terminology xi Chapter 1 Introduction 1 1.1 Background of methylone and ethylone 1 1.2 Metabolism of methylone and ethylone 4 1.3 Phase I and phase II metabolism 6 1.4 Mass spectrometry and metabolite identification 8 1.5 Establish the MRM transitions for metabolites 9 1.6 Objectives and aims 10 Chapter 2 Materials and Methods 13 2.1 Materials 13 2.2 Equipment 14 2.3 In vitro synthesis of phase I and phase II metabolites 15 2.4 Urine sample collection and preparation 17 2.5 Method validation 18 Chapter 3. Results and Discussion 20 3.1 In vitro phase I metabolic profile of methylone and ethylone 20 3.1.1 Phase I metabolites of methylone 20 3.1.2 Phase I metabolites of ethylone 25 3.1.3 Metabolic trend of phase I metabolites of methylone and ethylone 26 3.2 In vitro phase II metabolic profile of methylone and ethylone 28 3.2.1 In vitro phase II biosynthesis of glucuronide conjugation from phase I metabolites of ethylone 29 3.2.2 In vitro phase II biosynthesis of sulfate conjugation from phase I metabolites of methylone 32 3.2.3 In vitro phase II biosynthesis of sulfate conjugation from phase I metabolites of ethylone 33 3.3 In vivo phase II metabolic profile of methylone and ethylone 38 3.3.1 In vivo glucuronide-conjugated metabolites of methylone and ethylone in human urine 38 3.3.2 In vivo sulfate-conjugated metabolites of methylone and ethylone in human urine 47 3.4 Method validation 55 3.5 The detection of metabolites in human urine from abusers of methylone and ethylone 58 3.5.1 Metabolites of methylone in human urine and comparison of in vitro and in vivo metabolites 58 3.5.2 Metabolites of ethylone in human urine and comparison of in vitro and in vivo metabolites 62 3.5.3 Comparison the metabolites of methylone and ethylone in human urine 65 Chapter 4 Conclusions 67 Reference 69 | |
| dc.language.iso | en | |
| dc.title | "利用人類肝臟細胞微小體及尿液鑑定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 | Identify the metabolites of methylone and ethylone using human liver microsomes and human urine | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃賢達(Shang-Da Huang),李茂榮(Maw-Rong Lee),陳亮妤(Lian-Yu Chen),廖尉斯(Wei-Ssu Liao) | |
| dc.subject.keyword | 合成卡西酮,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,液相層析質譜儀,液相層析高解析質譜儀,體外代謝反應,代謝物鑑定, | zh_TW |
| dc.subject.keyword | Synthetic cathinones,methylone,ethylone,liquid chromatography-tandem mass spectrometry,liquid chromatography-high resolution mass spectrometry,in vitro metabolism,metabolite identification, | en |
| dc.relation.page | 71 | |
| dc.identifier.doi | 10.6342/NTU201900886 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-06-11 | |
| 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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