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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 毒理學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59656
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor陳惠文(Huei-Wen Chen)
dc.contributor.authorHsin-Tung Liuen
dc.contributor.author劉芯彤zh_TW
dc.date.accessioned2021-06-16T09:31:48Z-
dc.date.available2022-02-24
dc.date.copyright2017-02-24
dc.date.issued2017
dc.date.submitted2017-02-15
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2. Svatos, A., Mass spectrometric imaging of small molecules. Trends Biotechnol 2010, 28 (8), 425-434.
3. Pozebon, D.; Scheffler, G. L.; Dressler, V. L.; Nunes, M. A. G., Review of the applications of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to the analysis of biological samples. J Anal Atom Spectrom 2014, 29 (12), 2204-2228.
4. Piehowski, P. D.; Petyuk, V. A.; Orton, D. J.; Xie, F.; Moore, R. J.; Ramirez-Restrepo, M.; Engel, A.; Lieberman, A. P.; Albin, R. L.; Camp, D. G.; Smith, R. D.; Myers, A. J., Sources of Technical Variability in Quantitative LC-MS Proteomics: Human Brain Tissue Sample Analysis. J Proteome Res 2013, 12 (5), 2128-2137.
5. Deeb, S.; McKeown, D. A.; Torrance, H. J.; Wylie, F. M.; Logan, B. K.; Scott, K. S., Simultaneous Analysis of 22 Antiepileptic Drugs in Postmortem Blood, Serum and Plasma Using LC-MS-MS with a Focus on Their Role in Forensic Cases. J Anal Toxicol 2014, 38 (8), 485-494.
6. Larkin, S. E.; Johnston, H. E.; Jackson, T. R.; Jamieson, D. G.; Roumeliotis, T. I.; Mockridge, C. I.; Michael, A.; Manousopoulou, A.; Papachristou, E. K.; Brown, M. D.; Clarke, N. W.; Pandha, H.; Aukim-Hastie, C. L.; Cragg, M. S.; Garbis, S. D.; Townsend, P. A., Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study. Br J Cancer 2016, 115 (9), 1078-1086.
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9. Zhang, T. J.; Chen, S. L.; Syed, I.; Stahlman, M.; Kolar, M. J.; Homan, E. A.; Chu, Q.; Smith, U.; Boren, J.; Kahn, B. B.; Saghatelian, A., A LC-MS-based workflow for measurement of branched fatty acid esters of hydroxy fatty acids. Nat Protoc 2016, 11 (4), 747-763.
10. Desmet, G.; Eeltink, S., Fundamentals for LC Miniaturization. Anal Chem 2013, 85 (2), 543-556.
11. Jandera, P.; Blomberg, L. G.; Lundanes, E., Controlling the retention in capillary LC with solvents, temperature, and electric fields. J Sep Sci 2004, 27 (17-18), 1402-1418.
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13. Bereman, M. S.; Hsieh, E. J.; Corso, T. N.; Van Pelt, C. K.; Maccoss, M. J., Development and characterization of a novel plug and play liquid chromatography-mass spectrometry (LC-MS) source that automates connections between the capillary trap, column, and emitter. Mol Cell Proteomics 2013, 12 (6), 1701-8.
14. Hilhorst, M.; Briscoe, C.; van de Merbel, N., Sense and nonsense of miniaturized LC-MS/MS for bioanalysis. Bioanalysis 2014, 6 (24), 3263-3265.
15. Tan, F.; Chen, S. O.; Zhang, Y. J.; Cai, Y.; Qian, X. H., A simple and efficient frit preparation method for one-end tapered-fused silica-packed capillary columns in nano-LC-ESI MS. Proteomics 2010, 10 (8), 1724-1727.
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31. Antonopoulou, G.; Kirkou, A.; Stasinakis, A. S., Quantitative and qualitative greywater characterization in Greek households and investigation of their treatment using physicochemical methods. Sci Total Environ 2013, 454-455, 426-32.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59656-
dc.description.abstract液相層析串聯質譜儀分析廣泛地被應用於諸多領域,在法醫學或生物領域中,奈米級液相層析質譜分析技術相對傳統液相層析又有高靈敏及樣品量需求少等優點,本篇研究欲將其應用於法醫毒理以偵測66種常見濫用藥物、其相關代謝物以及海洛因不純物-acetylthebaine之一級、二級代謝物。然而,分析物含括極性及非極性特性,難以同時使用一種層析管柱進行偵測,因此,本篇研究欲混和兩種固定相於一體以改善此缺點。首先,篩選七種固定相並以Hypersil gold C18及Porous graphite carbon (PGC) 作為最終兩混和材質,接著,嘗試以不同比例及混和方式比較分析物峰形及峰寬,並選擇1P9HG混和型層析管柱有較好之表現。然而,由於PGC的特殊性,一些分析物於最佳化時無法被偵測,推測可能因其有活性碳相似之性質導致分析物吸附,嘗試調整沖提液溫度及游離源電壓,同時評估分析物出現數目,最終發現仍有兩藥物消失(JWH-018 及acetylthebaol) 。排除此現象,整體而言1P9HG混和型層析管柱有最好之結果,期望未來能針對量少且極性程度差異大的樣品有實務上的應用。zh_TW
dc.description.abstractLiquid chromatography coupling to mass spectrometry is widely used in several areas. In the forensic science or biological area, it is sometimes quite challenging for the detection of compounds in limited amount samples. The miniaturized Nano-LC present as a great choice for compensating this issue. Sixty-six drugs and phase I, II metabolites of acetylthebaine from heroin impurities were selected as our target analytes. A wide range of polarities are included which is quite difficult in detection within one sample shot due to the analytical column limited selection properties. In order to solve the problem, we tried to combine two materials with different properties out of seven columns. Hypersil gold C18 and Porous graphite carbon (PGC) were selected as our final mixing candidates. Several parameters had been evaluated, including mixing ratios and mixing fashions, by comparing analytes’ peak shape and peak width. The final pre-mixing 1P9HG column was selected with good performance to most compounds except for the disappearance for two compounds. Temperature and ion source voltage modulation had been tested, however still, missing in two analytes (JWH-018 and acetylthebaol). Besides the phenomenon, it may be useful in detection of a wide range polarities samples in limited amount.en
dc.description.provenanceMade available in DSpace on 2021-06-16T09:31:48Z (GMT). No. of bitstreams: 1
ntu-106-R03447005-1.pdf: 5530016 bytes, checksum: 028beef335a78e2b9faba0748abfa587 (MD5)
Previous issue date: 2017
en
dc.description.tableofcontents誌謝 II
中文摘要 III
Abstract IV
Contents V
List of figures VII
List of Tables IX
Chapter 1 Introduction 1
1.1 The application of liquid chromatography-mass spectrometry (LC-MS) 1
1.2 LC-MS introduction 3
1.2.1 Mass spectrometry 3
1.2.2 Ionization source – Electrospray ionization (ESI) 3
1.2.3 Mass analyzer-Tandem Mass Spectrometry (MS/MS) with Triple Quadrupole Mass Spectrometer 6
1.2.4 Liquid chromatography 11
1.3 Nanoscale liquid chromatography (Nano-LC) 13
1.4 Introduction of Nano-LC 14
1.5 Social problems caused by drug abuse 16
1.5.1 Heroin abuse 17
1.6 Aims, hypothesis and objectives 23
1.6.1 Aims 23
1.6.2 Hypothesis 23
1.6.3 Objectives 26
Chapter 2 Materials and Methods 27
2.1 Equipment 27
2.2 Materials 27
2.3 Chemicals and reagents 28
2.4 In vitro synthesis of phase I and phase II metabolites 30
2.4.1 Conduction of Phase I reaction 30
2.4.2 Conduction of glucuronide-conjugation 30
2.4.3 Conduction of sulfonate-conjugation 31
2.5 Emitter tip construction 31
2.6 Packing analytical column 31
2.7 Nano-liquid chromatography-Mass spectrometry (Nano-LC-MS) 34
2.8 Data acquisition 35
2.9 Stocking solution and working solution preparation 35
2.10 Column selection 35
2.11 Combination of both polar and nonpolar materials 37
2.12 Conduction of the pre-mixing column 37
2.13 Conduction of the reverse-packing column 37
2.14 Temperature control 38
2.15 Test for ion source voltage 38
Chapter 3 Result and Discussion 39
3.1 In vitro synthesis of phase I and phase II metabolites 39
3.1.1 Phase I reaction 39
3.1.2 Phase II reaction 40
3.2 Column selection 43
3.2.1 Properties of seven candidate columns 43
3.2.2 Column selection 44
3.3 Detection of heroin biomarkers in PGC column 60
3.4 Combination of both polar and nonpolar materials 61
3.5 Conduction of the pre-mixing column 65
3.6 Conduction of the reverse-packing column 67
3.7 Temperature control 70
3.8 Test for different ion source voltage 73
3.9 Retention effect between PGC and target analytes 76
3.10 The disappearance of analytes 78
3.11 Column validation 81
3.12 Calibration curve 84
Appendix 86
References 127
dc.language.isoen
dc.subjectPGC層析管柱zh_TW
dc.subject濫用藥物zh_TW
dc.subject雙材料混和型層析管柱zh_TW
dc.subject法醫毒理學zh_TW
dc.subject法醫毒理學zh_TW
dc.subject雙材料混和型層析管柱zh_TW
dc.subject濫用藥物zh_TW
dc.subjectPGC層析管柱zh_TW
dc.subjectHypersil gold C18 層析管柱zh_TW
dc.subject奈米級液相層析串聯質譜分析zh_TW
dc.subject奈米級液相層析串聯質譜分析zh_TW
dc.subjectHypersil gold C18 層析管柱zh_TW
dc.subjectNano liquid chromatography-tandem mass spectrometryen
dc.subjecthypersil gold C18en
dc.subjectporous graphite carbon (PGC)en
dc.subjectillicit drugsen
dc.subjectbimaterial hybridized columnen
dc.subjectforensic toxicologyen
dc.subjectNano liquid chromatography-tandem mass spectrometryen
dc.subjecthypersil gold C18en
dc.subjectporous graphite carbon (PGC)en
dc.subjectillicit drugsen
dc.subjectbimaterial hybridized columnen
dc.subjectforensic toxicologyen
dc.title利用雙材料混和型層析管柱串聯奈米級液相層析質譜儀同時偵測極性與非極性濫用藥物zh_TW
dc.titleImproved simultaneous detection of polar and nonpolar drugs by bimaterial hybridized column on nanoLC-MS/MS systemen
dc.typeThesis
dc.date.schoolyear105-1
dc.description.degree碩士
dc.contributor.coadvisor陳珮珊(Pai-Shan Chen)
dc.contributor.oralexamcommittee黃賢達,陳家揚
dc.subject.keyword奈米級液相層析串聯質譜分析,Hypersil gold C18 層析管柱,PGC層析管柱,濫用藥物,雙材料混和型層析管柱,法醫毒理學,zh_TW
dc.subject.keywordNano liquid chromatography-tandem mass spectrometry,hypersil gold C18,porous graphite carbon (PGC),illicit drugs,bimaterial hybridized column,forensic toxicology,en
dc.relation.page128
dc.identifier.doi10.6342/NTU201700506
dc.rights.note有償授權
dc.date.accepted2017-02-15
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept毒理學研究所zh_TW
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