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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 法醫學科所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94741
完整後設資料紀錄
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dc.contributor.advisor陳冠元zh_TW
dc.contributor.advisorGuan-Yuan Chenen
dc.contributor.author李俐融zh_TW
dc.contributor.authorLi-Jung Lien
dc.date.accessioned2024-08-16T17:55:28Z-
dc.date.available2024-08-17-
dc.date.copyright2024-08-16-
dc.date.issued2024-
dc.date.submitted2024-06-24-
dc.identifier.citation1. Heal, D.J., S.L. Smith, J. Gosden, and D.J. Nutt, Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol, 2013. 27(6): p. 479-96.
2. Crosby, M.M. and K.A. Moore, Amphetamines/Sympathomimetic Amines, in Principles of Forensic Toxicology, B.S. Levine and S. Kerrigan, Editors. 2020, Springer International Publishing: Cham. p. 449-466.
3. Dragan, A.-M., et al., Analytical techniques for the detection of amphetamine-type substances in different matrices: A comprehensive review. TrAC Trends in Analytical Chemistry, 2021. 145: p. 116447.
4. Kaye, S., R. McKetin, J. Duflou, and S. Darke, Methamphetamine and cardiovascular pathology: a review of the evidence. Addiction, 2007. 102(8): p. 1204-11.
5. Bowyer, J.F. and J.P. Hanig, Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity. Temperature (Austin), 2014. 1(3): p. 172-82.
6. Tsatsakis, A.M., et al., A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse. Journal of Clinical Medicine, 2019. 8.
7. Åhman, A., et al., Mortality and causes of death among people who inject amphetamine: A long-term follow-up cohort study from a needle exchange program in Sweden. Drug and Alcohol Dependence, 2018. 188: p. 274-280.
8. Rasmussen, N., Amphetamine-Type Stimulants: The Early History of Their Medical and Non-Medical Uses. Int Rev Neurobiol, 2015. 120: p. 9-25.
9. Paz-Ramos, M.I., S.L. Cruz, and V. Violante-Soria, Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns. Rev Invest Clin, 2023. 75(3): p. 143-157.
10. Chen, J.Y., et al., Development of an analytical method to detect simultaneously 219 new psychoactive substances and 65 other substances in urine specimens using LC-QqQ MS/MS with CriticalPairFinder and TransitionFinder. Talanta, 2022. 238(Pt 1): p. 122979.
11. Chen, J.Y., et al., Defective determination of synthetic cathinones in blood for forensic investigation. Clin Chim Acta, 2023. 539: p. 122-129.
12. Miyaguchi, H., et al., Development of a micropulverized extraction method for rapid toxicological analysis of methamphetamine in hair. J Chromatogr A, 2007. 1163(1-2): p. 43-8.
13. Wennig, R., Potential problems with the interpretation of hair analysis results. Forensic Science International, 2000. 107(1): p. 5-12.
14. Usman, M., et al., Forensic toxicological analysis of hair: a review. Egyptian Journal of Forensic Sciences, 2019. 9(1): p. 17.
15. Zhuo, Y., et al., Simultaneous Quantitative Determination of Amphetamines, Opiates, Ketamine, Cocaine and Metabolites in Human Hair: Application to Forensic Cases of Drug Abuse. Journal of Forensic Sciences, 2020. 65(2): p. 563-569.
16. Meng, L., Y. Dai, C. Chen, and J. Zhang, Determination of amphetamines, ketamine and their metabolites in hair with high-speed grinding and solid-phase microextraction followed by LC-MS. Forensic Sci Res, 2021. 6(3): p. 273-280.
17. Wu, Y.H., K.L. Lin, S.C. Chen, and Y.Z. Chang, Simultaneous quantitative determination of amphetamines, ketamine, opiates and metabolites in human hair by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom, 2008. 22(6): p. 887-97.
18. Miyaguchi, H. and H. Inoue, Determination of amphetamine-type stimulants, cocaine and ketamine in human hair by liquid chromatography/linear ion trap-Orbitrap hybrid mass spectrometry. Analyst, 2011. 136(17): p. 3503-11.
19. Mantinieks, D., P. Wright, M. Di Rago, and D. Gerostamoulos, A systematic investigation of forensic hair decontamination procedures and their limitations. Drug Test Anal, 2019. 11(10): p. 1542-1555.
20. Cooper, G.A., R. Kronstrand, and P. Kintz, Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int, 2012. 218(1-3): p. 20-4.
21. Cairns, T., V. Hill, M. Schaffer, and W. Thistle, Removing and identifying drug contamination in the analysis of human hair. Forensic Sci Int, 2004. 145(2-3): p. 97-108.
22. Ropero-Miller, J.D., M.A. Huestis, and P.R. Stout, Cocaine analytes in human hair: evaluation of concentration ratios in different cocaine sources, drug-user populations and surface-contaminated specimens. J Anal Toxicol, 2012. 36(6): p. 390-8.
23. Chagas, A., et al., Particle-size distribution (PSD) of pulverized hair: A quantitative approach of milling efficiency and its correlation with drug extraction efficiency. Forensic Sci Int, 2017. 277: p. 188-196.
24. Burgueño, M.J., A. Alonso, and S. Sánchez, Amphetamines and cannabinoids testing in hair: Evaluation of results from a two-year period. Forensic Sci Int, 2016. 265: p. 47-53.
25. Salomone, A., et al., Determination of cathinones and other stimulant, psychedelic, and dissociative designer drugs in real hair samples. Anal Bioanal Chem, 2016. 408(8): p. 2035-42.
26. Imbert, L., et al., Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites. Forensic Sci Int, 2014. 234: p. 132-8.
27. Lendoiro, E., et al., An LC-MS/MS methodological approach to the analysis of hair for amphetamine-type-stimulant (ATS) drugs, including selected synthetic cathinones and piperazines. Drug Test Anal, 2017. 9(1): p. 96-105.
28. Niebel, A., et al., Detection and quantification of synthetic cathinones and selected piperazines in hair by LC-MS/MS. Forensic Sci Med Pathol, 2020. 16(1): p. 32-42.
29. Qi, B.-L., et al., Derivatization for liquid chromatography-mass spectrometry. TrAC Trends in Analytical Chemistry, 2014. 59: p. 121-132.
30. Chen, H.C., P.D. Lee, and Y.Z. Chang, Development of a rapid and sensitive LC-MS/MS assay for the quantification of commonly abused drugs in Asia in a micro-segment of a single hair using microwave-assisted extraction and dansyl chloride derivatization. J Pharm Biomed Anal, 2022. 213: p. 114678.
31. Zhao, S., et al., Metabolomic Coverage of Chemical-Group-Submetabolome Analysis: Group Classification and Four-Channel Chemical Isotope Labeling LC-MS. Anal Chem, 2019. 91(18): p. 12108-12115.
32. Yu, X., L. Yu, F. Ma, and P. Li, Quantification of phenolic compounds in vegetable oils by mixed-mode solid-phase extraction isotope chemical labeling coupled with UHPLC-MS/MS. Food Chem, 2021. 334: p. 127572.
33. Chen, G.Y. and Q. Zhang, Simultaneous quantification of free fatty acids and acylcarnitines in plasma samples using dansylhydrazine labeling and liquid chromatography-triple quadrupole mass spectrometry. Anal Bioanal Chem, 2020. 412(12): p. 2841-2849.
34. Zhao, S. and L. Li, Chemical Isotope Labeling LC-MS for Metabolomics. Adv Exp Med Biol, 2021. 1280: p. 1-18.
35. Marsh, A.N., et al., Skyline Batch: An Intuitive User Interface for Batch Processing with Skyline. J Proteome Res, 2022. 21(1): p. 289-294.
36. Morton, J., V.A. Carolan, and P.H.E. Gardiner, Removal of exogenously bound elements from human hair by various washing procedures and determination by inductively coupled plasma mass spectrometry. Analytica Chimica Acta, 2002. 455(1): p. 23-34.
37. Chang, Y.-J., et al., A high-throughput method based on microwave-assisted extraction and liquid chromatography–tandem mass spectrometry for simultaneous analysis of amphetamines, ketamine, opiates, and their metabolites in hair. Analytical and Bioanalytical Chemistry, 2014. 406(9): p. 2445-2455.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94741-
dc.description.abstract隨著全世界與非法藥物相關的事故與犯罪增加,法醫毒理學家監測藥物使用模式變得至關重要。在傳統的檢測方法中,尿液與血液的檢測區間較短,很難清楚地瞭解使用歷史。因此,頭髮的毒物分析已經成為調查使用時間序的一種流行方法。然而,相較於前兩者生物檢體,頭髮樣本中殘留的藥物含量較低,且不易檢測。因此,在本研究中,我們目的在於開發一種超靈敏的方法,利用化學衍生化來增加偵測靈敏度,同時利用化學同位素標記法(CIL)來將頭髮樣本中的安非他命類興奮劑(ATS)及其他含胺類非法藥物做定量分析。
在本篇研究中,我們利用真實的法醫檢體去針對頭髮的前處理步驟,如去污、分段以及粉碎化進行充分地評估。此外,我們也優化了頭髮萃取的方法。而針對化學衍生化效率,也在反應時間與反應溫度中進行最佳化實驗。樣本的分析使用了LC-MS/MS以及MRM模式。最終方法在準確度、精確度、線性、檢測最低檢測極限以及定量極限方面進行方法確效。我們將該方法與無化學衍生標記的方法進行比較,以評估化學衍生法的增強效益。該方法成功應用在法醫頭髮樣本以及商業的藥物頭髮檢體中。我們預期此結果可以有助於法醫毒物學在藥物使用的調查。
zh_TW
dc.description.abstractIllicit drug related accidents and crimes are surging worldwide and it is important for forensic toxicologist to monitor the drug usage patterns. Conventionally, detection windows of illicit drugs in urine and blood are short and hard to have clear picture of consuming history. Thus, hair analysis has become one of popular method to investigate the chronological drug usages. However, the drug remained in hair samples compared to biofluids is relatively low and not easy to detect. Therefore, in this study, we aim to develop an ultrasensitive method to monitor amphetamine-type stimulants (ATS) and other amine-containing drugs by applying dansylation and chemical isotope labeling approach (CIL) to increase detection sensitivity and quantification in hair specimens.
The hair preparation procedures including decontamination, segmentation and pulverization were fully evaluated by examining authentic forensic hair. In addition, we optimize extraction method for hair sample. The labeling efficiency was carefully evaluated by examining reaction time and reaction temperature. LC-MS/MS with MRM mode will employe for analysis. The finalized method was further validated in terms of accuracy, precisions, linearity, LOD and LOQ. The validated method was compared with label-free methods to evaluate the enhancement factors by CIL approach. The method was successfully applied to the forensic hair specimens and commercial multidrug hair specimens. We anticipate that this work could benefit forensic toxicological investigation on drug usages.
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dc.description.tableofcontentsContent

致謝 1
中文摘要 3
Abstract 4
Abbreviation list: 5
Ch.1 Introduction 10
1.1 Amphetamine-type drug and other amine-containing drugs 10
1.2 Forensic drug test in hair 12
1.3 Derivatization and Chemical isotope labeling (CIL) 15
1.4 Aim of this study 16
Ch.2 Method and material 17
2.1 Chemical and reagent 17
2.2 Sample preparation 17
2.2.1 Decontamination 17
2.2.2 Segmentation and pulverization 17
2.2.3 Hair extraction methods 18
2.3 Dansyl chloride derivatization 18
2.4 Liquid chromatography and tandem mass spectrometry 19
2.5 Method validation 19
2.5.1 Linearity 19
2.5.2 LOD and LOQ 20
2.5.3 Precision and accuracy 20
2.6 Data analysis 20
Ch.3 Results and discussion 21
3.1 Preparation of hair specimen 21
3.1.1 Optimization of decontamination 21
3.1.2 Optimization of segmentation and pulverization methods 22
3.1.3 Optimization of extraction methods 22
3.2 Chemical isotope labeling-ATS 23
3.2.1 Analytical work flow for ATS-drugs 23
3.2.2 Optimization of derivatization methods 23
3.2.3 Evaluation of derivatization 24
3.2.4 Synthesis of Chemical isotopic labeling (CIL) approach 25
3.3 Method validation 25
3.4 Method application 26
Ch.4 Conclusion 27
Ch.5 Figures 28
Figure 1. Residues of contaminated hair after wash. 28
Figure 2. Effect of scissor sizes on the hair homogenization. 29
Figure 3. Effect of pulverization in hair preparation. 31
Figure 4. Effect of reaction conditions on hair extraction. 32
Figure 5. Proposed workflow for DnsCl-based CIL on determining amine-containing drugs. 33
Figure 6. The chemical structures of dansylated amphetamine, amphetamine- type stimulants and amine-containing drugs. 34
Figure 7. Effect of reaction temperature and time on derivatization efficiency. 36
Figure 8. MRM chromatograms. 37
Figure 9. Chromatograms of light labeled and heavy labeled proton of eight representative amphetamine-type stimulants. 38
Figure 10. Sensitivity evaluation of representative dansylated amphetamine-type stimulants and amine-containing drugs. 39
Figure 11. Results of method application. 43
Ch.6 Tables 44
Table 1. All authentic standards with vender and catalog number. 44
Table 2. MRM transitions and retention time of dansyled 26 anaylytes. 47
Table 3. LODs of 26 amphetamine-type stimulants (ATS) and amine-containing drugs. 53
Table 4. Calibration curves, coefficient of determination, precision and accuracy of 26 amphetamine-type stimulants (ATS) and amine-containing drugs. 55
Reference 60
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dc.language.isozh_TW-
dc.subject苯丙胺類物質zh_TW
dc.subject化學同位素標記zh_TW
dc.subject非法藥物zh_TW
dc.subject頭髮zh_TW
dc.subjecthairen
dc.subjectchemical isotope labeling (CIL)en
dc.subjectAmphetamine-type substances (ATS)en
dc.subjectLC-MSen
dc.title在頭髮中使用化學同位素標記分析苯丙胺類物質和含氨基之非法藥物zh_TW
dc.titleAnalyzing Amphetamine-type substances (ATS) and amine-containing illicit drug with chemical isotope labeling (CIL) in hairen
dc.typeThesis-
dc.date.schoolyear112-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee廖曉偉;翁德怡zh_TW
dc.contributor.oralexamcommitteeHsiao-Wei Liao;Te-I Wengen
dc.subject.keyword頭髮,化學同位素標記,苯丙胺類物質,非法藥物,zh_TW
dc.subject.keywordhair,chemical isotope labeling (CIL),Amphetamine-type substances (ATS),LC-MS,en
dc.relation.page64-
dc.identifier.doi10.6342/NTU202401096-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2024-06-25-
dc.contributor.author-college醫學院-
dc.contributor.author-dept法醫學研究所-
dc.date.embargo-lift2029-06-05-
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