臺灣博碩士論文加值系統

藥物濫用已成為全球性的健康與社會問題。除了對使用者個人健康造成傷害、增加醫療與社會成本之外，也可能因其精神恍惚或失智而傷害他人。國內的情況也日益嚴重，除了常見的安非他命、海洛因外，新興毒品包括K他命、搖頭丸、大麻等毒品的濫用也有逐漸增加的趨勢。近年來，有許多的研究不斷在開發新的生物檢體來監測濫用藥物的情形；在本研究中，利用氣相層析質譜儀(GC/MS)檢測唾液、尿液及毛髪中常見的濫用藥物及其代謝物：如安非他命類藥物(安非他命、甲基安非他命、 MDMA、MDA)、鴉片類藥物(嗎啡、可待因、海洛因)之探討比較不同的藥物在此三種不同檢體中的代謝時間及濃度相關性。在本實驗中，將藥物由真實檢體經萃取取出，再衍生後直接以氣相層析質譜儀分析。在真實檢體部分，由監所協助採集6位新入監服刑收容人的尿液、唾液及毛髪檢體分別以GC/MS進行測定，探討藥物經過人體代謝系統後，在三種不同生物檢體所檢測之藥物濃度相關性。實驗結果證實尿液可檢測到較高之藥物濃度，且尿液、毛髪之藥物濃度含有較一致相關性，而毛髪追溯期為三種檢體最長，約理髪後第二次後便測不到，且無殘留性，在未來可提供司法系統對檢測濫用藥物更有效的方向。

The drugs of abuse have been a healthy and social problem over the world. Beside to damage the user’s individual health, increase the medical service and the social cost, the drugs also can cause the user spirit absent and loses the wisdom to injure other people. The situation of domestic is also serious day by day. Besides amphatamine and heroin, the use of ketamine, opiates and methylenedioxymethamphe tamine (MDMA) also have increased gradually.
In past research, the gas chromatograph mass spectrometer(GC/MS) has been used to confirm the drugs of abuse. In this study, we analyze the concentration correlation between the saliva, urine and hair for multiple drugs of abuse, such as amphetamines (amphetamine; AP, methamphetamine; MA, methylenedioxy- amphetamine; MDA, MDMA, methylenedioxy- ethylamphetamine; MDEA), ketamine (ketamine; K, norketamine; NK), opiates (morphine; MOR, codeine; COD and 6-mono acetylmorphine; 6-AM) using gas chromatograpgy/mass spectrometry(GC/MS). We compare the different metabolism time of this three samples. We use different methods to extract the drugs in these three samples. After deriving, the extraction was analyzed in using GC/MS.
We collect the urine, saliva and hair samples of six new prisons to analyze the correlation between two among these three samples for multiple drugs of abuse by using GC/MS. The results indicate that we can detect the drugs effect of amphetamine in the urine about three to five days. The drugs effect of morphine in the urine samples can be detected about one to two days. In our research, we use the Heptafluoro butyric acid anhydride (HFBA) to be the derivation to detect the drug correlation in saliva. The drugs effect just can stay in the saliva about one day. When the drugs were weaved into the hair, we can detect the drugs effect after one month. So we can know that there are different metabolic rates for different drugs and the concentration correlation between urine and hair samples.

中文摘要 Ⅰ
英文摘要 II
目錄 IV
圖目錄 VI
表目錄 VIII
中英文及縮寫對照 X
第一章 前言 1
1-1 藥物濫用之簡介與概況 1
1-2 台灣藥物濫用史 2
1-3 濫用藥物介紹 6
1-4 尿液檢驗 18
1-5 唾液檢驗 20
1-6 毛髪檢驗 25
1-7 氣相層析質譜儀 32
1-8 研究動機 38
第二章 材料與方法 40
2-1 藥品與試劑 40
2-2 標準品與內標準品儲存溶液製備 41
2-3 實驗儀器設備 43
2-4 實驗方法 45
2-5 氣相層析質譜分析條件 51
2-6 氣相層析質譜偵測方法確效性評估 55
2-7 檢體採集計劃 57
第三章 常見濫用藥物GC/MS之檢測方法建立 58
3-1尿液檢驗確效性評估 58
3-2唾液檢驗確效性評估 64
3-3毛髪檢驗確效性評估 71
3-4真實樣品分析 76
第四章 結論與未來展望 89
參考文獻 91

1.行政院衛生署管制藥品管制局98年3月藥物濫用案件暨檢驗統計資料
2.United Nations ODCCP. Global Illicit Drug Trends.New York.2001
3.J. Shafer. Designer drugs. Science. 80:60-70(1990)
4.行政院衛生署管制藥品管制局常見濫用藥物分類圖鑑
5.孫嘉蘭, 高雄醫學大學職業安全衛生研究所碩士論文, 2001.
6.李志恒, 藥物濫用,行政院衛生署管制藥品管理局, 2002.
7.陳晉昇, 國立東華大學化學研究所碩士論文, 2001
8.Wagner B.K., O''Hara D.A. Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients. Clin Pharmacokinet. 33, 426-453,1997.
9.Leong H.S., Tan N.L., Lui C.P., Lee T.K. Evaluation of Ketamine Abuse Using Hair Analysis: Concentration Trends in a Singapore Population. J Anal Toxicol. 29, 314-318, 2005.
10.Moeller M.R. Hair Analysis as Evidence in Forensic Cases. Ther Drug Monit. 18, 444-449, 1996.
11.Morrison J.F., Chesler S.N., Yoo W.J., Selavka C.M. Matrix and Modifier Effects in the Supercritical Fluid Extraction of Cocaine and Benzoylecgonine from Human Hair. Anal Chem. 70, 163-172, 1998.
12.Ryan J. Huxtable and Stephan K. W. Schwarz. The Isolation of Morphine-First Principles in Science and Ethics. Molecular Interventions. 1, 189-191, 2001.
13.Cone E.J., Welch P, Mitchell J.M., Paul B.D. Forensic drug testing for opiates: I. Detection of 6-acetylmorphine in urine as an indicator of recent heroin exposure; drug and assay considerations and detection times. J Anal Toxicol. 15, 1-7, 1991
14.D, R.;M, C.M.; Lambert, W. E.; Huestis, M. A. Urine drug testing for opioids, cocaine, metabolites by direct injection liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass. Spectrom. 17,(14),1665-1670, 2003
15.行政院衛生署97年7月藥物食品安全週報第146期
16.Mandel I.D., The diagnostic uses of saliva, J. Oral Pathol. Med. 19, 119-125, 1990.
17.Haeckel R, Hanecke P. The application of saliva, sweat and tear fluid for diagnostic purposes. Ann. Biol. Clin. (Paris). 51, 903-910, 1993
18.Oosterhuis H.J, G.H., Bohn Stafleu Van Loghum, Klinische neurologie, Houten, 1999.
19.Moore P.A., Guggenheimer J, Etzel K.R., Weynant R.J., Orchard T. Type 1 diabetes mellitus, xerostomia and salivary flow rates. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol. 92, 281-291, 2001.
20.Bohn Stafleu Van Loghum, Amerongen van Nieuw, Systemische aandoeningen en speeksel, in: A. van Nieuw Amerongen (Ed.), Speeksel, speekselklieren en mondgezondheid. Houten. 241-257, 2004.
21.Lin A.L., Johnson D.A., Patterson T.F., Wu Y, Lu D.L., Shi Q, Yeh C.K. Salivary anticandidal activity and saliva composition in an HIV-infected cohort. Oral Microbiol. Immunol. 16, 270–278, 2001.
22.Epstein S.R., Mandel I.D., Scopp I.W. Salivary content in hemodialysis patients. J. Periodontol. 51, 336-338, 1980.
23.Maseda C, Hama K, Fukui Y, Matsubara K, Takahashi S, Akane A. Detection of delta-9 THC in saliva by capillary GC/ECD after marihuana smoking. Forensic Sci Int. 32, 259-266, 1986.
24.Thompson L.K., Cone E.J. Determination of delta 9-tetrahydrocannabinol in human blood and saliva by high-performance liquid chromatography with amperometric detection. J Chromatogr. 421, 91-97, 1987.
25.Drummer O.H. Drug testing in oral fluid. Clin Biochem Rev. 27, 147-159, 2006.
26.Samyn N, Laloup M, Boeck G.D. Review: Bioanalytical procedures for determination of drugs of abuse in oral fluid. Anal Bioanal Chem. 388,2007.
27.Choo R.E., Huestis M.A. Oral fluid as a diagnostic tool. Clin Chem Lab Med. 42, 1273-1287, 2004.
28.Aps J.K., Martens L.C. Review: The physiology of saliva and transfer of drugs into saliva. Forensic Sci Int. 150, 119-131, 2005.
29.Kintz P, Samyn N. Use of alternative specimens: drugs of abuse in saliva and doping agents in hair. Therap. Drug Monit. 24, 239-246, 2002.
30.Kadehjian L. Legal issues in oral fluid testing. Forensic Sci Int. 150, 151-160, 2005.
31.Walsh J.M., de Gier J.J., Christopherson A.S., Verstraete A.G. Drugs and driving. Traffi c Inj Prev. 5, 241-253, 2004.
32.Cingolani M, Scavella S, Mencarelli R, Mirtella D, Froldi R, Rodriguez. D. J Anal Toxicol. 28, 128, 128-131, 2004.
33.Lin DL, Yin RM, Liu HC, Wang CY, Liu RH. J Anal Toxicol. 28, 411-417, 2004.
34.Wada M., Nakashima K. Anal Bioanal Chem. 385, 413-415, 2006.
35.Kintz P, Villain M, Cirimele V. Ther Drug Monit. 28, 442-446, 2006.
36.Baumgartner AM, Jones PF, Baumgartner WA, Black CT. J. Nucl. Med. 20, 748-752, 1979.
37.Klug E. Z. Rechtsmed. 84, 189, 1980.
38.Suzuki O, Hattori H. Koenshu-Iyo Masu Kenkyukai. 8, 201, 1983
39.Marigo M, Tagliaro F, Poiesi C, Lafisca S, Neri C. J. Anal. Toxicol. 10, 158, 1986.
40.Boumba VA, Ziavrou KS, Vougiouklakis T. Int J Toxicol. 25,143-163, 2006.
41.Pragst F, Balikova MA. Clin Chim Acta. 370, 17-49, 2006.
42..Kintz, P. Drug Testing in Hair. 1996.
43.http://hongkongskin.com/2007/12/17/hair-removal
44.Paxton J.W. Measurement of drugs in saliva: a review, Methods Find. Exp. Clin. Pharmacol. 1, 11–21, 1979.