臺灣博碩士論文加值系統

探討、評估及蒐集安非他命類藥物以不同試劑進行衍生化反應後以氣相層析質譜分析。在化學衍生技術方面使用矽烷化、乙醯化、烷化等類衍生劑，在這些衍生化反應中，選擇適合之衍生化試劑，評估其滯留時間、定量離子、定性離子、離子交互貢獻、離子豐度、解析度、波峰形狀影響。在化學衍生技術方面使用十二種衍生試劑。部分衍生試劑需在水溶液中才能與安非他命類藥物進行衍生化反應，其他試劑可直接添加至標準品內，以加熱方式進行衍生化反應。
研究發現同位素稀釋內標安非他命-d5（ring）衍生產物之斷裂碎片大都與安非他命-d0相同，故其離子交互貢獻無法計算，同位素稀釋內標安非他命-d5（ring）不適合作為定量用之內標準品。最終選擇PFPA為最理想之衍生劑，並選用交互貢獻度最小之同位素稀釋內標安非他命-d11、甲基安非他命-d14，並建立一套最適化方法；記錄各種衍生方法之標準圖譜，建立完整之分析法。
進行單衍生和雙衍生實驗，單衍生化學反應使用PFPA，雙衍生化學反應則使用PFPA與MTBSTFA，利用兩種不同的衍生方法來比較安非他命與甲基安非他命經過不同衍生反應後，其衍生物產物在氣相層析/質譜儀上的分析效能的差異及圖譜特異性。
本研究在安非他命之單衍生反應與雙衍生反應檢量線範圍皆為40-5000 ng/mL，線性相關係數(r2)皆在0.999以上，偵測極限與定量極限為40 ng/mL、40 ng/mL，回收率為85~90%之間；甲基安非他命之衍生反應檢量線範圍為40-5000 ng/mL，線性相關係數(r2)皆於0.995以上；偵測極限與定量極限為40 ng/mL、40 ng/mL；回收率為82~76%。
安非他命與甲基安非他命因化學結構不同，氮上氫能被衍生劑取代的數目相異，故利用此特性使用單衍生與雙衍生反應進行比較，在相同的分析條件下，
雙衍生反應較單衍生反應有較佳的分離效果，安非他命衍生物及甲基安非他命衍生物的總離子層析圖在雙衍生反應更加對稱、且較少拖尾。本研究並以23個甲基安非他命陽性尿液檢體經過稀釋、液相-液相萃取、化學衍生等前樣品前處理步驟，最後以氣相層析質譜儀進行分析，以探討單化學衍生與雙化學衍生反應對真實樣品分析之差異。

1. 物質濫用，行政院衛生署指導，行政院衛生署管制藥品管理局製作，2003
2. 徐健民，刑事化學，中央警察大學出版社，2003
3. 濫用藥物尿液檢驗機構認可基準，中華民國九十年八月二十一日行政院衛生
署 衛署管藥字第０九０００五五五四０號公告
4. 施多喜，甲基安非他命安非他命麻黃素等系列覺醒劑之鑑析，刑事科學31，
民國八十年三月
5. P. S. Stout, K. L. Klette, C. K. Horn, “Evaluation of ephedrine, pserdoephedrine and phenylpropanolamine concentrations in human urine samples and a comparison of the specificity of DRI amphetamines and abuscreen online (KIMS) amphetamines screening immunoassays”, J. Forensic Sci., 2004, 49(1), 160-164
6. E. Howard Taylor, P. Pat, “Evaluation of the drugcheck 9 on-site immunoassay test cup according to a standard method validation protocol”, J. Anal. Toxicol., 2004, 28, 190-197
7. K. M. Jenkins, M. S. Young, C. R. Mallet, “Mixed-mode solid-phase extraction procedures for the determination of MDMA and metabolites in urine using LC-MS, LC-UV, or GC-NPD”, J. Anal. Toxicol., 2004, 28, 50-58
8. S. M. Wang, Y. S. Giang, Y. C. Ling, “Simultaneous supercritical fluid extraction and chemical derivatization for the gas hromatographic- isotope dilution mass spectrometric determination of amphetamines in urine”, J. Chromato. B, 2001, 759, 17-26
9. 王勝盟、蔡麗琴、江雲生、凌永健，超臨界流體萃取結合化學衍生技術應用於尿液中非他命之鑑析，警政學報28，民國八十五年，頁91-104
10. 王勝盟、陳瑞廣、蔡麗琴、姜雲生、凌永健，以驅取法配合氣相層析/同位素稀釋質譜法檢測尿液中之安非他命，刑事科學41，民國八十五年三月
11. Jordi Segura, Rosa Ventura, Carmen Jurado,“Review Derivatization procedures for gas chromatographic–mass spectrometric determination of xenobiotics in biological samples,with special attention to drugs of abuse and doping agents”, J. Chromato. B., 1998, 713, 61–90
12. 周念陵副執行長，實驗室評鑑標準ISO 17025之介紹 ，財團法人全國認證基金會
13. 王勝盟，簡化前處理技術配合質譜術分析安非他命類藥物之研究，國立清華大學博士論文
14. Furnari C, Ottaviano V, Rosati F, Tondi V:“Identification of 3,4-methylenedioxy-
Amphetamine analogs encountered in clandestine tablets“, Forensic Sci Int 1998;92:49-58.
15. J. M. Fujimoto, R. I. H. Wang, “A method of identifying nacrotic analogesics in human urine after therapeutic doses”, Toxicol. Appl. Pharm., 1970, 16, 186.
16. R. H. Liu, B. A. Goldberger,中譯本編輯-徐建民，工作場所藥物檢驗彙編
17. 楊聰財、馮煥光、林玉財，安非他命濫用、成癮、中毒及其治療，國防醫學，81 年12 月15 日，p541-544
18. 李朝雄、林信男，安非他命(1)：縱說，當代醫學第十八卷、第二期，80年2月，P11~13
19. Hand book of Analytical derivatization Reaction,Daniel R. Knapp
20. 林志哲，煙毒犯吸食安非他命類藥物後之代謝物剖繪：不同採尿時點及頭髮區段之追蹤分析，中央警察大學碩士論文
21. 吳慶鴻，自動化固相萃取法結合化學衍生技術應用於安非他命類藥物之鑑析，中央警察大學碩士論文
22. 陳江和，安非他命及甲基安非他命光學異構物之氣相層析質譜鑑析，中央警察大學碩士論文
23. 黎添來，氣相層析質譜法應用於生物檢體中鴉片類藥物之鑑析，中央警察大學碩士論文
24. 柳如宗、姚清發，簡易萃取衍生法應用於尿液中甲基安非他命與安非他命之氣相層析質譜分析，刑事科學45，民國八十七年三月
25. C.L Hornbeck, R.J. Czarny,“Quantitation of methamphetamine and amphetamine in urine by Capillary GC/MS. Part I. Advantages of trichloroacetyl derivatization”, J. Anal. Toxicol. 13 (1989) 144–149.
26. C.L. Hornbeck, J.E. Carrig, R.J. Czarny,“Detection of a GC/MS artifact peak as methamphetamine”, J. Anal. Toxicol. 17 (1993) 257–263.
27. J.B. Jones, L.D. Mell Jr.,“A simple wash procedure for improving chromatography of HFAA derivatized amphetamine extracts for GC/ MS analysis”, J. Anal. Toxicol. 17 (1993) 447.
28. R.B. Gilbert, P.I. Peng, D. Wong,“A labetalol metabolite with analytical characteristics resembling amphetamines”, J. Anal. Toxicol. 19 (1995) 84– 86.
29. B.K. Gan, D. Baugh, R.H. Liu, A.S. Walia,“Simultaneous analysis of amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples by solid-phase extraction, derivatization, and gas chromatography/mass spectrometry”, J. Forensic Sci. 36 (1991) 1331–1341.
30. R. Melgar, R.C. Kelly,“A novel GC/MS derivatization method for amphetamines”, J. Anal. Toxicol. 17 (1993) 399–402.
31. J.T. Cody, R. Schwarzhoff,“Interpretation of methamphetamine and amphetamine enantiomer data”, J. Anal. Toxicol. ,1993:(17) ,321–326.
32. 簡易萃取衍生法應用於尿液中甲基安非他命與安非他命之氣相層析質譜分析，柳如宗、姚清發，刑事科學，第四十五期，八十七年三月
33. Manami Nishida*，Akira Namera，Mikio Yashiki，Kojiro Kimura,“Miniaturized sample preparation method for determination of amphetamines in urine”, Forensic Sci Int; 2004:(143)163-167
34. Manami Nishida*, Akira Namera, Mikio Yashiki, Tohru Kojima,“Routine analysis of amphetamine and methamphetamine in biological materials by gas chromatography–mass spectrometry and on-column derivatization”, J. Chromato. B,2003:(789) , 65–71
35. Manami Nishida*, Akira Namera, Mikio Yashiki, Tohru Kojima,“On-column derivatization for determination of amphetamine and methamphetamine in human blood by gas chromatography–mass spectrometry”，Forensic Sci Int; 2002:(125)156–162
36. Hege Grefslie Ugland, Mette Krogh *, Knut E. Rasmussen,“Automated determination of ‘Ecstasy’ and amphetamines in urine by SPME and capillary gas chromatography after propylchloroformate derivatisation”,Journal of Pharmaceutical and Biomedical Analysis,1999:(19) 463–475
37. Stacy D. Brown*，Daniel J. Rhodes，Boyd J. Pritchard ,“A validated SPME-GC-MS method for simultaneous quantification of club drugs in human urine”, Forensic Sci Int;2006
38. J. Rohrich*，G. Kauert,“Determination of amphetamine and methylenedioxy-amphetamine-derivatives in hair”
39. Sheila J. Asghar*，Glen B. Baker，Gail A. Rauw，Peter H. Silverstone,“A rapid method of determining amphetamine in plasma samples using pentafluorobenzenesulfonyl chloride and electron-capture gas chromatography”, Journal of Pharmacological and Toxicological Methods ,2002:(46)111-115
40. Hallvard Gjerde*，Inger Hasvold，Grete Pettersen，and Asbjorg S. Christophersen ,“Determination of Amphetamine and Methamphetamine in Blood by Derivatization with Perfluorooctanoyl Chloride and Chromatography/Mass Spectrometry”, J. Anal. Toxicol.,Vol. 17 ,March/April 1993
41. Amitava Dasgupta*，Omar Yousef,“Gas chromatographic-mass spectrometric determination of serum mexiletine concentration after derivatization with perfluorooctanoyl chloride,a new derivative”，J. Chromato. B, 1998:(705)283-288
42. Kazuo Okajimaa,b, Akira Nameraa*, Mikio Yashikia, Ichiro Tsukueb, Tohru Kojimaa, “Highly sensitive analysis of methamphetamine and amphetamine in human whole blood using headspace solid-phase microextraction and gas chromatography/mass spectrometry”, Forensic Sci Int; 2001 : (116) 15-22
43. Motoyasu Sato *, Toshiyuki Mitsui,“Rapid and simple determination of methamphetamine and amphetamine in blood by simultaneous extraction- derivatization”, Journal of Pharmaceutical and Biomedical Analysis,1997 :(16) 139-145
44. Namera A.; Yashiki M.; Kojima T.; Ueki M.,“Automated Headspace Solid-Phase Microextraction and In-Matrix Derivatization for the Determination of Amphetamine-Related Drugs in Human Urine by Gas Chromatography–Mass Spectrometry”, J. Chromato. Sci., 2002,:(7)19-25
45. Lisha Mao, Chengjun Sun∗, Hong Zhang, Yongxin Li, Desheng Wu,“Determination of environmental estrogens in human urine by high performance liquid chromatography after fluorescent derivatization with p-nitrobenzoyl chloride”, Analytica Chimica Acta, 2004 :(522) 241–246
46. Hongyan Li a'*, Qizhi Hu b, Xuequen Yang a, Zhiren Zhou a ,“Direct determination of 4-nitrobenzoyl chloride by highperformance liquid chromatography based on silanophilic interaction”, J. Chromato. A, 1995:(710) 347-350
47. Yasushi Horia,b ,*, Manami Fujisawaa,b, Kenji Shimadaa, Mitsuru Satoc, Michio Kikuchic,c b Masao Hondac , Yasuo Hiroseb,“Quantitative determination of glufosinate in biological samples by liquid chromatography with ultraviolet detection after p-nitrobenzoyl derivatization”
48. R. H. Liu,“Elements and Practice in Forensic Drug Urinalysis”,Central Polce University Press,Taiwan,ROC,1994.
49. J. RGhrich, G. Kauert,“Determination of amphetamine and methylenedioxy
-amphetamine-derivatives in hair”, Forensic Sci Int.,1997:(84)179-188
50. Valentine JL etc: GC-MS Determination of Amphetamine and Methamphetamine in Human Urine for 12 Hours Following Oral Administration of Dextro-Methamphetamine: Lack of Evidence Supporting the Established Forensic Guidline for Methamphetamine Confirmation.,J Anal Toxicol 1995:(19)581-590.