簡易檢索 / 詳目顯示

回結果列表
研究生： 林立川
Li-Chan Lin
論文名稱： 氣相層析質譜法對亞甲雙氧甲基安非他命類毒品之旋光性與2,5-二甲氧基-4-乙硫基苯乙胺(2C-T-2)之分析研究
指導教授： 林震煌
Lin, Cheng-Huang
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2003
畢業學年度： 91
語文別： 中文
中文關鍵詞： 2,5-二甲氧基-4-乙硫基苯乙胺 、亞甲雙氧甲基安非他命 、氣相層析質譜法
英文關鍵詞： 2C-T-2, MDMA, GC/MS
論文種類： 學術論文
相關次數： 點閱：317  下載：0 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 中文摘要
    3,4-methylenedioxyamphetamine（3,4-MDA）、3,4-methylenedioxy-
    methamphetamine（3,4-MDMA）會因為立體中心的而會有不同的神經毒性。故本研究以S-(－)-N-(trifluoroacetyl)prolyl chloride（S-TPC）試劑衍生上具立體中心的3,4-MDA、3,4-MDMA，並利用氣相層析質譜儀來證明成功分離3,4-MDA、3,4-MDMA的R、S form，另外將衍生物層析分離、水解得到單一立體中心的產物。
    本研究對新興苯乙胺類濫用藥物2-(4-ethylsulfanyl)-2,5-dimeth-
    oxyphenylethylamine （2C-T-2）所做的定性分析與代謝成分分析。在定性分析中訂出70eV的EI質譜（m/z：241，212，197，183，153）。代謝成分分析上是將20mg/kg的量注射大白鼠，蒐集24hr的尿液進行分析研究。所蒐集的尿液在經過加酸加熱水解和乙醚的萃取濃縮之後，利用氣相層析質譜儀加上模擬類似藥物2C-B的代謝途徑找到2-(4-ethylsulfanyl-2,5-dimethoxy-phenyl)-ethanol、1-acetoamino-2-
    (2-hydroxy-4-ethylsulfanyl-5-methoxyphenyl)-ethane以及1-aceto-
    amino-2-(2-methoxy-4-ethylsulfanyl-5-hydroxyphenyl)-ethane的代謝物，並且以選擇離子（SIM）的方式確認之。

    Abstract
    For 3,4-methylenedioxyamphetamine (3,4-MDA)、3,4-methylenedi-
    oxymethamphetamine (3,4-MDMA), different stereoisomers cause different neurotoxicity. In this study, we describe a simple method for R- and S-isomer by reaction of S-(－)-N-(trifluoroacetyl)prolyl chloride (S-TPC). Using gas chromatography / mass spectrometry separated derivatives of 3,4-MDA and 3,4-MDMA successfully. Furthermore, we could separate and hydrolyze the derivatives, then we could gain the single form of 3,4-MDA and 3,4-MDMA.
    A simple and specific method based on gas-chromatography-selected
    ion monitoring mass spectrometry (GC-SIM-MS) for the analysis of in vivo metabolism of 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) in rats is described. Three male rats were administered 20 mg/kg of 2C-T-2 by intra-peritoneal injection, and 24h urine fractions were collected before and after administration for analysis. After hydrolysis of the urine samples, the metabolites were extracted by liquid-liquid extraction and analyzed by a quadruple mass spectrometer in the selected ion monitoring mode. The findings show that three metabolites of 2-(4-ethylsulfanyl-2,5-dimethoxyphenyl)-ethanol (MW: 242), 1-acetoamino-2-(2-hydroxy-4-ethylsulfanyl-5-methoxyphenyl)-ethane (MW: 269) and 1-acetoamino-2-(2-methoxy-4-ethylsulfanyl-5-
    hydroxyphenyl)-ethane (MW: 269) are present and the metabolic pathway for 2C-T-2 in the rat is proposed.

    目錄 中文摘要….………………………………………………………….i 英文摘要…………………………………………………………… ii 目錄..………………………………………………………………..iii 圖目錄………………………………………………………………vi 表目錄………………………………………………………………ix 第一章、緒論……………………………………………………………1 1-1 分析物簡介………………………………………………………….1 1-1-1 MDMA系列毒品…………………………………………….1 1-1-2 2C-T-2………………………………………………………...5 1-2 研究目的…………………………………………………………….9 1-2-1 MDA與MDMA的鏡相異構物分離……………………….9 1-2-2新興毒品2C-T-2的性質與代謝……..…………………….11 第二章、各類濫用藥物特性以及質譜分析……………………………13 2-1 濫用藥物種類……………………………………………………...13 2-1-1中樞神經抑制劑…………………………………………….13 2-1-2中樞神經興奮劑…………………………………………….15 2-1-3 幻覺劑……………………………………………………...16 2-2濫用藥物的檢測方法以及質譜儀的分析…………………...16 2-2-1揮發性的興奮劑與麻醉止痛劑的鑑定法………………….17 2-2-2非揮發性的興奮劑與麻醉止痛劑的鑑定法………………18 第三章、儀器、藥品與實驗方法………………………………………20 3-1 儀器………………………………………………………………...20 3-1-1 氣相層析質譜法…………………………………………...20 3-1-2 氣相層析儀………………………………………………...21 3-1-3 界面…………………………….…………………………..26 3-1-4 質譜儀……………………………………………………...27 3-1-5 資料處理…………………………………………………...31 3-1-7 質譜儀校正…………………………………….…………..32 3-1-8 氣相層析質譜儀個裝置之廠牌、型號、規格……………34 3-1-9 其他儀器、器材之廠牌、型號、規格……………………35 3-2 藥品………………………………………………………………...36 3-3 MDA與MDMA鏡相異構物之分離……………………………...38 3-3-1 S-TPC之合成……………………………………………….38 3-3-2 S-TPC與MDA、MDMA的衍生反應…………………….39 3-3-3 管柱層析以及水解條件…………………………………...40 3-3-4 GC-MS的最佳化…………………………………………...41 3-3-5 氣相層析條件……….……………………………………..41 3-4 2C-T-2的性質以及代謝物的分析…………………………………42 3-4-1 2C-T-2的氣相層析條件…………………..……………….42 3-4-2 老鼠的代謝實驗…………………………………………...42 3-4-3 尿液的水解與萃取………………………………………...43 3-4-4 2C-T-2代謝物的氣相層析條件……………………………47 第四章、結果討論……………………………………………………...48 4-1 MDA、MDMA鏡相異構物的分離………………………………48 4-1-1 利用GC-MS分離衍生物情形以及質譜解析……………..48 4-1-2 衍生物經管柱層析後以GC-MS確認分離情形…………..52 4-1-3 單一立體中心產物與毛細管電泳結合…………………….55 4-2 對新興濫用藥物2C-T-2性質與代謝物成分分析……………….57 4-2-1 2C-T-2藥品的氣相層析質譜圖……………………………..57 4-2-2 2C-T-2代謝物路徑推測……………………………………..60 4-2-3 老鼠尿液中2C-T-2殘餘藥量測試…………………………63 4-2-4 老鼠尿液中代謝物鑑定…………………………………….65 4-2-5 老鼠尿液中代謝物的質譜解析…………………………….70 4-2-6 酸性條件與鹼性條件萃取比較…………………………….74 4-2-7 其他老鼠實驗……………………………………………….76 第五章、結論…………………………………………………………..80 參考資料………………………………………………………………..81 發表論文………………………………………………………………..88

    參考資料
    1. Ensslin, H.K.; Kovar, K-A.; Maurer, H.H., Toxicological detection of the designer drug 3,4-methylenedioxyethylamphetamine (MDE, “Eve”) and its metabolites in urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay. J. Chromatogr. B 683 (1996) 189
    2. Maurer H.H.; Bickeboeller-Friedrich, J.; Kraemer, T.; Peters, F.T., oxicokinetics and analytical toxicology of amphetamine-derived designer drugs (‘Ecstasy’). Toxicol. Letters 112-113 (2000) 133
    3. Sadeghipour, F.; Veuthey, J. -L., Sensitive and selective determination of methylenedioxylated amphetamines by high-performance liquid chromatography with fluorimetric detection J. Chromatogr. A 787 (1997) 137
    4. 管制藥品管理局/公告區/認清MDMA的真面目：Http://210.241.68.101/circular/circular_16-1.asp
    5. 管制藥品管理局/預警宣導組/使用快樂丸保證讓你呆：Http://210.241.68.101/circular/circu.ar_10.asp
    6. Robert Mathias. Ecstasy damages brain and impairs memory in human. NIDA Dotes, 1999, 14(4): 10－11.
    7. Zicker P. Annual survey finds increasing teen use of Ecstasy, Steroids. NIDA Notes, 2001, 16(2): 6－7.
    8. 曹家琪、連智、劉志民，MDMA濫用：歷史和現況，中國藥物依賴性雜誌，2001年 第10卷 第3期
    9. Brady, J.F., Di Stephano, E.W., and Cho, A.K., Spectral and inhibitory interactions of (+/-) 3,4-methylenedioxyamphetamine (MDA) and (+/-) 3,4-methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes. Life Sci. 39 1457-1464
    10. Ricaurte, G.A., Bryan, G., Strauss, L. Seiden, L. and Schuster, C. Hallucinogenic amphetamine selective destroys brain serotonin nerve terminals, Science 1985 (229) 986-988
    11. Naranjo, C., Shulgin A.T. Sargent, T., Evaluation of 3,4-methylene-
    dioxyamphetamine(MDA) as an adjunct to psychotherapy. Med Pharmacol. Exper, 1967 (17) 359-364
    12. Turek , I.S., Soskin , R.A., Kurland, A.A., Methylenedioxyamphet
    -amine(MDA) subjective effects, J. Psychedelic Drugs. 1974 6(1) 7-13
    13. UTRILLA, P., Pharmacological Aspect of Amphetamines Ars Pharmaceutica, 2000 67-77
    14. Izyaslav Lapin, Phenibut (β-phenyl-GABA):A Tranquilizer and Nootropic Drug, CNS Drug review 2001 (7) 471-481
    15. http://pub.iams.sinica.edu.tw/lab/wbtzeng/Chem_fun/love_chemical.html
    16. http://www.cjdaily.com.cn/big5/content/2003-04/25/content_265832.htm
    17. Alexander and Ann Shulgin, Phenethylamines I Have Known And Loved:A Chemical Love Story
    18. 柳如宗，防範新型毒品犯罪-----安非他命類毒品之濫用趨勢與對策，憲兵學術半年刊第55期
    19. Snyder SH., and Richelson E., Steric models of drugs predcting psychedelic activity. In: Psychotomimetic drugs Raven, NY, 1970, pp43
    20. Marsh DF., and Herring DA., The pharmacological activity of the ring methyl substituted phenisopropylamines. J. Pharmacol. Exp. Ther., 1950 (100) 298-308
    21. Harris SC., and Worley RC., Analgesic properties of xylopropamine. Proc. Soc. Exp. Bio. Med., 1957, (95) 212-215
    22. King A., and van-der Meer AP., New synyhetic drugs in the European Union, Science & justice, 2001 (41) 200-202
    23. Karla A.M., Ashraf M., Marcella F. F., Alphonse P., Distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methlenedioxy
    amphetamine stereoisomers in fatal poisoning, Forensic Science Inter-
    national 1996 (83) 111-119
    24. Stone D.M., Stahl D.C., Hanson G.R. and Gibb G.W., The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methlene-
    dioxyamphetamine (MDA) on monoaminergic systems in the rat brain, Eru. J. Pharmacol., 1986 (128) 41-48
    25. Schmidt C.J., Neurotoxicity of the psychedelic amphetamine, methyl-
    enedioxymethamphetamine . J. Pharmacol Exp. Ther., 1987 (240) 1-7
    26. Hensley D., Cody, J.T.,
    27. Donna H., John T. C., Simultaneous determination of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA), methylene-
    Dioxymethamphetamine (MDMA), and methylenedioxyethylamphet-
    Amine (MDEA) enantiomers by GC-MS, J. Anal. Toxicol. 1999 (23) 518-523
    28. Lim H.K., Su Z., Foltz R.L., Stereoselective disposition: enantioselec-
    tive quantitation of 3,4-methylenedioxymethamphetamine and three of its metabolites by gas chromatography electron capture negative ion chemical ionization mass spectrometry, Biolog. Mass Spect., 1993 (22) 403-411
    29. Robert L.F., Robert V.B., John A. R., Richard A. G., Seterochemistry of the metabolism of MDMA to MDA, Life Sciences, 1989 (45)295-301
    30. Fitzgerald R.L., Blanke R.V., Glennon R.A., Tousif M.Y., Determina-
    tion of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymeth
    amhetamine enantiomers in whole blood, J of Chromatog. 1989 (490) 59-69
    31. Zhou F.X., Krull I.S., Chromatographia, 1993 (35) 153-159
    32. Desai D.M., Gal J., J. Chromatogr., 1993 (629) 215-228
    33. Rizzi, A.M., Hirz R., Cladrowa-Rurge, S., Josson, H., Chromatogra
    -phia 1994 (39) 131-137
    34. Matsushima, k., Nagai T., Kamiyama S., J. Anal. Toxicol., 1998 (22) 33-39
    35. Emmanuel V., Jena-Luc V., Chiral separation of amphetamines by high-performance capillary electrophoresis, J. Chromatog. A, 1995 (717) 219-228
    36. Iwata Y.T., Garcia A., Kanamori T., Inoue. H., Kishi T., Lurie I.S., The use of a highly sulfated cyclodextrin for the simultaneous chiral separation of amphetamine-type stimulants by capillary electrophoresis, Electrophoresis, 2002 (23) 1328-1334
    37. Fanali S., Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors, J. Chromatog. A, 2000 (875) 89-122
    38. Hung Y.U., Liu J.T., Lin L.C., Lin C. H., Chiral seperation of 3,4-methylenedioxymethamphetamine and related compounds in clandestine tablets and urine samples by capillary electrophoresis
    /fluorescence spectroscopy, Eletrophoresis, 2003 (24) 1097-1104
    39. Munehiro K., Hitoshi T., Update on clandestine amphetamines and their analogues recently seen in Japan, J. Heal. Sci. 2002 (48) 14-21
    40. Sally F., John F., Arylethylamine psychotropic recreational drugs:a chemical perspective, Eur. J. Med. Chem. 2002 (37) 527-539
    41. Tatsuyuki K., Hiroyuki I., Tuko Iwata., Yoshihito O, Tohru K., In vivo metabolism of 4-bromo-2.5-dimethoxyphenethylamine (2C-B) in rat:identificatin of urinary metabolites, J. Anal. Toxicol. 2002 (26) 61-66
    42. Tatsuyuki K., Kenji T., Yoshihito O., Hiroyuki I., Yoshio I., Tohru K., Excretory profile of 4-bromo-2.5-dimethoxyphenethylamine (2C-B) in rat, J. Heal. Sci., 2003 (49) 166-169
    43. 林杰樑，臨床毒品藥物濫用學
    44. Bailcy D.N., Manogverra A.S., Survey of drug-abused patterns and toxicology analysis in an emergency room population, J. Anal. Toxico. 1980 (4) 199-203
    45. Kellerman A.L., Fihn S.D., Logerfro J.P., Utilization and yield of drug screening in the emergency room, AM. J. Emerg. Med, 1988 (6) 14-20
    46. Byatt C, Volans G: Sedative and hypnotic drugs, Br. Med. J., 1984 (289) 1214-1217
    47. Mccarron M., Schulze B., Walberg C., Short acting barbiturate over dorage. Correlation of intoxication score with serum barbiturate concentration, JAMA. 1982 (248) 55-61
    48. Caradoc-Davies T.H., Opiate toxicity in elderly patients, Br. Med. J., 1981 (283) 905-906
    49. Martin W.R., Pharmacology of opioid. Pharmacol Rev, 1984 (35) 285-323
    50. Gary N.E., Saidi P., Methamphetamine intoxication, a speedy new treatment. Am. J. Med., 1978 (64) 537-540
    51. Gal J., Amphetamine in nasal in halers, T. Toxicol. Clin. Toxicol., 1982 (19) 577-578
    52. Barish P., Tintinalli J., Designer drugs and amphetamines, Philadelphia, 1990 770-780
    53. Smith J.A., Walter G., Johnston D., LSD “flash back” as a cause of diagnosis error, Postgrad Med., 1982 (140) 518-520
    54. Mercieca J. Brown E.A., Acute renal failure due to rhabdomyolysis associated with use of a strait jacket in LSD intoxication, Br. Med. J. 1984 (288) 1949-1950
    55. 行政院國家科學委員會精密儀器發展中心，質譜分析專論。
    56. Lho D.S., Donike M., Shin H.S., Kang B.K., Park J.S., Systematic analysis of stimulants and narcotic analgesics by gc chromatography with nitrogen specific detection and mass spectrometry, J. Anal. Toxicol. 1990 (14)) 73-76
    57. Baselt R.C., Disposition of toxic drugs and chemicals in man, Biomedical Pulbication, 1982
    58. Lho D.S., Donike M., Hong J.K., Park H.K., Lee J.A., Park J.S., Determination of phenolalkylamines: narcotic analgesics and beta-blockers by gas chromatography/mass spectroscopy, J. Anal. Toxicol. 1990 (14) 77-83
    59. Skoog, Holler, Nieman, Instrument Analysis, 5th, p. 703
    60. Skoog, Holler, Nieman, Instrument Analysis, 5th, p.704
    61. Karasek F.W., Clemant R.E., Basic gas chromatography-mass spectrometry, Elseire science publishing company Inc., 1988
    62. Skoog, Holler, Nieman, Instrument Analysis, 5th,
    63. Skoog, West, Holler, Analytical Chemistry, 7th, p. 695
    64. Message G.M., Quardrupole Storage Mass spectrometry, New York, Wiley, 1989
    65. Silverstein R.M., Bassler G.C., Morrill T.C., Spectrometric identification of organic compounds, 5th ed., p. 4
    66. Message G.M., Partical aspects of chromatography/mass spectro-
    metry, chapter 5, 1984
    67. Watson J.T., Introduction to mass spectrometry, p. 247

    無法下載圖示
    QR CODE