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研究生: 廖安淑
An-Shu Liau
論文名稱: 發展簡易的β-環糊精修飾毛細管電泳法對毒品與吸毒者尿液中甲基安非他命類光學異構物的分離與分析
The chiral separation of methamphetamine and related compounds in clandestine tablets and urine samples by beta-cyclodextrine modified capillary electrophoresis
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: 2004
畢業學年度: 93
語文別: 中文
論文頁數: 109
中文關鍵詞: β-環糊精毛細管電泳法甲基安非他命光學異構物
英文關鍵詞: beta-cyclodextrine, capillary electrophoresis, methamphetamine, chiral separation
論文種類: 學術論文
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  • 本研究的主要重點在於發展以毛細管電泳法,結合β-CD對鏡像異構物的選擇能力,成功的將 (±)-甲基安非他命、(±)-麻黃酮、(±)-麻黃素、(±)-假麻黃素分離開來,並可用於鑑定這些鏡像異構物在毒品粉末和吸毒者尿液中的分布。在研究過程中,比較了β-CD濃度大小、溫度高低、電壓大小和有機修飾劑在緩衝溶液中的比例等變因對電泳結果的影響,以找出最佳的電泳條件。本研究成果,發現以CE/UV法來分離偵測這些鏡像異構物,不但快速簡便,而且解析度高,可彌補GC/MS在分析鏡像異構物時必須事先作複雜的衍生工作才能達成目的之不足,所以此方法對於法庭檢驗和臨床分析上有很大的幫助。
    本研究找到最佳分離上述分析物的緩衝溶液為:磷酸鹽濃度150 mM、β-CD濃度17.5 mM、溶劑比例H2O/ACN = 95/5;最佳的電泳條件為:溫度範圍在15 ~ 30 C之間,電壓範圍在20 ~ 25 kV之間。如此就能不需要做任何的樣品前處理工作,即能在20分鐘的時間之內完成分析檢驗工作,偵測極限約可達1 ppm (S/N = 3/1)。

    The chiral separation of (±)-methamphetamine, (±)-methcathinone, (±)-ephedrine and (±)-pseudoephedrine by means of beta-cyclodextrine modified capillary electrophoresis is described. The distribution of enantiomers in clandestine tablets and urine samples were identified. Several electrophoretic parameters, such as the concentration of -cyclodextrin, temperature, the applied voltage and the amount of organic solvent required for successful separation were optimized. The method, as described herein, represents a good complementary method to GC/MS for use in forensic and clinical analysis.
    The optimum CE conditions for the analysis of these analytes was achieved using a mixture of water-acetonitril solution (95:5, v/v) containing phosphate (150 mM), -CD (17.5 mM) at 15 ~30 C; applied voltage: 20 ~ 25 kV. This method proposed here can provide results in less than 20 min without any complicated pre-treatments and provided a ~1 ppm detected limit for methamphetamine related compounds.

    中文摘要………………………………………………………………………I 英文摘要……………………………………………………………………II 目錄…………………………………………………………………………III 圖目錄…………………………………………………………………………V 表目錄………………………………………………………………………VI 第一章、緒論…………………………………………………………………1 1-1. 分析物簡介………………………………………………………1 1-1-1. 甲基安非他命…………………………………………………2 1-1-1.1 甲基安非他命性質簡介………………………………………2 1-1-1.2 甲基安非他命的合成…………………………………………4 1-1-2. 麻黃素、假麻黃素…………………………………………………5 1-2. 研究目的…………………………………………………………7 第二章、分析方法與原理………………………………………………….10 2-1. 毛細管電泳層析法之介紹………………………………………10 2-1-1. 毛細管電泳層析方法的發展……………………………………10 2-1-2. 毛細管電泳層析方法的基本原理………………………………13 2-1-2.1 電泳的分離:電泳遷移率與電滲流……………………………13 2-1-2.1.1 電泳遷移率……………………………………………………14 2-1-2.1.2 電滲流 (EOF)…………………………………………………16 2-1-2.2 分散過程…………………………………………………………20 2-1-2.3 分離度……………………………………………………………22 2-2. 對掌性選擇劑分離對掌異構物之機制…………………………24 2-2-1. 對掌異構物分離的發展…………………………………………24 2-2-2. 應用環糊精分離對掌異構物之機制……………………………27 第三章、儀器與藥品………………………………………………………30 3-1. 毛細管電泳儀……………………………………………………30 3-2. 儀器及周邊設備列表……………………………………………31 3-3. 藥品列表…………………………………………………………32 3-4. 緩衝溶液的配製…………………………………………………34 3-5. 毛細管的前處理與後處理………………………………………35 第四章、實驗過程與討論 4-1. 標準品的分離與分析……………………………………………37 4-1-1. 緩衝溶液未加β- CD時的分離結果……………………………37 4-1-2. 添加β- CD於緩衝溶液中的分離結果…………………………39 4-1-3. 標準品完全分離的結果…………………………………………41 4-1-4. 將(±)-amphetamine添加於標準品中…………………………43 4-2. 電泳條件的選擇…………………………………………………44 4-2-1. 電壓大小對分離效果的影響……………………………………44 4-2-2. 溫度高低對分離效果的影響……………………………………46 4-2-3. 不同β- CD濃度對分離效果的影響……………………………48 4-2-4. 不同有機修飾劑比例對分離效果的影響………………………50 4-3. 吸毒者尿液的萃取與分析………………………………………52 4-3-1. 尿液樣品的保存與前處理………………………………………52 4-3-2. 尿液樣品的萃取…………………………………………………52 4-3-3. 尿液樣品的分析…………………………………………………54 4-4. 毒品粉末之萃取與成份分析……………………………………58 4-4-1. 毒品粉末成份的萃取……………………………………………58 4-4-2. 毒品粉末成份的分析……………………………………………59 4-5. 甲基安非他命毒品粉末之鏡像分布分析………………………63 第五章、結論與展望………………………………………………………66 發表論文……………………………………………………………………68 參考文獻……………………………………………………………………69 附錄一、尿液樣品的檢驗電泳圖譜………………………………………73 附錄二、毒品粉末的電泳圖譜……………………………………………85 附錄三、甲基安非他命毒品粉末的鏡像鑑定電泳圖譜…………………91 附錄四、四組鏡像標準品線上濃縮(stacking)之電泳圖譜……………107 附錄五、標準品的UV吸收光譜……………………………………………109

    1. 行政院/衛生署/管制藥品管理局/常見濫用藥物分類圖鑑http://www.nbcd.gov.tw/prop/poison/all_03.htm
    2. J. L. Cadet, S.V. Ordonez, J. V. Ordonez, Synapse. 25 (1997) 176-184.
    3. X. Deng, B. Ladenheim, L. I. Tsao, and J. L. Cadet, Journal of Neuroscience. 19(22) (1999) 10107-10115.
    4. U. D. McCann, D. F. Wong, F. Yokoi, V. Villemagne, R. F. Dannals, G. A. Ricaurte, Journal of Neuroscience. 18(20) (1998) 8417- 8422.
    5. F.T. Noggle, J. DeRuiter, C.R. Clark, Anal. Chem. 58 (1986) 1643-1648.
    6. S. Smith, J. Chem. Soc. 1927, 2056.
    7. F. T. Noggle, J. DeRuiter, C. R. Clark, J. Forensic Sci. 31 (1986) 732-742.
    8. H. F. Skinner, Forensic Sci. Int. 48 (1990) 123-134.
    9. F. T. Noggle, J. DeRuiter, C. R. Clark, J. Chromatogr. Sci. 28 (1990) 529-536.
    10. M. J. LeBelle, C. Savard, B. A. Dawson, D. B. Black, L.K. Katyal, F. Zrcek, A.W. By, Forensic Sci. Int. 71 (1995) 215-223.
    11. J. Pfordt, Z. Fresenius, Anal. Chem. 325 (1986) 625-626.
    12. F. T. Noggle, J. Deruiter, C.R. Clark, J. Chromatogr. Sci. 28 (1990) 529-536.
    13. S. Palfrey, M. Labib, Ann. Clin, Biochem. 33 (1996) 344-346.
    14. C. L. Flurer, L. A. Lin, R. D. Satzger, K. A. Wolnik, J. Chromatogr. B. 669 (1995) 133-139.
    15. D. Scarcella, F. Tagliaro, S. Turrina, G. Manetto, Y. Nakahara, F. P. Smith, M. Marigo, Forensic Sci. Int. 89 (1997) 33-46.
    16. W. Maruszak, M. Trojanowicz, M. Margasińska, H. Engelhardt, J. Chromatogr. A. 926 (2001) 327-336.
    17. I. Bokor, V. C. Trenerry, P. Scheelings, Forensic Sci. Int. 85 (1997) 177-192.
    18. A. Ramseier, C. Siethoff, J. Caslavska, T. Wolfgang, Electrophoresis. 21 (2000) 380
    19. M. Lanz, R. Brenneisen, W. Thormann, Electrophoresis. 18 (1997) 1035
    20. D.E.Cox, K.R.Wiliams, Forensic Sci. Int. 77 (1996) 101
    21. F. Kohlrausch, Wiedemanns Ann., Phys. Chem. 62(1897) 209-239.
    22. S. Hjerten, Chromatogr. Rev. 9 (1967) 122
    23. R. Virtanen, Acta Polytechnica Scand. 123 (1979) 1
    24. J. W. Joegenson, K. D. Lukacs, J. Chromatogr. 218 (1981) 209
    25. J. W. Joegenson, K. D. Lukacs, Anal. Chem. 53 (1981) 1298
    26. S. K. Otsuka, K. Ichikawa, A. Tsuchiya, T. Ando, Anal. Chem. 56 (1984) 111
    27. K. H. Row, W. H. Griest, M. P. Maskarienc, J. Chromatogr. 409 (1987) 193
    28. S. Hjerten, M. D. Zhu, J. Chromatogr. 346 (1985) 265
    29. A. Cohen, B. L. Karger, J. Chromatogr. 397 (1987) 409
    30. X. Huang, R. N. Zare, Anal. Chem. 63 (1991) 2193
    31. X. Huang, M. J. Gorden, R. N. Zare, Anal. Chem. 60 (1988) 375
    32. R. T. Kennedy, J. W. Jorgenson, Anal. Chem. 61 (1989) 1128
    33. C. Y. Yan, R. Dadoo, R. N. Zare, D. J. Rakestraw, D. S. Anex, Anal. Chem. 68 (1996) 2767
    34. N. David, Heiger High Performace Capillary Electrophoresis-An Intorduction, 1992, 2nd edition.
    35. A. M. Krstulovic, Chiral Separations by HPLC, Ellis Horwood Ltd., Chichester, 1989.
    36. E. J. Ariens, Clin. Pharmacol. Ther. 42 (1987) 361.
    37. E. J. Ariens, E. W. Wuis, E. F. Veringa, Biochem. Pharmacol. 37 (1988) 9.
    38. D. W. Armstrong, G. L. III Reid, M. L. Hilton, C. –D. Chang, Environ. Pollution. 79 (1993) 51.
    39. 〝FDA′s Policy Statement for the Development of New Stereuisomeric Drugs,〞Fed. Reg. 57 (1992) 22249
    40. E. L. Eliel, Stereochemie der Kohlenstoffverbindungen, Verlag Chemie, Weinheim, 1966.
    41. Blaschke, G. Angew, Chem. Int. Ed. Engl. 19 (1980) 13.
    42. D. W. Armstrong, G. L. III Reid, M. L. Hilton, C. –D. Chang, W. Y. Li, J. Agri. Food Chem. 38 (1990) 1674.
    43. K. H. Ekborg-Ott, D. W. Armstrong, Chiral Separations, S. Ahuja, Ed., American Chemical Society, Washington, D. C., 1997, pp. 201.
    44. G. Eglinton, Calvin, M. Sci. Am. 216 (1967) 32.
    45. Philip, R. P. Chem. Eng. News 64 (1986) 28.
    46. D. W. Armstrong, Y. Tang, Zukowski, J. Anal. Chem. 63 (1991) 2858.
    47. D. W. Armstrong, E. Y. Zhou, J. Zukowski, Kosmowska-Ceranowicz, B. Chirality 8(1996) 39.
    48. P. M. Helfman, ; Bada, J. L. Proc, Nat. Acad. Sci, U.S.A. 72 (1975) 2891.
    49. P. M. Masters, J. L. Bada, J. S. Zigler, Jr Nature. 268 (1977) 71.
    50. J. L. Bada, Chemistry and Biochemistry of Amino Acid, G. C. Barrett, Ed., Chapman and Hall. New York, 1985, p. 6.
    51. K. Robbie, M. J. Brett, A. Lakhtakia, Nature 384 (1996) 616.
    52. Hinze, W. L. Sep. Purif. Methods 10 (1981) 159
    53. E. Varesio and J. L. Veuthey, J. Chromatogr. A. 717 (1995) 219-228.
    54. M. R. Baylor and D. J. Crouch, Am. Assoc. Clin. Chem. 14 (1993) 103-110.
    55. K. A. Moore, A. Mozayani, M. F. Fierro and A. Poklis, Forensic Sci. Int. 83 (1996) 111-118.
    56. J. Szejtli, Cylodextrin in drug formulations: part I, Pharm. Technol. Int., 3 (1991) 15-23.
    57. http://www.beckmancoulter.com/
    58. C-R. Sabine, H. Robert and K. Ernst, R. Andreas. J. Chromatogr. A. 710 (1995) 339-345.
    59. T. Schmitt and H. Engelhardt, J. Chromatogr. A. 697 (1995) 561-570.
    60. T. Nagai, K. Matsushima, T. Nagai, Y. Yanagisawa, A. Fujita, A. Kurosu and S. Tokudome, J. Anal. Toxicol. 24 (2000) 140-145.

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