(3.238.96.184) 您好!臺灣時間:2021/05/12 16:08
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:張元哲
研究生(外文):Yuan-Jhe
論文名稱:以大體積注射於氣相層析質譜儀-負離子化學游離法提升大麻毛髮檢驗之靈敏度
論文名稱(外文):Sensitivity Enhancement of Cannabinoids Hair Testing using Large-Volume Injection and Gas chromatography-Mass Spectrometry with Negative Ion Chemical ionization
指導教授:張耀仁張耀仁引用關係
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:醫學分子毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:85
相關次數:
  • 被引用被引用:0
  • 點閱點閱:282
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
毛髮有別於其他的生物檢體,能提供長時間性的藥物使用歷程紀錄,可將血液中所含之小分子化合物,如同錄音帶忠實地將藥物紀錄在毛髮內部,其採集不具侵入性、方便,具有寬廣的檢驗時窗 (半年以上)。因此近 20 年來,毛髮檢驗獲得了高度的重視,尤其是在法庭科學中濫用藥物的檢驗上,濫用藥物施用在毛髮檢驗上幾乎已達到無所遁形的地步。大麻為目前全世界濫用藥物中最為廣泛的一項,然而大麻主要代謝物大麻酸於毛髮中濃度極低,於是毛髮中大麻的檢驗仍是極大的分析挑戰,根據美國 SAMHSA (Substance Abuse and Mental Health Services Administration) 所訂定之檢測閾值為 0.05 pg/mg,因此大麻毛髮檢驗必須具備有極高之靈敏度,一般皆需使用到極昂貴之氣相層析串聯式質譜儀-化學負離子游離法。本研究嘗試以大體積注射,搭配單一四極柱質譜儀氣相層析譜,增加檢體進樣量,與改進前處理回收率及提升高質量傳送效率來提升大麻毛髮檢驗之靈敏度。目前結果顯示:由於固相萃取方法之改進,回收率已由原有之 23 % 提升至93 %,且經由 SPE 與 HPLC 純化使背景干擾有效降低。最後,透過大體積注射與調整參數獲得高質量傳送效率提升,偵測極限可達 0.05 pg/mg。

The detection of cannabinoids in hair is a great analytical challenge. Due to the weak incorporation rate of the acidic metabolite into the hair matrix, the concentration of 11-nor-Δ9-Tetrahydrocannabinol-9- carboxylic acid (THC-COOH) is very low. The relatively low concentration of cannabinoids in hair can be explained by the following: THC is highly bound to protein in plasma, THC exhibits no melanin affinity, and a negatively charged compound like 9-carboxy-THC will be repelled by the hair matrix. Therefore, SAMHSA suggested 1 pg/mg as the initial cutoff concentration for marijuana metabolites and 0.05 pg/mg as the cutoff concentration for the confirmatory test. The determination THC-COOH in human hair required very high sensitivity. In general, the conventional technique to detect the low concentration of THC-COOH is GC/MS-MS instrumentation. However, GC/MS-MS has few disadvantages like to expensive and difficult to operate. In this study, a high sensitive and specific GC/MS-NCI method, based on large-volume programmed-temperature vaporization (LV-PTV) injection, has been developed for the analysis assay of THC-COOH in hair. Hair specimens were washed, alkaloid hydrolysis, then subjected to solid-phase extraction to reduce matrix, and a 25 μL aliquot of an extract was injected using large-volume injection technique, finally analyzed with negative chemical ionization mass spectrometry (GC/MS-NCI). According this result, the recovery of THC-COOH in this method could reach 93 %. Our method utilizes large-volume injection could obviously improved sensitivity and the detection limit was 0.05 pg/mg. This is the publication describing the use of large-volume injection and NCI mass spectrometry for the determination of THC-COOH in hair.

中文摘要...................................................I

英文摘要..................................................II

總目錄...................................................III

圖目錄.....................................................V

表目錄...................................................VII

第一章 緒論.............................................1
1-1 大麻簡介及藥理毒害...............................1
1-2 大麻之代謝機制...................................5
1-3 大麻於不同生物檢體之檢測.........................7
1-4 毛髮檢驗.........................................9
1-5 毛髮之生理與結構................................10
1-6 藥物進入毛髮之機制..............................12
1-7 大麻毛髮檢驗分析回顧............................15
1-8 氣相層析質譜儀..................................19
1-9 大體積注射原理..................................24
1-10 研究動機........................................26
第二章 材料與方法......................................28
2-1 藥品與試劑......................................28
2-2 工作溶液之配製..................................29
2-3 儀器設備........................................31
2-4 分析條件........................................35
2-5 化學衍生流程....................................37
2-6 實驗方法........................................38
2-7 分析方法確效評估................................46
第三章 毛髮中大麻酸之分析方法建立......................50
3-1 大麻酸衍生化及質譜分析建立......................50
3-2 毛髮中大麻酸之萃取方法評估......................56
3-3 儀器靈敏度評估..................................60
3-4 大體積注射評估..................................62
3-5 高質量傳送效率之提升............................65
3-6 液相層析分離純化之評估..........................71
3-7 方法之確效性評估................................73
3-8 毛髮真實檢體評估................................78
第四章 結論與未來展望..................................79
參考文獻 ................................................81


[1]M Uhla, H Sachs. Cannabinoids in hair: strategy to prove marijuana/ hashish consumption. Forensic Science International. 2004, 145,143–147.
[2]P Kintz. Analytical and Practical Aspects of Drug Testing in Hair. Forensic Science Series. 2006,127-141.
[3]林士欽, 高雄醫學大學藥學研究所碩士論文, 2001年.
[4]C Staub. Chromatographic procedures for determination of cannabinoids in biological samples, with special attention to blood and alternative matrices like hair, saliva, sweat and meconium. Journal of Chromatography B. 1999, 733, 119–126.
[5]F Musshoff, B Madea. Review of Biologic Matrices (Urine, Blood, Hair) as Indicators of Recent or Ongoing Cannabis Use. Therapeutic Drug Monitoring. 2006,28, 155–163.
[6]M.R. Moeller, S Steinmeyer, T Kraemer. Determination of drugs of abuse in blood. Journal of Chromatography B. 1998, 713, 91–109.
[7]H Sachs, P Kintz. Testing for drugs in hair Critical review of chromatographic procedures since 1992. Journal of Chromatography B. 1998, 713, 147–161.
[8]D.A. Kidwell, J.C. Holland, S Athanaselis. Testing for drugs of abuse in saliva and sweat. Journal of Chromatography B. 1998, 713, 111–135.
[9]C Moore, A Negrusz, D Lewis. Determination of drugs of abuse in meconium. Journal of Chromatography B. 1998, 713. 137–146.
[10]A Reiter, J Hake, C Meissner. Time of drug elimination in chronic drug abusers. Case study of 52 patients in a “low-step” detoxification ward. Forensic Science International. 2001, 119, 248–253.
[11]A.S. Kielland, B Skuterud, J Morland. Urinary excretion of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and cannabinoids in frequent and infrequent drug users. Journal of Analytical Toxicology. 1999, 23, 323–332.
[12]R Marsili1, S Martello, M Felli, S Fiorina, M Chiarotti. Hair testing for Δ9-THC-COOH by gas chromatography/tandem mass spectrometry in negative chemical ionization mode. Rapid Commun. Mass Spectrom. 2005, 19, 1566–1568.
[13]R.W. Goldblum, L.R. Goldbaum, W.N. Piper. Barbiturate concentrations in the skin and hair of guinea pigs. Journal of Investigative Dermatology. 1954, 22, 121–128.
[14]V Cirimele, P Kintz, P Mangin. Tseting human hair for cannabis.Forensic Science International. 1995, 70, 175-182.
[15]M.R. Moeller. Hair Analysis as Evidence in Forensic Cases. Therapeutic Drug Monitoring. 1996, 18, 444-449.
[16]L Skender, V Karacic, I Brcic, A Bagaric. Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography/mass spectrometry. Forensic Science International. 2002, 125, 120-126.
[17]Y Nakahara, R Kikura, K Takahashi. Hair analysis for drugs of abuse VIII : Effective extraction and determination of 6-acetylmorphine and morphine in hair with trifluoroacetic acid-methanol for the confirmation of retrospective heroin use by gas chromatography-mass spectrometry. J Chromatography B Biomedical Application. 1994, 657, 93-101.
[18]G.L. Henderson. Mechanisms of drug incorporation into hair. Forensic Science lnternational. 1993, 63, 19-29.
[19]M.A. Huestis, R.A. Gustafson, E.T. Moolchan, A Barnes, J.A. Bourland, S.A. Sweeney, E.F. Hayes, P.M. Carpenter, M.L. Smith. Cannabinoid concentrations in hair from documented cannabis users. Forensic Science International. 2007, 169, 129–136.
[20]V Spiehler. Hair analysis by immunological methods from the beginning to 2000. Forensic Science International. 2000, 107, 249.
[21]T Mieczkowski. A research note: the outcome of GC/MS/MS confirm of hair assays of 93 cannabinoid (+) cases. Forensic Science International. 1995, 70, 83.
[22]C Moore, F Guzaldo. The Determination of 11-nor-Δ9-Tetrahydrocannabinol- 9-Carboxylic Acid (THC-COOH) in Hair using Negative Ion Gas Chromatography–Mass Spectrometry and High-Volume Injection. Journal of Analytical Toxicology. 2001, 25, 555-558.
[23]T Mieczkowski. Assessing the potential of a ”color effect” for hair analysis of 11-nor-9-carboxy-Δ9-Tetrahydrocannabinol analysis of a large sample of hair specimens. Life Sciences. 2003, 74, 463.
[24]F Musshoff. Full automated determination of cannbinoids in hair samples using headspace solid-phase microextraction and gas chromatography-mass spectrometry. Journal of Analytical Toxicology. 2002, 26, 554.
[25]P.V. Monasanto. Hair analysis for Δ9-THC, Δ9-THC-COOH, CBN and CBD by GC/MS-EI: comparison with GC/MS-NCI for Δ9-THC-COOH. Forensic Science International. 2002, 128, 66.
[26]H Sachs, U Dressler. Detection of THCCOOH in hair by MSD-NCI after HPLC clean-up, Forensic Science International. 2000, 107, 239–247.
[27]C Moore, S Rana, C Coulter, F Feyerherm, H Prest. Application of Two-Dimensional Gas Chromatography with Electron Capture Chemical Ionization Mass Spectrometry to the Detection of 11-nor-Δ9-Tetrahydrocannabinol-9-carboxylic Acid (THC-COOH) in Hair. Journal of Analytical Toxicology.2006. 30, 4.
[28]R.H. Liu, D.E. Gadzala. Handbook of Drug Analysis. 1997.
[29]J Teske, K Putzbach , W Engewald , R.K. Mu¨ller. Determination of cannabinoids by gas chromatography–mass spectrometry and large-volume programmed-temperature vaporizer injection using 25 mL of biological fluid. Journal of Chromatography B. 2002, 772, 299–306.
[30]D Clay, R Anderson. Thermo Electron Corporation, Milan, Italy. Large Volume Injections with a Programmed Temperature Vaporizing Injector for Gas Chromatography. Thermo electron corporation application note 10036.
[31]E Hoh, K Mastovska. Large volume injection techniques in capillary gas chromatography. Journal of Chromatography A. 2008, 1186, 2–15.
[32]K Blau, J.M. Halket. Handbook of Derivatives for Chromatography-Second Edition. John Wiley & Sons Limited. 1977.
[33]Derivatization Reactions for GAS Chromatography/Mass Spectrometry. American Academy of Forensic Sciences. 1995.
[34]吳雅雪,中山醫學大學醫學分子毒理研究所博士論文,2008年.
[35]S Huq, A Dixon, K Kelly, M.R. Krishna Kallury. Novel solid-phase extraction protocol for 11-nor-9-carboxy-9-tetrahydro cannabinol from urine samples employing a polymeric mixed-mode cation-exchange resin, Strata-X-C, suitable for gas chromato graphy–mass spectrometry or liquid chromatography–mass spectrometry analysis. Journal of Chromatography A. 2005, 1073, 355–361.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
系統版面圖檔 系統版面圖檔