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研究生:魏志嶽
研究生(外文):Chih-Yueh Wei
論文名稱:以層析質譜技術進行新興濫用藥物系統性分析方法之研究
論文名稱(外文):Systematic toxicological analysis of emerging drugs of abuse using chromatography-mass spectrometry
指導教授:王勝盟王勝盟引用關係
指導教授(外文):Sheng-Meng Wang
學位類別:碩士
校院名稱:中央警察大學
系所名稱:鑑識科學研究所
學門:軍警國防安全學門
學類:警政學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:151
中文關鍵詞:新興濫用藥物氣相層析質譜液相層析串聯式質譜液相萃取
外文關鍵詞:designer drugsGC/MSLC/MS/MSliquid-liquid extraction
相關次數:
  • 被引用被引用:4
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  • 下載下載:121
  • 收藏至我的研究室書目清單書目收藏:0
本研究以氣相層析電子撞擊式質譜儀(GC/MS)和液相層析電灑式離子阱質譜儀(LC/MS/MS)進行新興濫用藥物的鑑定分析,並建立質譜資料庫以供國內實務檢驗上的參考。
在GC/MS方面,新興安非他命類藥物DOB、DOM、DMA、PMA、MMDA及苯乙胺類藥物2C-B、2C-C、2C-T2、2C-T7、2C-I共10種藥物及其氘取代同位素標準品,分別以TFA、PFPA、HFBA、Acetyl、l-TPC五種試劑衍生進行分析方法的確效。多數衍生藥物在40-1000 ng/mL的檢量線範圍內具有良好線性關係(r2>0.99),定量極限可達40到100 ng/mL,日內、間變異多小於10%,回收率大於80%。
在LC/MS/MS方面,除了新興安非他命類和苯乙胺類藥物外,另再針對色胺類和哌嗪類等不易以GC/MS衍生分析的藥物進行系統性分析,目前已建立43個新興濫用藥物的液相層析圖和一次、二次質譜資訊,進而擴充實驗室自建的資料庫以供搜尋比對之用。其中針對34個藥物進行分析方法確效的評估,其檢量線範圍在10-1000 ng/mL之間多具有良好的線性關係(r2>0.995),定量極限除少數藥物外也多可達20 ng/mL,日內、間變異多小於10%,回收率多數大於70%,基質效應在71.85%到123.54%之間。
在真實尿液樣品方面,本研究以LC/MS/MS資料庫比對分析,後續再進行GC/MS和LC/MS/MS定量分析,安非他命類與愷他命類藥物定量結果多與認證實驗室所提供的數值相當,而本研究使用的非酸水解萃取方式測得的是尿液中自由態嗎啡和自由態可待因,因此低於總嗎啡和總可待因含量,另外在某些鴉片類藥物使用者尿液樣品中同時偵測到6-乙醯嗎啡的存在,可確認為海洛因之施用。
In this study, we developed a method for identification of new emerging drugs by GC/MS and LC/MS/MS. Liquid-liquid extraction method was applied. The GC/MS method was validated for the qualification and quantification of the emerging amphetamines (DOB, DOM, DMA, PMA, MMDA) and the phenethylamine series (2C-B, 2C-C, 2C-T-2, 2C-T-7, 2C-I) derivatized with TFA, PFPA, HFBA, acetyl and l-TPC. The linear ranges were 40-1,000 ng/mL with good linearity (r2>0.99). The limit of qutification was between 40 and 100 ng/mL for most analytes. The intra- and inter-day precisions were within 10% and the mostly recoveries were above 80%.
Systematic analysis using LC/MS/MS was also performed to identify 43 designer drugs, including piperazine derivatives, tryptamine derivatives and previously mentioned anphetamines. The LC/MS/MS database containing extracted ion chromatogram and mass spectrum has been constructed and incorporated with the existing MS/MS libaray. The LC/MS/MS method was validated in the linearity range of 10-1,000 ng/mL (r2>0.995). The limit of qutification could be as low as 20 ng/mL for most analytes. The intra- and inter-day precisions were within 10% and the mostly recoveries were above 70%. Matrix effects were in the range from 71.85% to 123.54%.
The established methods were then applied to the analysis of real samples obtained from certified laboratory. The qutification results showed consistency between GC/MS and LC/MS/MS. The concentration of free morphine and free codeine we analysed without acid hydrolysis is lower than one of total morphine and total codeine. 6-Acetylmorphine can also be detected from the urines of opium abusers and thus confirmed heroin use.
中文摘要 I
Abstract III
目錄 IV
圖次 VI
表次 IX
第一章 緒論 1
1.1研究動機與目的 1
1.2分析方法之探討 3
第二章 研究方法 7
2.1樣品前處理 7
2.1.1液相-液相萃取法 7
2.1.2固相萃取法 8
2.2化學衍生原理 8
2.3層析質譜儀器原理 10
2.4氣相層析質譜分析 11
2.5液相層析質譜分析 13
2.6基質效應之評估 14
第三章 實驗材料與方法 16
3.1藥品與試劑 16
3.2儀器設備 22
3.3氣相層析質譜分析方法 22
3.4液相層析質譜分析方法 24
3.5萃取方法 25
3.5.1液相-液相萃取法 25
3.5.2 TOXI-tubes A(商業液相-液相萃取套組) 26
3.5.3 SPEC-DAU(固相萃取法) 26
3.6儀器檢量線之建立 27
3.7尿液方法檢量線之建立 27
3.8 GC/MS回收率之評估 28
3.9 LC/MS2基質效應及回收率之評估 28
3.10穩定度評估 29
3.11真實尿液樣品分析 29
第四章 結果與討論 31
4.1氣相層析質譜分析 31
4.1.1 GC/MS儀器檢量線與方法檢量線 31
4.1.2 GC/MS萃取回收率 33
4.1.3 GC/MS穩定度評估 35
4.2液相層析質譜分析 37
4.2.1 建立新興濫用藥物LC/MS/MS標準圖譜 37
4.2.2 LC/MS/MS儀器檢量線之建立 38
4.2.3 LC/MS/MS方法檢量線之建立 39
4.2.4 基質效應和回收率之評估 40
4.2.5 不同萃取方法之結果與比較 42
4.2.6 穩定度之評估 44
4.2.7 實驗室自建LC/MS/MS資料庫之擴建 44
4.2.8 真實尿液樣本之分析 46
第五章 結論 48
5.1 GC/MS方法確效 48
5.2 LC/MS/MS質譜分析 48
5.3 LC/MS/MS方法確效 50
5.4 真實尿液樣本之分析 52
參考文獻 54
附圖 58
附表 103
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