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  • 學位論文

以極致液相層析/串聯式質譜儀快篩與確認多重管制藥物

Fast Screening and Confirmation of Multiple Control Drugs Using Ultra-High Performance Liquid Chromatography/Tandem Mass Spectrometry

指導教授 : 陳家揚

摘要


藥物濫用造成社會問題由來已久,尤其是未納入管制的新興濫用藥物諸如色胺類與苯乙胺等,使得藥物濫用問題日益複雜。本研究針對61種藥物包括管制藥物、新興濫用藥物與常見併用藥物,利用極致液相層析串聯三段式四極柱質譜儀開發快篩與確認方法。本研究選用Ascentis Express RP-Amide管柱 (50 * 2.1 mm, 2.7 μm) 搭配由乙腈與10 mM 醋酸胺溶液所組成之移動相,針對其中53種易於形成正離子之藥物進行層析,層析時間包括管柱再平衡共費時8.5分鐘;其餘8種易形成負離子之藥物,則使用Fortis H2o管柱 (30 * 2.1 mm, 1.7 μm) 並利用甲醇與0.5%乙酸組合作為移動相進行層析,層析時間包括管柱再平衡僅需時6.6分鐘。本研究使用胃乳片與amoxicillin粉末作為模擬基質,利用甲醇進行超音波萃取後,經高速離心並過濾再行上機分析。其中51種藥物在游離化的過程中,其訊號受到基質干擾之比率小於30%。本研究針對偵測極限與基質效應,比較電灑游離法與大氣壓光游離法二種游離源之表現,其結果顯示電灑游離法在二方面皆優於大氣壓光游離法。本研究並使用Chromalynx軟體建立濫用藥物資料庫;Chromalynx軟體原設計用於液相層析串聯飛行時間質譜儀,針對未知化合物進行快篩,本研究將之用於液相層析串聯三段式四極柱質譜儀,結果顯示成功的資料庫比對主要受到層析滯留時間、待測物分子量與待測物碎片形式所影響。

並列摘要


The problem of drug abuse has been a long-term concern by societies, especially the increasing use on emerging drugs like tryptamines and psychedelic phenethylamines, which have not been included as control drugs. We developed a screening and confirmatory method for detecting 61 drugs including control drugs, emerging abused drugs and common combined-use drugs, with an ultra-high performance chromatography/triple-quadrupole mass spectrometer (UHPLC-QqQMS). Fifty three drugs forming positive ions were separated on an Ascentis Express RP-Amide column (50 * 2.1 mm, 2.7 μm) within 8.5 min including re-equilibrium with the mobile phase composed of acetonitrile and 10 mM ammonium acetate. The separation of eight drugs forming negative ions was achieved on a Fortis H2o column (30 * 2.1 mm, 1.7 μm) and took only 6.6 min with the mobile phase containing methanol and 0.5% acetic acid. In this study, we use antacid tablets and amoxicillin powder as the simulated matrixes; samples were extracted with sonication in methanol, then were centrifuged and filtered before injecting onto the instrument. The influence of matrix components to the ionization efficiency on 51 analytes was lower than 30%. We also compared the detection sensitivity and matrix effect between electrospray ionization (ESI) and atmospheric photoionization (APPI), and ESI was found to be better than APPI. The Chromalynx software, which was designed for fast screening of unknown compounds on a LC-time of flight-MS, was studied on the LC-QqQMS for this purpose. Retention time, analyte molecular weight, and patterns of fragmentation played crucial roles in a successful matching of library search.

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