2011-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649798摘要：緝獲毒品之檢測，待測藥物可能為主成分、濃度較高，且較不需要考慮人體代謝之問題，看似比檢測生物性檢體容易。另一方面，近年來之緝獲藥物逐漸出現多重藥物且採用新興濫用藥物以規避法規刑責之情形，使得其檢驗益形複雜棘手。液相層析/質譜/質譜儀憑藉其高度專一性與游離化技術的進步，加以無氣相層析/質譜儀常需衍生之問題，在過去十年來漸漸嶄露頭角；近年來極致液相層析的技術將液相層析/質譜/質譜儀的應用推至另一境界。液相層析/質譜/質譜儀應用於分析檢體中濫用藥物或代謝物，已有不少報導，但是其用於緝獲毒品之研究或是其廣篩方法之建立仍相當有限。本計畫將針對57種管制與新興濫用藥物和4種常見之併用藥品，開發以極致液相層析搭配三段四極柱串聯式質譜儀（QqQ MS）進行緝獲藥物之快速篩檢和鑑定之檢驗方法。本計畫首先將以標準品建立各待測藥物於10、25、40 eV三種不同撞擊能量下之子離子圖譜資料庫；緝獲藥物於甲醇萃取、離心過濾後，直接注入質譜/質譜儀進行data-dependent acquisition，並透過比對建置之圖譜資料庫，可快速篩出是否含有這些藥物品項。本計畫亦將分別開發適於正、負離子之層析條件，使用具備極致液相層析效能但是管柱壓力為傳統液相層析儀可接受範圍之fused-core管柱，以電灑游離（ESI）與選擇性反應偵測（SRM,或稱為多重反應偵測(MRM)），以層析滯留時間、兩個由母離子（precursor ion）所產生訊號最強的子離子（product ion）、和子離子之相對訊號強度三個條件，對於快篩陽性之樣本或是僅針對某類特定待測藥物之樣本，提供快速、靈敏、且專一性極高之鑑定。本計畫建立之快篩與鑑定分析方法可應用於串聯式質譜儀中最常見的QqQ MS，極致液相層析技術亦能使用於傳統液相層析儀，不僅可大幅降低鑑定分析時間，且可提升對於緝獲毒品之檢測能量。本計畫分析方法具備擴充性，不論日後新增之管制品項或是新興藥物，只要有標準品，皆能擴充質譜/質譜資料庫和依其化學性質套用適合之LC/MS/MS，無須開發新方法，對於研究未來藥物濫用的趨勢或合併使用情形等皆有極大助益。本分析方法樣本前處理極為簡易、快速，儀器分析之專一性極高，無需以其他分析方法再次確認，極適合鑑定查獲藥物之成分組成，提高藥物濫用防制之執行力。<br> Abstract: Comparing with the analysis of illicit drugs in specimens, seized drugs usually contain much higher concentrations of active ingredients and the analysis needs not to consider the metabolism of drugs; however, the use of multiple drugs and the variations on emerging drugs challenge the analysis of seized drugs.The analysis using liquid chromatography/tandem mass spectrometer (LC/MS/MS) is getting popular because of its sensitivity and specificity resulting from the improvement on chromatographic and ionization techniques. LC/MS/MS has been used a lot on analyzing illicit drugs or metabolites in specimens, but its applications on seized drugs are still limited.This project will develop methods on fast screening and identification of 57 controlled drugs and emerging abused drugs plus four usual-combined ingredients using ultra-high performance liquid chromatography (UHPLC) coupled with a triple-quadrupole mass spectrometer (QqQ MS). Spectra of product ions will be collected under three different collision energies for setting up a library. After a simple extraction using methanol, the extracts of ground seized drugs will be directly infused into the QqQ MS for fast screening under data-dependent acquisition and the results will be compared with the spectrum library. The extract can be further analyzed on the UHPLC/MS/MS using electrospray ionization and selected reaction monitoring. Fused-core LC columns will be used for fast separation, which the column backpressure is only about the half of a porous sub-2 m column, and can be utilized on conventional HPLC instruments. The identification of a drug will depend on its retention time, two ion transitions, and the relative signal intensity of the two product ions, which provide unparalleled detection specificity.The methods can be used on the most popular tandem MSQqQ MS, and the fast chromatographic column can be operated on a conventional HPLC; the methods improve throughput by reducing the time for analysis and by making more instruments amenable. The methods can be easily expanded by adding the spectrum of a new chemical into the library or incorporating the chemical into the chromatography as long as the chemical standard is obtainable. This project will provide a simple sample pretrement, fast screening, and highly selective identification on seized drugs.液相層析/質譜/質譜儀極致液相層析電灑游離快速篩檢藥物鑑定質譜資料庫熔融核LC/MS/MSultra-high performance liquid chromatographyelectrospray ionizationfast screeningdrug identificationspectrum libraryfused core