質譜儀 (Mass Spectrometry) 已是目前世界上公認最靈敏的分析工具之一。而大氣游離質譜法 (Ambient Ionization Mass Spectrometry, AIMS) 是一種新穎的質譜技術，可以直接分析樣品的自然狀態，不論是固體樣品、液體樣品，甚至材料都可以直接分析；比起傳統的質譜分析，它不需要經過複雜的樣品前處理，分析時間短，僅需數十秒即可完成一次分析，對於一些具急迫性或大量樣品需即時分析時，就能展現十分強大的能力。在臨床上，針對急性中毒病患必須及時給予高效率之緊急處置，以降低其死亡率和減少併發症發生率。然而，透過病史和身體檢查等傳統策略在鑑別這些毒物方面並非絕對可靠。此外，在常規的實驗室試驗 (如：氣相層析質譜法或液相層析質譜法) 中進行之樣品前處理皆過於耗時，不適用於急診。因此近幾年來，隨著大氣游離質譜法的發展迅速，應用於臨床檢驗上的相關研究更不計其數。像是紙灑游離法 (Paper Spray Ionization, PSI ) 可對濾紙上的乾血漬直接進行分析；探針電噴灑游離法 (Probe Electrospray Ionization, PESI ) 可直接對於大鼠肝臟進行分析；熱脫附電噴灑游離法 (Thermal Desorption-Electrospray Ionization, TD-ESI) 可直接於唾液中分析殘餘農藥等。
第一部分- 利用電噴灑雷射脫附游離質譜法 (Electrospray Laser Desorption Ionization Mass Spectrometry, ELDI/MS) 快速分析揮發性較低之毒性草藥成分，並可利用主成分分析(Principal Components Analysis, PCA) 軟體來快速辨識易混淆有毒草藥及有毒草本植物。
第二部分- 利用TD-ESI/MS結合實驗室建立之316種台灣常見農藥毒物資料庫，可對洗胃液樣品做非標的篩選分析 (Untargeted Screening)，在此研究中，共分析了9起真實農藥自殺中毒案例病人之洗胃液，其中包括巴拉刈 (除草劑)、陶斯松 (有機磷類)、納乃得 (胺基甲酸脂類)、百滅寧 (除蟲菊精類)。透過實驗室自訂的一套標準分析作業流程，可在最短時間內提供正確毒物資訊，讓急診醫師可以及時對病人做正確的急救與治療。

With the rapid development of ambient ionization mass spectrometry (AIMS) in recent years, there are more and more applications about how to use this technique for medical purposes have been published. In analytical purpose, there are pros and cons of the traditional mass spectrometer and AIMS. Although the previous ones (such as gas chromatography mass spectrometry and liquid chromatography mass spectrometry) take time to identify the materials, it can measure their quantity precisely. On the other hand, AIMS is on the contrary. It can quickly distinguish the types of materials, while, it can't estimate the exact quantity of them. However, when it comes to urgent medical applications, the latter is more suitable than the formers. In clinical, although the formers are more precise compared to the medical history and physical examination, the sample preparation procedures are time-consuming. Hence, it is challenging to be applied in the emergency. On the contrary, compared to the formers, AIMS can analysis directed toward the material's original status (solid or liquid), it also requires less time and less complicated processes for sample preparation. Therefore, it can reduce the mortality rate and some sequential side effects for poisoned patients who need high-accuracy treatments. Accordingly, AIMS is widely applied in urgent situations in recent years. For instance, paper spray ionization (PSI) is used to analyze the dry blood spots on the filter paper, probe electrospray ionization (PESI) can directly examine the livers of mouse, and thermal desorption electrospray ionization (TD-ESI) can directly detect the residual part of pesticide in saliva. Hence, based on the AIMS method, this dissertation focus on two parts:
Firstly, using electrospray laser desorption ionization mass spectrometry (ELDI/MS) to analyze toxic herbal ingredients of low volatility. And with assistance of the PCA software, to identify the confusing toxic herbal medicine and toxic herb.
Second, using the TD-ESI/MS to combine the database of 316 types of pesticide poison in Taiwan, we can do untargeted screening to gastric lavage samples. In this research, we analyzed nine different sample of gastric lavage samples, which came from the patients who committed suicide with pesticide, including paraquat (Herbicides)、chlorpyrifos (Organophosphates)、methomyl (Carbamates)、permethrin (Pyrethroid). With the established standard operating procedures (SOP), we can provide the exact information of poison within a short time, allow the emergency doctor to treat patients quickly and correctly.

目錄
論文審定書 i
謝　誌 ii
中文摘要 iv
Abstract v
目錄 vii
圖目錄 x
表目錄 xvi
縮寫用語對照表 xviii
縮寫用語對照表 (續) xix
第一章、緒論 1
1.1 前言 1
1.2 大氣游離質譜法的發展 3
1.2.1 直接電噴灑探針 (Direct Electrospray Probe, DEP) 4
1.2.2 脫附電噴灑游離法 (Desorption Electrospray Ionization, DESI) 5
1.2.3 即時直接分析法 (Direct analysis in real time, DART) 6
1.3 大氣游離質譜法於臨床檢驗之應用 7
1.3.1 紙灑游離法 (Paper Spray Ionization, PSI) 8
1.3.2 探針電噴灑游離法 (Probe Electrospray Ionization, PESI) 9
1.3.3 快速蒸發游離質譜法 (Rapid Evaporative Ionization Mass Spectrometry, REI/MS) 10
1.3.4 觸灑游離法 (Touch Spray Ionization, TSI) 11
1.3.5 熱脫附電噴灑游離法 (Thermal Desorption-Electrospray Ionization, TD-ESI) 12
1.4 論文目標 13
第二章、以電噴灑雷射脫附游離法快速鑑別有毒中草藥之毒性成份 14
2.1 前言 14
2.2 實驗部分 16
2.2.1 實驗樣品與試劑 16
2.2.2 儀器設備 23
2.2.3 主成分分析軟體 27
2.3 結果與討論 28
2.3.1 毒性成份標準品之分析結果並建立方法資料庫 28
2.3.2 真實樣品之分析流程 30
2.3.3 比較不同樣品處理方式之分析結果 31
2.3.4 探討不同溶劑之萃取效益 34
2.3.5 探討分析方法之重複性 (Repeatability) 與再現性 (Reproducibility) 37
2.3.6 定量分析之探討 38
2.3.6 以ELDI/MS結合多變量分析快速辨識易混淆之有毒中草藥與有毒草本植物 40
2.4 結論 42
第三章、以熱脫附電噴灑游離法於病人洗胃液中快速鑑別農藥中毒成份 43
3.1 前言 43
3.2 實驗部分 46
3.2.1 實驗樣品與試劑 46
3.2.2 儀器設備 48
3.2.3 建立316種農藥毒物資料庫 (TD-ESI/MS ultivo) 54
3.2.4 建立分析的標準作業流程於急診真實案例中快速鑑別農藥中毒成份 56
3.3 農藥自殺中毒病人之洗胃液真實案例分析 61
3.3.1 巴拉刈 (除草劑農藥) 中毒案例 61
3.3.2 疑似巴拉刈 (除草劑農藥) 中毒案例 72
3.3.3 陶斯松 (有機磷類農藥) 中毒案例 78
3.3.4 納乃得 (胺基甲酸脂類農藥) 中毒案例 86
3.3.5 百滅寧 (除蟲菊精類農藥) 中毒案例 97
3.4 結論 109
第四章、總結 111
第五章、參考文獻 138

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