隨著時代的變遷，人們追求生活的便利性，進而促使經濟快速發展，伴隨而來的是環境污染，而且變成世人不得不面對的問題，然而還有一些污染物是沒被大眾察覺及看見，卻忽略了它所帶來給環境和人體的影響及危害，那就是新興污染物。所謂新興污染物，其實都存在你我生活中，本研究以藥品和個人護理產品(PPCPs)類別中的糖尿病用藥二甲雙胍(Metformin)和止痛用藥乙醯胺酚(Acetaminophen)為目標污染物，使用氣相層析質譜儀(GC/MS)和液相層析串聯質譜儀(LC/MS/MS)分析，找尋無須衍生化及萃取的前處理方式，樣品僅簡單過濾即進行儀器分析並能達到ppb濃度分析等級。本研究主軸主要分為四個部分：首先是蒐集相關的文獻及資料；其次是使用儀器針對藥品進行定性分析，並透過不同文獻及公開資料庫交叉比對，確認定性的結果；第三部分則針對分析方法進行深度優化，包括層析條件、質譜的離子源和化合物的個別優化；最後則依照環檢所公告的環境檢驗方法偵測極限測定指引，得到Metformin在GC/MS的方法偵測極限是12.95 ppm，在LC/MS/MS則是0.30 ppb；而Acetaminophen在GC/MS的方法偵測極限是1.65 ppm，在LC/MS/MS則是0.88 ppb。使用標準品建立檢量線後，Metformin與Acetaminophen在GC/MS的線性R2分別是0.9996及0.9998；Metformin與Acetaminophen在LC/MS/MS的線性R2則是0.9994和0.9998，確認兩種分析物皆可經由GC/MS和LC/MS/MS得到極佳線性結果，且本研究亦採集環境水體(高屏溪原水、澄清湖原水、淨水廠進水)套用此檢量線進行測試，雖然結果指出環境水體中不存在這些藥品濃度，但額外加藥可有效檢出且雖然有基質干擾，仍可藉由調整特徵峰滯留時間的方式來避開此問題。整體而言，本研究確認Metformin和Acetaminophen皆可藉由GC/MS和LC/MS/MS的分析，在定性及定量上得到高準確性及高精密性，其中又以Metformin具有較佳親水性(辛醇水分配常數，log Kow= -2.64)，因此非常適合使用LC/MS/MS進行分析。

With the changes of the times, people pursue a convenient life and promote the rapid development of the economy. Unfortunately, environmental pollution has become a problem everyone has to face. Certain pollutants have not been carefully noticed, ignoring their negative impacts on the environment and public health. One typical example is the contaminant of emerging concern(CECs). With limited attention and investigation, CECs exist indeed in our lives. The objective of this study is to investigate the feasibility of analyzing the diabetes drug, metformin, and the analgesic drug, acetaminophen, the two most widely used pharmaceuticals and personal care products (PPCPs), by using the gas chromatography coupled with mass spectrometry (GC/MS) and liquid chromatography coupled with triple quadrupole mass spectrometry (LC/MS/MS) without extraction and derivatization. The sample just needs filtration before the instrumental analysis to reach a detection limit in a ppb-level range. There are four stages in this study. First, relevant literature and data were collected and reviewed. Next, two instruments were operated for the qualitative analyses of two compounds to confirm the results with cross-comparison of different literature and public databases. Thirdly, the analytical methods such as the parameters used for separation and detection were optimized. Finally, the experiment method detection limits (MDL) of two compounds were determined following the standard method by the National Institute of Environmental Analysis (NIEA). The MDL of metformin in GC/MS was 12.95 ppm, while the MDL in LC/MS/MS was 0.30 ppb. The MDL of acetaminophen in GC/MS was 1.65 ppm, as that by LC/MS/MS is 0.88 ppb. The coefficients of determination of metformin and acetaminophen were 0.9996 and 0.9998 in GC/MS, and 0.9994 and 0.9998 in LC/MS/MS, respectively. Both GC/MS and LC/MS/MS exhibited excellent linearity for the relationships between the concentration and response. The field samples from Gaoping River, Cheng Ching Lake, and an influent sample of a drinking water treatment plant were collected as well as applied to test the established analytical methods. Although the presence of two compounds in the field samples were not detected, injecting standards in the field samples were successfully detected. The matrix interference occurred but could be avoided by optimization of the methods (adjustment of the retention times). In conclusion, this study confirms that both metformin and acetaminophen can be qualitatively and quantitatively analyzed by using GC/MS and LC/MS/MS without derivatization, as sufficiently high accuracy and precision levels are still achievable. Moreover, metformin is more hydrophilic (octanol-water partition coefficient, log Kow= -2.64) than acetaminophen, resulting in it more suitable for the LC/MS/MS analysis.

論文審定書 i
摘要 ii
Abstract iv
目錄 vii
圖目錄 xi
表目錄 xiv
第一章　前言 1
1.1 研究起緣 1
1.2 研究目的 3
第二章　文獻回顧 4
2.1 新興污染物 4
2.1.1 定義 4
2.1.2 緣起 5
2.1.3 風險 6
2.1.4 現有處理程序及相關技術 7
2.2 藥物及個人保健用品PPCPs 8
2.2.1 來源、流布及列管 8
2.2.2 藥品Metformin 11
2.2.3 藥品Acetaminophen 12
2.2.4 藥品Metformin與Acetaminophen使用情形 13
2.3 Metformin和Acetaminophen分析方法 14
2.3.1 層析分離技術 14
2.3.2 質譜偵測技術 16
2.3.3 氣相層析質譜儀(GC/MS) 19
2.3.4 液相層析串聯質譜儀(LC/MS/MS) 23
第三章　研究方法與設備 29
3.1 研究方法 29
3.2 研究設備與器材 30
3.2.1 儀器設備 30
3.2.2 實驗器材 30
3.3 研究藥品與溶劑 31
3.4 標準品/檢量線配置 31
3.5 初始儀器參數 35
3.5.1 GC/MS初始儀器參數 35
3.5.2 LC/MS/MS初始儀器參數 36
3.6 定性方法 37
3.7 方法偵測極限 37
3.8 定量方法 38
3.9 環境水體場址選定與說明 38
第四章　結果與討論 40
4.1 定性分析 40
4.1.1 Metformin定性比對 40
4.1.1.1 GC/MS結果 40
4.1.1.2 LC/MS/MS結果 42
4.1.2 Acetaminophen定性比對 44
4.1.2.1 GC/MS結果 44
4.1.2.2 LC/MS/MS結果 45
4.2 GC/MS方法優化建立 48
4.2.1 層析優化 48
4.2.1.1 移動相的選擇 48
4.2.1.2 汽化管(Liner)的選擇 48
4.2.1.3 樣品溶劑的選擇 48
4.2.1.4 管柱的選擇 48
4.2.1.5 柱溫箱等溫度的優化 49
4.2.1.6 柱溫箱起始溫度的優化 51
4.2.1.7 柱溫箱升溫速率梯度的優化 53
4.2.1.8 注射口溫度的優化 55
4.2.2 質譜優化 56
4.2.2.1 MS Source的溫度選擇 56
4.2.2.2 MS Quadrupole的溫度選擇 56
4.2.3 GC/MS優化後Metformin與Acetaminophen的SIM參數 57
4.3 LC/MS/MS方法優化建立 58
4.3.1 層析優化 58
4.3.1.1 移動相的選擇 58
4.3.1.2 管柱的選擇 58
4.3.1.3 流速的選擇 58
4.3.1.4 溫度的選擇 58
4.3.1.5 緩衝溶液(Buffer)的選擇 59
4.3.1.6 酸鹼值的選擇 59
4.3.1.7 移動相梯度(Gradient)的優化 59
4.3.2 離子源優化 62
4.3.2.1 Nebulizer pressure的優化 62
4.3.2.2 Drying gas flow的優化 63
4.3.2.3 Drying gas temperature的優化 64
4.3.3 化合物質譜優化 65
4.3.3.1 Collision energy的優化 65
4.3.3.2 Fragmentor的優化 66
4.3.4 LC/MS/MS優化後Metformin與Acetaminophen的SIM參數 68
4.4 方法偵測極限與進行儀器分析的檢量線 69
4.4.1 方法偵測極限 69
4.4.2 GC/MS進行儀器分析的檢量線 70
4.4.3 LC/MS/MS進行儀器分析的檢量線 71
4.5 環境水體分析結果 72
4.5.1 高屏溪水分析結果 72
4.5.2 澄清湖水分析結果 74
4.5.3 淨水廠進水分析結果 76
第五章　結論與建議 79
5.1 結論 79
5.2 建議與未來方向 81
參考文獻 82

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