臺灣博碩士論文加值系統

飲用水消毒之益處雖得普遍認可，但過程可能產生消毒副產物對用水民眾健康造成可能危害。鹵乙醯胺類化合物（Haloacetamides，HAcAms）為新興含氮消毒副產物（Nitrogenated DBPs，N-DBPs）較受到關注，HAcAms具有比鹵乙酸、鹵代硝基甲烷等管制或新興含氮消毒副產物更高的細胞毒性和遺傳毒性。過去研究已知特定藥品可經由加氯消毒氧化過程中會生成HAcAms。本研究包含兩目的：其一為為建立HAcAms類化合物之分析方法，本方法包含前處理與後段使用氣相層析質譜儀器（Gas chromatography coupled with mass spectrometry，GC-MS）分析。在多次試驗後選擇鹽析液萃法（Salting-out assisted liquid-liquid extraction）為前處理方法，待測溶液預先添加3 mL之甲基第三丁基醚（Methyl Tert-Butyl Ether）作為萃取溶劑，液萃過程劇烈搖晃兩分鐘後將MTBE取出，共重複進行兩次萃取，收集兩次的萃取液後，以5 N高純氮氣濃縮至0.5 mL；在GC-MS儀器分析方面，設定注射口溫度180°C，管柱烘箱溫度設定為40°C並維持3分鐘，第一階段升溫條件為每分鐘升溫15°C至200°C後維持2分鐘，第二階段升溫條件為每分鐘升溫30°C至250°C後維持溫度1分鐘，整體時間為18.33分鐘，五種鹵乙醯胺（HAcAms）包含一氯、一溴、二氯、一氯一溴、及三氯HAcAm之方法偵測極限分別為4.84、9.71、66.6、67.41及、86.9 µg/L，可再依前處理程序設定之濃縮倍數進一步調整並降低方法偵測極限。本研究第二目的為探究額外氮源對國內大量使用之藥品乙醯胺酚Acetaminophen經由氯胺氧化過程生成HAcAms之影響，批次實驗結果顯示Acetaminophen、氯胺、氨氮、以及酸性pH條件為生成HAcAms四個重要影響因子，結果指出缺乏其中一個實驗條件皆可能顯著抑制Acetaminophen生成HAcAms之生成；除了鹵素的提供外，HAcAms之生成亦需要足夠氮源，但在實驗中可觀察到HAcAms之生成反應對氯與氮的需求有明顯差異，在高氯胺與氮氮濃度條件下實驗反應消耗之氯濃度遠高於所需氮濃度（差異在兩個數量級以上），顯示HAcAms反應過程中足夠的氧化劑破壞Acetaminophen並啟動HAcAms生成為反應重要關鍵，且Acetaminophen本身亦可能提供一定之氮量反應生成HAcAms。以上結果為後續HAcAms污染研究建立適當之分析工具，並提供目前環境常見之氮污染對此類新興污染物生成之可能影響評估參考。

While chlorination has been used worldwide for drinking water disinfection, the disinfection byproducts (DBPs) causes the concern of health risk. Haloacetamides (HAcAms), as emerging nitrogen-containing disinfection byproducts (nitrogenous DBPs, N-DBPs), possess higher cytotoxicity and genotoxicity than regulated haloacetic acids and halonitromethanes. Studies have shown that HAcAms are formed during chlorination and oxidation of specific pharmaceuticals. There are two purposes of this study. One is to establish a method based on salting-out-assisted liquid-liquid extraction followed by gas chromatography-mass spectrometry for determination and quantification of HAcAms-like compounds. By adding 3 mL of methyl tert-butyl ether (MtBE) to the sample (50 mL), HAcAms in the sample were extracted by shaking vigorously for two minutes, followed by collection of the compounds in MtBE extract. The foregoing was repeated and the combined extracts were concentrated to 0.5 mL by nitrogen blowdown. The extract (2 μL) was injected in splitless mode, with a inlet temperature of 180°C. The analytes were separated by using the DB-1701 column. The oven temperature was programmed as follows: initial temperature of 40°C and hold 3 minutes, raised to 200 °C at 15°C/min then hold 2 minutes, then controlled at 250 °C at 30 °C/min. The overall detection time was 18.33 minutes. The method detection limit (MDL) of chlorohaloacetamide, monobromohalide, dichlorohaloacetamide, monochloroammonium bromide, and trichlorohaloacetamide were 4.84, 9.71, 66.6, 67.41, and 86.9 μg/L respectively, which could be further imporved by adjusting the concentration ratio. The other objective of the study is to explore the formation of HAcAms possibly affected by the excess nitrogen source during chloramination of acetaminophen, a widely used drug in Taiwan. The formation of HAcAms were affected by four critical factors including acetaminophen, chloramine, ammonia, and an acidic pH condition, as the absence of anyone alleviated the HAcAms formaiton. Although it is known that halogen and nitrogen supplies are ciritcal for the formation of HAcAms, our results demonstrated the sufficient chloramine for reactions of HAcAm formation from acetaminophen was more important that the amount of nitrogen needed (i.e., the chlorine consumption could be more than two orders of magnitude higher than that of nitrogen). Sufficient oxidant such as chloramine seems to be indispensable to react with acetaminophen and to initiate the formation of HAcAms since acetaminophen plays an important nitrogen source. This research provides not only an analytical method for the following HAcAms studies but also an insight into possible correlation between nitrogen pollution, which is increasingly typical in the environment, and the formation of emergent N-DBPs.

論文審定書 i
致謝 ii
摘要 iii
Abstract v
目錄 vii
圖目錄 x
表目錄 xiii
第一章　前言 1
1.1 研究起緣 1
1.2 研究目的 4
1.3 研究架構 5
第二章　文獻回顧 7
2.1 消毒副產物 7
2.1.1 含碳消毒副產物 10
2.1.2 含氮消毒副產物 12
2.2 含氮消毒副產物HAcAms類化合物介紹 13
2.2.1 HAcAms類化合物毒理危害 15
2.2.2 HAcAms類化合物之前驅物 16
2.2.3 HAcAms之生成機制 17
2.2.4 HAcAms類化合物之流布 21
2.3 新興污染物 30
2.4 藥品及個人保健用品 31
2.4.1 藥品及個人保健食品來源及流布 32
2.4.2 藥品Acetaminophen介紹 34
2.4.3 Acetaminophen作用及危害 36
2.5 HAcAms之分析與前處理 37
2.5.1 前處理方法 38
2.5.2 鹽析液液輔助液液萃取 39
2.5.3 GC-MS儀器分析 40
第三章　研究設備與方法 43
3.1 實驗材料與儀器設備 43
3.1.1 實驗藥品 43
3.1.2 實驗器材與實驗設備 45
3.2 實驗方法 46
3.2.1 完全混合之消毒程序模擬系統 46
3.2.2 消毒劑（氯、氯胺）的製備 49
3.2.3 手持式比色計測試方法 49
3.2.4 HAcAms類化合物樣品前處理與分析 51
3.2.5 相關性分析 52
3.2.6 品質保證與品質管理(QA/QC) 53
3.2.7 藥品生成HAcAms之莫耳轉換率計算 54
第四章　結果與討論 55
4.1 HAcAms分析方法之建立 55
4.1.1 GC-MS第一階段分析方法 55
4.1.2 GC-MS第二階段分析方法 56
4.1.3 GC-MS第三階段分析方法 60
4.2 回收率與方法偵測極限 61
4.3 HAcAm物化參數與分析方法準確度之相關性分析 63
4.4 Acetaminophen與氯胺及氨氮反應生成HAcAms 66
4.5 氯胺濃度之影響 68
4.6 額外氮化物種類之影響 71
4.7 不同pH條件下生成之HAcAms 75
4.8 氯與氮濃度之分析 78
4.9 Acetaminophen與氨氮及氯胺初始濃度比值對生成TCAcAm的影響 84
第五章　結論與建議 86
5.1 結論 86
5.2 建議 87
參考文獻 88