亞硝胺類化合物（Nitrosamine）為近年來新興含氮消毒副產物（Nitrogenous disinfection byproducts，NDBPs）中備受關注的物種之一，由於產業及人類生活模式改變使大量新興有機污染物衝擊自然水體，藥品及個人保健用品（Pharmaceuticals and personal care products, PPCPs）因不當棄置且無法被人體完全代謝而進入水及廢污水處理系統，不僅無法有效的被去除，更可能與氯（Chlorine）、氯胺（Chloramine）以及臭氧（Ozone）等氧化劑反應產生消毒副產物，亞硝胺即為其中之一。本研究選擇四種具特定官能基的藥品作為前軀物，具胺基及苯環的氯苯那敏（Chlorpheniramine）及多西拉明（Doxylamine）;具胺基及硝基的尼唑替丁（Nizatidine）及雷尼替丁（Ranitidine），模擬一階段臭氧消毒程序以及二階段前氧化（臭氧）後消毒（次氯酸鈉）程序針對水體pH值、臭氧劑量、前軀物劑量以及不同氮化物添加等項目，並分析八種亞硝胺類化合物包含N-Nitrosodimethylamine（NDMA）、N-Nitrosomethylethylamine（NMEA）、N-Nitrosopyrrolidine（NPyr）、N-Nitrosodiethylamine（NDEA）、N-Nitrosopiperidine（NPip）、N-Nitrosomorpholine（NMor）、N-Nitrosodi-n-propylamine（NDPA）以及N-Nitrosodi-n-butylamine（NDBA）之生成量，後續將結果與一階段次氯酸鈉消毒試驗（王氏, 2016）以及二階段前氧化（次氯酸鈉）後消毒（次氯酸鈉）試驗（許氏, 2016）比較。

研究結果顯示，所有試驗中皆以NDMA為主要生成物種，在以Chlorpheniramine及Doxylamine為前軀物時有NMEA生成，雖然在一階段及二階段實驗結果皆觀察到生成但生成量無顯著差異，說明在以Doxylamine為前軀物時，NMEA生成應與臭氧氧化反應有關。Ranitidine擁有強親電的呋喃環使NDMA轉換率遠高於相似結構的Nizatidine以及具胺基及苯環的Chlorpheniramine及Doxylamine，說明藥品前軀物的結構特徵同時影響亞硝胺生成物種以及轉換率。水體pH值的影響與藥品前軀物之解離常數（pKa）有關，上述兩者決定藥品前軀物的質子化程度，結果顯示若藥品前軀物質子化程度越低則有助於NDMA轉換率提升。一階段及二階段試驗結果皆顯示，臭氧與藥品前軀物之莫耳比例（O3/PPCPs）越高NDMA轉換率則越低，且即便在原水被不同氮化物（氨氮、硝酸鹽及亞硝酸鹽）污染情境下仍可有效降低NDMA轉換率，若原水含有特定種類前軀物亞硝酸鹽仍可因亞硝化反應而刺激NDMA生成。
一階段消毒（次氯酸鈉或臭氧）試驗以及二階段前氧化（次氯酸鈉或臭氧）後消毒（次氯酸鈉）試驗結果皆顯示，臭氧作為消毒劑或前氧化劑皆能有效降低藥品前軀物之NDMA轉換率以及亞硝胺物種生成，為實務應用有效降低亞硝胺類化合物生成的操作程序。

Nitrosamine are a group of emerging nitrogenous disinfection byproducts (N-DBPs) of concern in the field of deinking treatment. Given the impact of industrialization on life changing, the adverse influences of a number of organic emerging contaminants (ECs) into the environment have been frequently reported. One notorious example is the release of pharmaceuticals and personal care products (PPCPs) into the drinking water treatment plants (DWTPs) and wastewater treatment plants (WWTPs) via metabolism byproducts of human and animals and improper disposal of wastes containing these ECs. Certain amine-based pharmaceuticals have been demonstrated to form nitrosamine during chlorination, chloramination, or ozonation. In this study, four different pharmaceuticals including chlorpheniramine, doxylamine, nizatione and ranitidine, have been chosen as the precursor considered their potentials to form nitrosamines (e.g., containing functional groups including amines, nitro, or phenyl groups). The effects of different disinfection approaches (with/without pre-oxidation), pH value, ozone dose, precursor dose, and additional inorganic nitrogen on the nitrosamine formation during ozonation of pharmaceuticals were investigated. The nitrosamines of interest included N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine(Npyr), N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (Npip), N-nitrosomorpholine (Nmor), N-nitrosodi-n-propylamine (NDPA) and N-nitrosodi-n-butylamine (NDBA). In the results, NDMA was the main species during ozonation of four pharmaceuticals. While chlorpheniramine and doxylamine were employed as the precursors, the formation of NMEA was observed. NMEA was observed both during ozonation and during pre-ozonation followed by chlorination. However, the molar conversion rates were different between these two approaches. Ranitidine was the precursor with the highest NDMA molar conversion rate, possibly due to its furan functional group, suggesting the importance of the molecular structure of a pharmaceutical for predicting its nitrosamine formation. Limited protonation of a pharmaceutical inhibited its NDMA formation. During ozonation or pre-ozonation followed by chlorination, the NDMA mloar conversion rate increased with the O3/PPCP molar ratio. In most cases, the presence of excess inorganic nitrogen (including ammonium, nitrite and nitrate) did not significantly changed the NDMA formation during ozonation, whereas high nitrite levels might still enhance the NDMA formation during ozonation of certain pharmaceuticals such as ranitidine in this study. The results provided insight into the nitrosamine formation during ozonation of pharmaceuticals, showing that compared to chlorination, ozonation could be a better approach to control the NDMA or other nitrosamine formation during disinfection of pharmaceuticals.

論文審定書 i
致謝 ii
摘要 iii
Abstract v
目錄 vii
圖目錄 xi
表目錄 xiv
第一章 前言 1
1.1 研究緣起 1
1.2 研究目的 3
1.3 研究架構 5
第二章 文獻回顧 7
2.1 含氮消毒副產物 8
2.2 亞硝胺類化合物 10
2.2.1 亞硝胺類化合物物化特性 12
2.2.2 亞硝胺類化合物毒理危害 14
2.2.3 亞硝胺類化合物之規範 16
2.2.4 亞硝胺類化合物之生成機制 18
2.2.5 亞硝胺類化合物之前軀物 22
2.3 藥品及個人保健用品 27
2.3.1 藥品及個人保健用品來源及流佈 28
2.3.2 藥品與亞硝胺類化合物之轉換機制 29
2.4 臭氧 31
2.4.1 臭氧之物化特性 31
2.4.2 臭氧之氧化機制 33
第三章 實驗方法 35
3.1 實驗藥品與儀器設備 35
3.1.1 實驗藥品 35
3.1.2 實驗設備與儀器 38
3.2 實驗方法 39
3.2.1 臭氧曝氣效率 39
3.2.2 氧化劑（次氯酸鈉）製備 39
3.2.3 藥品前軀物 40
3.3 實驗條件 41
3.3.1 前軀物劑量試驗 41
3.3.2 臭氧劑量試驗 41
3.3.3 氮源添加試驗 42
3.3.4 前臭氧、後加氯試驗 42
3.4 實驗樣品分析 43
3.4.1 樣品前處理 43
3.4.2 亞硝胺類化合物分析 44
3.4.3 儀器分析檢量線 45
3.4.4 偵測極限 46
3.4.5 回收率 47
3.4.6 自由餘氯分析 47
3.4.7 水中臭氧分析 48
3.5 亞硝胺類化合物莫耳轉換率 48
第四章 結果與討論 49
4.1 臭氧接觸試驗 50
4.2 pH值對藥品前軀物生成NDMA之影響 53
4.3 臭氧劑量對藥品前軀物生成NDMA之影響 56
4.4 藥品前軀物濃度生成NDMA之影響 60
4.5 臭氧與藥品之莫耳比例生成NDMA之影響 64
4.6 不同氮源添加對藥品前軀物生成NDMA之影響 67
4.7 亞硝酸鹽對Ranitidine經臭氧氧化生成NDMA之影響 71
4.8 多種亞硝胺類化合物生成 73
4.9 藥品經不同程序之NDMA轉換率比較 80
第五章 結論與建議 84
5.1 結論 84
5.2 建議 86
參考文獻 88

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