多重藥物氯化反應及其轉化產物之研究

Transformation of Multiple Pharmaceuticals by Chlorination Procedure

劉譿ᡒ(Hui-Sz Liu)

指導教授 ： 胡景堯

臺北醫學大學/公共衛生暨營養學院/公共衛生學系暨研究所/碩士(2015年)

摘要

隨著醫學的進步，越來越多合成藥物被開發及使用,這些化學物質會隨著人體代謝排泄或是不當丟棄而進入環境中，當污水廠無法完全去除這些物質時，即有可能會隨著放流水排放而導致環境受汙染。雖然在污水系統及環境中所偵測到的藥物濃度約ng/L 至 ?慊/L，但已有許多研究證實暴露在這些藥物下會對水生生物造成負面影響。
氯化反應在水處理中是最常應用的消毒方式。當氯氣通入水中會水解成次氯酸，由於次氯酸本身為弱酸因此在水中又會進一步解離。氯本身是一種強氧化劑，會與水中的有機物質反應，特別是與帶有苯環、胺基或是雙鍵的有機物反應。
先前雖然已有許多針對單一藥物的氯化反應研究，但實際污水及環境中卻有多中藥物同時存在。因此本研究選擇三種不同類型、被廣泛使用且在污水及環境中檢出頻繁的藥物，分別為乙醯胺酚(Acetaminophen)、磺胺甲噁唑(Sulfamethoxazole)及雙氯芬酸(Diclofenac) 探討多重藥物的氯化反應，並研究加氯劑量及酸鹼值的影響。
實驗結果顯示，酸鹼值會顯著影響藥物的去除。Sulfamethoxazole和Diclofenac在酸性環境下的去除率較中性及鹼性環境佳，但Acetaminophen則是在鹼性環境下有最好的去除效果，類似的結果也在其他研究中有觀察到。生成產物則是利用極致液相層析儀串聯飛行時間串聯式質譜儀(UPLC-Q-TOF-MS)進行鑑定，在單一藥物系統下反應後發現Acetaminophen有兩種轉化產物生成、Sulfamethoxazole有七種產物，而Diclofenac則是有六種產物。這些產物有些已在先前研究中有發現，有些則還是未知產物。而在多重藥物系統中，發現有新的產物是在單一藥物系統中沒有發現的，這些新產物可能是不同的轉化產物或藥物結合而成。根據這個結果，多重藥物的氯化反應可能會生成更多的轉化產物，其反應機制可能也比原先預期來得複雜。

關鍵字

乙醯胺酚 ； 磺胺甲噁唑 ； 雙氯芬酸 ； 氯化反應 ； 極致液相層析儀串聯飛行時間串聯式質譜儀

並列摘要

With the advance of medicine, more and more synthetic drugs have been invented and used. These chemicals will enter the environment because of human excretion and improper disposal. The waste water treatment plant cannot remove the pollution completely, and our environments will be contaminated by these chemicals. Although their concentrations in the wastewater systems and environments usually range from nanogram per liter to microgram per liter level, many studies show that exposure to pharmaceutical substances can result in adverse effects to aqueous species.
Chlorination procedure is the most commonly applied disinfection methods for water and wastewater treatments due to its low cost. Chlorine gas hydrolyzes in water to form hypochlorous acid (HOCl), while HOCl is a weak acid which dissociates in aqueous solutions. Chlorine is a strong oxidant that reacts with the organic matter in water; especially reacts with organic compounds containing aromatic system, neutral amines and double bonds.
Many researches have been done about the removal characteristics of single pharmaceutical compound by chlorine. However, multiple pharmaceuticals may be present in wastewater or in environments. In this study, we selected three different pharmaceuticals, Acetaminophen, Sulfamethoxazole and Diclofenac, which are frequently used and be often detected in wastewater and surface water to investigate their transformation by chlorination. The effects of dose of chlorine and pH value were also investigated.
The results indicate that pH value significantly influenced the transformation of all the three pharmaceuticals. The transformation of Sulfamethoxazole and Diclofenac in acidic condition was faster than that in neutral or alkali conditions, while the transformation of Acetaminophen in alkali condition was more effective. Similar results have been observed in previous studies. UPLC-Q-TOF MS were used to identify transformation products. In single pharmaceutical system, we find two products of Acetaminophen, 7 products of Sulfamethoxazole and 6 products of Diclofenac. Some of these products were also found in previous study, but few of them are new. In multiple pharmaceuticals system, we find two products which were not found in single pharmaceutical system. These products may be polymers of the transformation products and pharmaceuticals. Therefore, chlorination of multiple pharmaceuticals may form more products and be more complicated than that of signal pharmaceutical.

並列關鍵字

Acetaminophen ； Sulfamethoxazole ； Diclofenac ； chlorination ； UPLC-Q-TOF-MS

參考文獻

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