碳酸氫根離子、氯離子及常見水質參數對光催化降解抗癌藥物影響之研究

The Effect of Bicarbonate, Chloride and other Water Parameters on the UV/TiO2 Degradation of Oxazaphosphorine Drugs

莊英志(Ying-Chih Chuang)

指導教授 ： 林郁真

國立臺灣大學/工學院/環境工程學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.10059

摘要

隨著癌症罹患率逐年攀升，抗癌藥物的使用量亦顯著增加，一旦這類藥物排放至環境時，將可能對生態系統及人體健康造成危害。此研究著眼於探討碳酸氫根離子、氯離子及常見水質參數對光催化降解普遍使用環磷醯胺類抗癌藥物Ifosfamide (IFO)及Cyclophosphamide (CP) 之影響。研究結果顯示水中常見的離子存在時(碳酸氫根離子、氯離子、硝酸根離子以及硫酸根離子)，IFO及CP之光催化降解速率趨緩，其半衰期分別為1.2及1.1分鐘；然而水體中離子濃度為1000 mg/L時，IFO 降解半衰期增加2.3至7.3倍之間，而CP之半衰期增加3.2至6.3倍之間 (IFO及CP起始濃度為100 µg/L, pH= 8)。
在UV/TiO2/HCO3−　系統中OH• 與 CO3•−皆為參與IFO 及CP降解之反應物，而CO3•− 相對之反應性較OH• 來得低。雖然碳酸氫根離子存在下會降低目標藥物降解及副產物生成，其新副產物(P11和P12)之生成顯示CO3•−在此系統中產生新的反應路徑；此外，CO3•− 導致IFO 及CP之光催化反應傾向於酮基化作用。而在UV/TiO2/Cl− 系統中，氯離子與OH•反應而抑制其生成量，亦無新的副產物生成，推測其原因為IFO和CP中未具有易與氯衍生之自由基 (Cl•, Cl2•−, ClOH•−)反應之富含電子官能基。
研究顯示碳酸氫根離子或氯離子的存在皆會使目標藥物於UV/TiO2光催化處理六小時後產生較高之毒性。在800 mg/L之碳酸氫根離子與氯離子存在下，IFO降解產物之毒性至高點分別由0.29上升至3.78 (UV/TiO2/HCO3− 系統) 和2.81 (UV/TiO2/Cl− 系統) 毒性單位；CP之毒性亦分別由0.88上升至1.61 (UV/TiO2/HCO3− 系統) 及3.05 (UV/TiO2/Cl− 系統) 毒性單位。
除前述四種不同陰離子外，水中溶解性有機物質亦為對藥物光催化處理效果造成影響之關鍵因子。實驗結果顯示，溶解性有機物與混合藥物皆會使CP之光催化降解速率趨緩，CP降解之半衰期在腐植酸(1 mg-C/L)與稀釋醫院廢水(16.7 mg/L)存在下，分別由1分鐘延緩至6.1分鐘和53分鐘。

關鍵字

環磷醯胺 ； 抗癌藥物 ； 光催化 ； 碳酸氫根離子 ； 氯離子 ； 碳酸根離子自由基 ； 溶解性有機物

並列摘要

Cytostatic drugs are used increasingly for cancer thermotherapy treatment, and they pose potential risk to ecosystems and human health once released to the aquatic environments. This study investigated the effect of bicarbonate, chloride and other water parameters on the UV/TiO2 degradation of the two frequently prescribed oxazaphosphorine drugs (ifosfamide (IFO) and cyclophosphamide (CP)). Results showed that common anions HCO3−, Cl−, NO3−, SO42− in water bodies lead to the lower degradation efficiency of IFO and CP. The half-lives of IFO and CP were 1.2 and 1.1 minutes, but were increased 2.3−7.3 times and 3.2−6.3 times, respectively in the presence of these anions (initial compound concentration = 100 µg/L, pH = 8, anions concentration = 1000 mg/L).
In UV/TiO2/ HCO3− system, the results indicated OH• and CO3•− participated in IFO and CP degradation in UV/TiO2/HCO3− system; CO3•− is less reactive towards IFO and CP compared to that of OH•. Although the presence of HCO3− resulted in lower degradation rate and lower byproduct formation of IFO and CP, two new byproducts (P11 and P12) were produced and detected, indicating that CO3•− would lead to the additional pathway in the system. In addition, results showed that photocatalytic reaction of IFO and CP with CO3•− is likely to resulted in a preferred ketonization pathway. In UV/TiO2/Cl− system, less degradation of byproduct was observed because chloride could react with OH• and result in less available OH• in the system. No new byproducts were observed in this system. It’s likely due to the fact that IFO and CP don’t have electron-rich functional groups which Cl-derived radicals (such as Cl•, Cl2•−, ClOH•−) would prefer to react with.
The presence of bicarbonate or chloride in UV/TiO2 treatment leads to a higher toxicity within six hours of reaction time. In the presence of 800 mg/L bicarbonate and chloride, the highest toxicity unit of IFO increased from 0.29 to 3.78 (UV/TiO2/ HCO3− system) and to 2.81 (UV/TiO2/Cl− system), respectively. In the case of CP, it increased from 0.88 to 1.61 (UV/TiO2/HCO3− system) and to 3.05 (UV/TiO2/Cl− system).
Besides HCO3−, Cl−, NO3−, SO42−, dissolved organic matters (DOM) also plays a crucial role in the overall CP removal in the real wastewaters. DOM and pharmaceutical mixture slowed down the photocatalytic degradation rate of CP; half-life of CP was increased from one minute (in DI water) to 6.1 minutes in spiked fulvic acid (1 mg-C/L) and 53 minutes in diluted hospital wastewaters (16.7 mg-C/L).

並列關鍵字

Ifosfamide ； cyclophosphamide ； oxazaphosphorine drugs ； photocatalytic oxidation ； bicarbonate ； chloride ； carbonate radical ； dissolved organic matter

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