抗癌藥物在水體環境中的光降解：環磷醯胺及5-氟尿嘧啶

Abstract

本研究主要探討兩種廣泛使用的抗癌藥物環磷醯胺(cyclophosphamide)及5-氟尿嘧啶(5-fluorouracil)在水體環境中的光降解宿命。實驗方法為使用日光模擬器 (氙弧燈，765 W/m2，波長大於 290 nm)模擬日光照射下目標化合物的直接、間接及環境水體中的光降解。實驗室的合成水質為單獨及綜合探討三種光降解前趨物質的影響，包括溶解性有機物質(dissolved organic matter, DOM)、硝酸鹽(nitrate)及碳酸氫鹽(bicarbonate)，另外選擇四個臺灣北部都會區的表面水體做為代表環境水體光降解的不同基質。 研究結果顯示環磷醯胺無法進行直接光降解，然而5-氟尿嘧啶具有直接光降解的能力，其初始濃度5至500 μg/L之半生期為45.5 ± 5.1至74.9 ± 17.8小時。DOM、硝酸鹽及碳酸氫鹽對於環磷醯胺及5-氟尿嘧啶的光降解皆具有重要性。經由這三種前趨物質分別產生的氫氧自由基 (hydroxyl radical, •OH)及單重激發態氧 (singlet oxygen, 1O2)皆能與環磷醯胺及5-氟尿嘧啶進行反應，然而激發態溶解性有機物質(triplet excited states of dissolved organic matter, 3DOM*)及碳酸自由基(carbonate radical, •CO3-)只能與5-氟尿嘧啶進行反應。四個表面水體的基質雖然相當複雜，但整體光降解趨勢大致與實驗室合成水質得到的結論一致，可說明本研究所選擇的三種前趨物質即為在水體環境中主要影響光降解的物質。環磷醯胺及5-氟尿嘧啶在景美溪水樣中的光降解半生期分別為50.1 ± 0.5及9.2 ± 0.7小時，經由本研究可說明環磷醯胺較具持久性而且可能容易殘留在自然水體環境裡。

This work aimed to investigate the photodegradation of two widely used anticancer drugs, cyclophosphamide and 5-fluorouracil. Direct, indirect and surface water photolysis experiments were processed by sunlight simulator (Xenon–arc lamp, 765 W/m2, wavelength above 290 nm). Three precursors which generate photoreactive species including dissolved organic matter (DOM), nitrate and bicarbonate were studied individually and in combination in the indirect photolysis batch experiments. Four surface water samples were collected from the metropolitan area in northern Taiwan and were used to study the effect of different water matrices. Results show that cyclophosphamide does not undergo direct photolysis while 5-fluorouracil can be directly photodegraded with initial concentration from 5 to 500 μg/L, having corresponding half-lives 45.5 ± 5.1 to 74.9 ± 17.8 hours. DOM, nitrate and bicarbonate demonstrated to be important factors for cyclophosphamide and 5-fluorouracil photodegradation. Produced by the three precursors, the hydroxyl radical (•OH) and singlet oxygen (1O2) can both react with cyclophosphamide and 5-fluorouracil, but triplet excited states of dissolved organic matter (3DOM*) and carbonate radical (•CO3-) can only react with 5-fluorouracil. Althought the matrices were quite complex in the four surface water samples, their overall photodegradation rate were consistent with the conclusion of the indirect photolysis batch experiments, it indicates that the selected three precursors are the major materials affecting the photodegradation in the aquatic environments.The half-lives of cyclophosphamide and 5-fluorouracil in JingMei River sample were 50.1 ± 0.5 and 9.2 ± 0.7 hours, indicating that cyclophosphamide is more persistent. This possibly explains its high occurrence in the nature aquatic environments.