Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Pathogen Biology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, Jiangsu, China.
Chemosphere. 2020 Dec;260:127579. doi: 10.1016/j.chemosphere.2020.127579. Epub 2020 Jul 11.
As important emerging contaminants, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most intensively prescribed pharmaceuticals introduced to drinking water due to their incomplete removal in wastewater treatment. While concentrations of NSAIDs in drinking water are generally low, they have been attracting increasing concern as a result of their disinfection byproducts (DBPs) generated in drinking water disinfection. In this work, detection methods were set up for four representative indole-derivative NSAIDs (indomethacin, acemetacin, sulindac, and etodolac) using ultra performance liquid chromatography/electrospray ionization-triple quadruple mass spectrometry (UPLC/ESI-tqMS). ESI+ was better for detection of indomethacin and sulindac, whereas ESI- was suitable to detection of acemetacin and etodolac. With optimized MS parameters, the instrument detection and quantitation limits of the four indole derivatives were achieved to be 1.1-24.6 ng/L and 3.7-41.0 ng/L, respectively. During chlorination, indomethacin and acemetacin could undergo five major reaction types (chlorine substitution, hydrolysis, decarboxylation, C-C coupling, and C-N cleavage) to form a series of DBPs, among which 19 were proposed/identified with structures. Based on the revealed structures of DBPs, transformation pathways of indomethacin and acemetacin in chlorination were partially elucidated. Notably, individual and mixture toxicity of indomethacin and acemetacin before/after chlorination were evaluated using a well-established acute toxicity assessment and a Hep G2 cell cytotoxicity assay, respectively. Results showed that the predicted acute toxicity of a few chlorination DBPs were higher than their precursors; chlorination substantially enhanced the mixture cytotoxicity of indomethacin by over 10 times and slightly increased the mixture cytotoxicity of acemetacin.
作为重要的新兴污染物，非甾体抗炎药（NSAIDs）由于在废水处理中未被完全去除，是引入饮用水中被最广泛使用的药物。尽管饮用水中 NSAIDs 的浓度通常较低，但由于其在饮用水消毒过程中产生的消毒副产物（DBPs），已引起越来越多的关注。在这项工作中，使用超高效液相色谱/电喷雾电离-三重四极杆质谱法（UPLC/ESI-tqMS）建立了四种代表性吲哚衍生物 NSAIDs（吲哚美辛、乙酰水杨酸、舒林酸和依托度酸）的检测方法。ESI+ 更适合检测吲哚美辛和舒林酸，而 ESI- 更适合检测乙酰水杨酸和依托度酸。通过优化 MS 参数，四种吲哚衍生物的仪器检测限和定量限分别达到 1.1-24.6 ng/L 和 3.7-41.0 ng/L。在氯化过程中，吲哚美辛和乙酰水杨酸可经历五种主要的反应类型（氯取代、水解、脱羧、C-C 偶联和 C-N 裂解），形成一系列 DBPs，其中 19 个被提出/鉴定具有结构。基于揭示的 DBPs 结构，部分阐明了氯化过程中吲哚美辛和乙酰水杨酸的转化途径。值得注意的是，使用成熟的急性毒性评估和 Hep G2 细胞细胞毒性测定分别评估了氯化前后吲哚美辛和乙酰水杨酸的单独和混合物毒性。结果表明，一些氯化 DBPs 的预测急性毒性高于其前体；氯化显著增加了吲哚美辛混合物的细胞毒性超过 10 倍，略微增加了乙酰水杨酸混合物的细胞毒性。
