Catalan Institute for Water Research (ICRA), Carrer Emili Grahit 101, 17003 Girona, Spain.
Universitat de Girona, Girona, Spain.
Environ Sci Technol. 2020 Jul 21;54(14):9062-9073. doi: 10.1021/acs.est.0c00944. Epub 2020 Jul 9.
Antibiotic transformation products (TPs) generated during water treatment can be considered as an environmental concern, since they can retain part of the bioactivity of the parent compound. Effect-directed analysis (EDA) was applied for the identification of bioactive intermediates of azithromycin (AZI) and ciprofloxacin (CFC) after water chlorination. Fractionation of samples allowed the identification of bioactive intermediates by measuring the antibiotic activity and acute toxicity, combined with an automated suspect screening approach for chemical analysis. While the removal of AZI was in line with the decrease of bioactivity in chlorinated samples, an increase of bioactivity after complete removal of CFC was observed (at >0.5 mgCl/L). Principal component analysis (PCA) revealed that some of the CFC intermediates could contribute to the overall toxicity of the chlorinated samples. Fractionation of bioactive samples identified that the chlorinated TP296 (generated from the destruction of the CFC piperazine ring) maintained 41%, 44%, and 30% of the antibiotic activity of the parent compound in chlorinated samples at 2.0, 3.0, and 4.0 mgCl/L, respectively. These results indicate the spectrum of antibacterial activity can be altered by controlling the chemical substituents and configuration of the CFC structure with chlorine. On the other hand, the potential presence of volatile DBPs and fractionation losses do not allow for tentative confirmation of the main intermediates contributing to the acute toxic effects measured in chlorinated samples. Our results encourage further development of new and advanced methodologies to study the bioactivity of isolated unknown TPs to understand their hazardous effects in treated effluents.
抗生素在水处理过程中产生的转化产物（TPs）可能被视为环境关注点，因为它们可以保留母体化合物的部分生物活性。本文采用效应导向分析（EDA）鉴定了氯消毒后阿奇霉素（AZI）和环丙沙星（CFC）的生物活性中间体。通过测量抗生素活性和急性毒性，并结合化学分析的自动可疑物筛选方法，对样品进行分级，从而鉴定生物活性中间体。尽管 AZI 的去除与氯消毒样品中生物活性的降低一致，但在完全去除 CFC 后观察到生物活性增加（>0.5 mgCl/L）。主成分分析（PCA）表明，CFC 中间体的一些可以对氯消毒样品的整体毒性产生贡献。对生物活性样品的分级表明，氯代产物 TP296（由 CFC 哌嗪环破坏产生）在 2.0、3.0 和 4.0 mgCl/L 的氯消毒样品中分别保留了母体化合物抗生素活性的 41%、44%和 30%。这些结果表明，通过控制母体化合物的化学取代基和 CFC 结构的构型，用氯可以改变其抗菌活性谱。另一方面，挥发性 DBP 的潜在存在和分级损失不允许对测量的氯消毒样品中急性毒性效应的主要中间体进行暂定确认。我们的研究结果鼓励进一步开发新的和先进的方法来研究分离的未知 TPs 的生物活性，以了解它们在处理废水中的有害影响。
