Faculty of Science, University of South Bohemia, Branišovská 1716/31c, 370 05, České Budějovice, Czech Republic.
Faculty of AgriSciences, Department of Zoology, Fisheries, Hydrobiology and Apiculture, Mendel University in Brno, Zemědělská 1, 613 00, Brno, Czech Republic.
Environ Sci Pollut Res Int. 2020 Oct;27(28):35650-35660. doi: 10.1007/s11356-020-09830-w. Epub 2020 Jun 29.
Pathways of photochemical degradation of a cardiovascular drug verapamil under conditions relevant to natural waters and the toxicity of the photoproducts to Daphnia magna were investigated. Photodegradation was shown to proceed via photocatalysed mechanism. Two main photodegradation pathways were recognised: the first leading to hydroxylation at the methylamino position followed by splitting of verapamil molecule into two fragments, and the second providing the main active metabolite of verapamil, norverapamil, and a series of norverapamil isomers, followed again by their splitting at the amino group position. Twenty-two products of photodegradation were identified. Toxicity assays in sublethal concentrations of the parental drug, of the photoproduct mixture, and of norverapamil revealed no direct negative response in Daphnia magna to verapamil. On the other hand, photochemical products significantly lowered the number of juveniles, number of clutches, and body size of Daphnia. The exposition of Daphnia to norverapamil showed the same but even more pronounced effects than its exposition to the mixture of photoproducts, which leads to the conclusion that norverapamil is mainly responsible for the toxicity of photoproduct mixture and represents a noteworthy threat to aquatic invertebrates.
研究了心血管药物维拉帕米在与天然水相关的条件下的光化学降解途径，以及光产物对大型蚤的毒性。光降解被证明是通过光催化机制进行的。识别出两种主要的光降解途径：第一条途径导致甲基氨基位置的羟化，随后维拉帕米分子分裂成两个片段，第二条途径提供维拉帕米的主要活性代谢物去甲维拉帕米和一系列去甲维拉帕米异构体，然后再次在氨基位置分裂。鉴定出光降解的 22 种产物。在亚致死浓度下对母体药物、光产物混合物和去甲维拉帕米进行的毒性测定显示，大型蚤对维拉帕米没有直接的负面反应。另一方面，光化学产物显著降低了大型蚤的幼体数量、卵囊数量和身体大小。与暴露于光产物混合物相比，暴露于去甲维拉帕米的大型蚤表现出相同但更明显的效果，这得出结论，去甲维拉帕米是光产物混合物毒性的主要原因，对水生无脊椎动物构成显著威胁。
