Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Universitätsallee 1 C13, DE-21335, Lüneburg, Germany; Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt.
Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Universitätsallee 1 C13, DE-21335, Lüneburg, Germany.
Water Res. 2019 Feb 1;149:467-476. doi: 10.1016/j.watres.2018.10.075. Epub 2018 Nov 8.
Chlorprothixene (CPTX) is an antipsychotic drug of the thioxanthene class. Although it is widely used as a tranquillizer in psychiatry, anesthesiology, pediatrics, and in general medical practice, there is a gap in knowledge regarding its occurrence and fate in the environment. Therefore, we provide for the first-time data on the environmental fate and ecotoxicity of CPTX and its potential photo-transformations products (PTPs). Firstly, two standardized biodegradation tests (Closed Bottle test (CBT) and Manometric Respiratory test (MRT)) were performed to assess CPTX's environmental biodegradability. Then, its photodegradability was studied using Xenon and UV lamps. Effects of different conditions (initial drug concentration, pH, and temperature) were applied during UV-photodegradation. Subsequently, the time courses of CPTX and dissolved organic carbon (DOC) concentrations were monitored throughout the photodegradation tests. After that, high-resolution mass spectrometry was employed to elucidate the structures of the formed photo-transformation products (PTPs). In addition, biodegradation tests were performed for the photolytic mixtures to assess the biodegradability of the PTPs. Finally, the (eco)toxicity assessment for CPTX and its photolytic mixtures was predicted using different (quantitative) structure-activity relationship ((Q)SAR) software. CPTX was found to be not readily biodegradable in CBT and MRT. CPTX was not eliminated by irradiation with the Xenon lamp, however primarily eliminated using the UV-lamp. The CPTX elimination during UV-irradiation was faster at lower concentrations. CPTX UV-photodegradation was affected by pH value, while not affected by the temperature of the irradiated solution. 13 PTPs were detected in UV-photolysis mixtures. One additional product was detected in CPTX standard solution, and it was degraded simultaneously with CPTX during UV-irradiation. On one hand, Biodegradation assays revealed that UV-photolytic mixtures of CPTX, containing its PTPs, were not better biodegradable than CPTX itself. On the other hand, LC-MS analysis showed some PTPs which were eliminated after the biodegradation tests indicating possible biodegradability of these PTPs. This because those PTPs are present in low concentrations in the photolysis mixture and their effect can be hindered by the effect of CPTX and other non-biodegradable PTPs. QSAR analysis revealed that CPTX and some of its PTPs may have some human and/or eco-toxic properties. In conclusion, the release of CPTX into aquatic environments could be harmful. Therefore, further research focusing on CPTX and its PTPs are strongly recommended.
氯普噻吨（CPTX）是噻吨类抗精神病药物。尽管它在精神病学、麻醉学、儿科学和一般医学实践中被广泛用作镇静剂，但关于其在环境中的存在和命运的知识仍存在空白。因此，我们首次提供了关于 CPTX 及其潜在光转化产物（PTP）的环境归趋和生态毒性的数据。首先，进行了两项标准化生物降解测试（密闭瓶测试（CBT）和呼吸计呼吸测试（MRT）），以评估 CPTX 的环境生物降解性。然后，使用氙气和紫外线灯研究了其光降解性。在 UV 光降解过程中应用了不同的条件（初始药物浓度、pH 值和温度）。随后，在整个光降解测试过程中监测 CPTX 和溶解有机碳（DOC）浓度的时间过程。之后，采用高分辨率质谱法阐明了形成的光转化产物（PTPs）的结构。此外，对光解混合物进行了生物降解测试，以评估 PTPs 的生物降解性。最后，使用不同的（定量）构效关系（QSAR）软件对 CPTX 及其光解混合物的（生态）毒性进行了预测。结果表明，CPTX 在 CBT 和 MRT 中不易生物降解。CPTX 用氙气灯照射不会被消除，但是用紫外线灯主要被消除。在较低浓度下，CPTX 在 UV 照射下的消除速度更快。CPTX 的 UV 光降解受 pH 值影响，而不受辐照溶液温度影响。在 UV 光解混合物中检测到 13 种 PTPs。在 CPTX 标准溶液中检测到一种额外的产物，它在 UV 辐照下与 CPTX 同时降解。一方面，生物降解试验表明，CPTX 的光解混合物及其 PTPs 的生物降解性并不优于 CPTX 本身。另一方面，LC-MS 分析表明，一些 PTPs 在生物降解试验后被消除，表明这些 PTPs 可能具有生物降解性。这是因为这些 PTPs 在光解混合物中的浓度较低，其作用可能会受到 CPTX 和其他不可生物降解的 PTPs 的影响。QSAR 分析表明，CPTX 和其一些 PTPs 可能具有一定的人类和/或生态毒性。总之，CPTX 释放到水生环境中可能是有害的。因此，强烈建议进一步研究 CPTX 及其 PTPs。
