RATIONALE: The environmental fate of the organic pollutants such as drugs and their transformation products has received an increasing interest as a new research area over the last years. Psychiatric drugs are among the most important prescription drugs worldwide, therefore environmental fate and persistence of these pharmaceuticals and their degradation products is of high relevance and it is, yet, scarcely elucidated. Chlorprothixene (CPTX) is an antipsychotic drug of the thioxanthene class.
METHODS: The photodegradation of CPTX was conducted using 150 W medium-pressures Hg-lamp and Xenon lamp in Ultra-pure water. The elimination process was continuously monitored to follow the transformation and mineralization rate of the parent compound using Liquid Chromatography combined with UV-Vis detection (LC–UV-Vis) and total organic carbon (TOC), respectively. Liquid chromatography coupled to ion-trap mass spectrometry (ESI–LC–MS/MS (ion-trap)) was employed to monitor and identify the newly formed photo-transformation products (PTPs). Biodegradation testing of CPTX itself and samples from photolysis was assessed employing standardized OECD tests: Closed Bottle test (CBT; OECD 301 D) and Manometric Respirometry test (MRT; OECD 301 F). Environmentally relevant properties and selected toxicity endpoints of CPTX and its PTPs were predicted using different QSAR software: Oasis Catalogic software V.5.11.6 TB, Case Ultra V 1.4.5.1, OECD QSAR toolbox V 3.2 and Leadscope software V.3.0.11-1.
RESULTS: It was found that CPTX underwent complete transformation after 64 min with 13% mineralization under UV irradiation. The mineralization reached 33% after 128 min irradiation time. In case of xenon lamp, CPTX was partially transformed to its geometric isomer without any mineralization. Moreover, according to mass data, the putative molecular formulae for twenty different PTPs for CPTX could be established, most of them unprecedented. Thus, a pathway for the photo-transformation of CPTX in aqueous medium could be proposed. Neither the CPTX nor its PTPs were biodegradable in the OECD tests. There was a good correlation between the experimental findings for the PTPs and the modelled environmental relevant properties from the QSAR applications. Finally, in silico toxicity analysis of CPTX and its PTPs provided evidence for carcinogenicity, ecotoxicity and mutagenicity.
CONCLUSIONS: These results indicate the importance of identification of the PTPs arising from photolysis treatment as these PTPs can be more hazardous to the environment than their parent compounds.