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Ready biodegradability of trifluoromethylated phenothiazine drugs, structural elucidation of their aquatic transformation products, and identification of environmental risks studied by LC-MSn and QSAR

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Abstract

The environmental fate of transformation products from organic pollutants such as drugs has become a new research area of increasing interest over the last few years. Whereas in the past mainly parent compounds or their major human metabolites were studied, new questions have arisen what compounds could be formed during incomplete degradation in the aquatic environment and what effects the resulting transformation products might have on nature and mankind. Psychiatric drugs are among the most important prescription drugs worldwide, but so far only little data is provided upon their degradation behavior. This especially accounts for tricyclic antipsychotic drugs of the phenothiazine class. Therefore, the degradation of such drugs was investigated in this study. In this study the aerobic Closed Bottle test (The Organisation for Economic Co-operation and Development (OECD) 301D) was used to assess the ready biodegradability of three trifluoromethylated phenothiazine drugs: fluphenazine, triflupromazine, and trifluoperazine. As it is known from literature that phenothiazine drugs can easily form various photolytic transformation products under light exposure, photochemical transformation was also investigated. Since transformation products are usually not available commercially, the calculation of environmental parameters with the aid of quantitative structure activity relationship (QSAR) software was used for first evaluation of these compounds. According to the OECD test guideline, all trifluoromethylated phenothiazines had to be classified as not readily biodegradable. Chromatographic data revealed the formation of some transformation products. Comparing retention time and mass spectrometric data with the analytical results of the light exposure experiments, we found peaks with the same retention time and mass spectra. So these transformation products were not of bacterial, but photolytic, origin and are formed very quickly even under low light doses. A special chromatographic column and solvent gradient along with multiple stage mass spectrometric fragmentation experiments uncovered the presence of, in total, nine photolytic transformation products and allowed for their structural elucidation. Typical modifications of the molecules were sulfoxidation, exocyclic N-oxidation, and transformation of the trifluoromethyl to a carboxylic moiety. The obtained results of the QSAR calculations show that all transformation products are highly mobile in the aquatic environment and elimination through biotic or abiotic pathways cannot be expected. Transformation products of trifluoromethylated phenothiazine drugs have to be expected in the aquatic environment, yet nothing is known about their toxicological properties. Therefore, further risk assessment upon these drugs and their fate is strongly recommended.

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Acknowledgments

The authors wish to thank Georg Fuchs (Institute for Biology II, Microbiology, University Freiburg) for fruitful discussions about bacterial metabolism of trifluoromethylated aromatic compounds. The authors wish to thank especially Christoph Lederer (Leuphana University Lüneburg) for calculation of QSAR parameters with the CASE Ultra software. This work was supported through Deutsche Bundesstiftung Umwelt (DBU) through a scholarship for Christoph Trautwein (grant no. 20007/940).

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  1. Department of Environmental Health Sciences, University Medical Centre Freiburg, Breisacher Str. 115B, 79106, Freiburg, Germany

    Christoph Trautwein

  2. Institute for Biology II, Microbiology, University Freiburg, Schänzlestrasse 1, 79104, Freiburg, Germany

    Christoph Trautwein

  3. Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststrasse 1, 21335, Lüneburg, Germany

    Christoph Trautwein & Klaus Kümmerer

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  1. Christoph Trautwein
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  2. Klaus Kümmerer
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Correspondence to Klaus Kümmerer.

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Trautwein, C., Kümmerer, K. Ready biodegradability of trifluoromethylated phenothiazine drugs, structural elucidation of their aquatic transformation products, and identification of environmental risks studied by LC-MSn and QSAR. Environ Sci Pollut Res 19, 3162–3177 (2012). https://doi.org/10.1007/s11356-012-1002-1

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