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Development of a UPLC-MS/MS method for the determination of ten anticancer drugs in hospital and urban wastewaters, and its application for the screening of human metabolites assisted by information-dependent acquisition tool (IDA) in sewage samples

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Abstract

In the present work, the development, optimization, and validation (including a whole stability study) of a fast, reliable, and comprehensive method for the analysis of ten anticancer drugs in hospital and urban wastewater is described. Extraction of these pharmaceutical compounds was performed using automated off-line solid-phase extraction followed by their determination by ultra-performance liquid chromatography coupled to a triple quadrupole–linear ion trap mass spectrometer. Target compounds include nine cytotoxic agents: cyclophosphamide, ifosfamide, docetaxel, paclitaxel, etoposide, vincristine, tamoxifen, methotrexate, and azathioprine; and the cytotoxic quinolone, ciprofloxacin. Method detection limits (MDL) ranged from 0.8 to 24 ng/L. Levels found of cytostatic agents in the hospital and wastewater influents did not differ significantly, and therefore, hospitals cannot be considered as the primary source of this type of contaminants. All the target compounds were detected in at least one of the influent samples analyzed: Ciprofloxacin, cyclophosphamide, tamoxifen, and azathioprine were found in most of them and achieving maximum levels of 14.725, 0.201, 0.133, and 0.188 μg/L, respectively. The rest of target cancer drugs were less frequently detected and at values ranging between MDL and 0.406 μg/L. Furthermore, a feasible, useful, and advantageous approach based on information acquisition tool (information-dependent acquisition) was used for the screening of human metabolites in hospital effluents, where the hydroxy tamoxifen, endoxifen, and carboxyphosphamide were detected.

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Acknowledgments

This study has been co-financed by the Spanish Ministry of Economy and Competitiveness, and the European Union through the European Regional Development Fund (FEDER), through the national research projects (CTQ2010-21776-C02-02, DEGRAPHARMAC), the European projects (FP7-ENV-2011-ECO-INNOVATION, ENDETECH), and The Catalan Agency for Administration of University and Research Grants (AGAUR, 2009 CTP 00034, MBRMed). This work was partly supported by the Generalitat de Catalunya (Consolidated Research Group: Water and Soil Quality Unit 2009-SGR-965). The authors would further like to thank the Consorci de la Costa Brava, the members of Castell d`Aro WWTP, TRARGISA S.A. (Tractament de Residus i d'Aigües Residuals del Sistema de Girona), and Jose Vicente Bon in charge of Green Office from CHGUV (Consorcio Hospital General Universitario de Valencia). Prof. Barceló acknowledges King Saud University for his visiting professorship.

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Authors and Affiliations

  1. ICRA, Catalan Institute for Water Research, Carrer Emili Grahit, 101, Parc Científic i Tecnològic de la Universitat de Girona, 17003, Girona, Spain

    L. Ferrando-Climent, S. Rodriguez-Mozaz & D. Barceló

  2. Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), CSIC, c/Jordi Girona 18-26, 08034, Barcelona, Spain

    D. Barceló

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  1. L. Ferrando-Climent
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  2. S. Rodriguez-Mozaz
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Correspondence to S. Rodriguez-Mozaz.

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Published in the special paper collection Liquid Chromatography–Tandem Mass Spectrometry with guest editors Damià Barceló and Mira Petrovic.

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Ferrando-Climent, L., Rodriguez-Mozaz, S. & Barceló, D. Development of a UPLC-MS/MS method for the determination of ten anticancer drugs in hospital and urban wastewaters, and its application for the screening of human metabolites assisted by information-dependent acquisition tool (IDA) in sewage samples. Anal Bioanal Chem 405, 5937–5952 (2013). https://doi.org/10.1007/s00216-013-6794-4

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