title: Degradation of the anticancer drug erlotinib during water chlorination: Non-targeted approach for the identiﬁcation of transformation products.
abstract: Erlotinib is a highly potent tyrosine kinase inhibitor used in the treatment of the most common type of lung cancer. Due to its recent introduction, very scarce information is available on its occurrence, environmental fate and toxicological effects on aquatic organisms. During chlorination processes normally carried out in wastewater treatment plants and in the pretreatment of hospital effluents, chlorinated transformation products can be formed with an enhanced toxicity relative to the parent compound. Thus, the reactivity of the cytostatic drug erlotinib in free chlorine-containing water was investigated for the first time in the present work. A non-targeted screening approach based on the use of differential profiling tools was applied in order to reveal its potential transformation products. Structural elucidation of the detected transformation products was performed by ultra-performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. The proposed approach allowed detecting a total of nineteen transformation products, being eighteen of them described for the first time in this work, which demonstrates its potential in environmental analysis. Among them, six compounds presented chlorine atoms in their structures, which may be of major concern. Other transformation products involved hydroxylation and oxidation reactions. Time-course profiles of erlotinib and its transformation products were followed in real wastewater samples under conditions that simulate wastewater disinfection. Although the structures of these transformation products could not be positively confirmed due to lack of standards, their chemical formulas and product ions can be added to databases, which will allow their screening in future monitoring studies.
authors: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, E-08034, Barcelona, Spain.
authors: Noelia
authors: N
authors: Negreira
authors: Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, Ourense Campus, University of Vigo, E-32004, Ourense, Spain.
authors: Jorge
authors: J
authors: Regueiro
authors: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, E-08034, Barcelona, Spain. Electronic address: mlaqam@cid.csic.es.
authors: Miren
authors: M
authors: López de Alda
authors: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, E-08034, Barcelona, Spain; Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, Emili Grahit 101, E-17003, Girona, Spain.
authors: Damià
authors: D
authors: Barceló
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D004202:Disinfectants / Q000737:chemistry; D000069347:Erlotinib Hydrochloride / Q000032:analysis / Q000737:chemistry*; D054879:Halogenation; D053719:Tandem Mass Spectrometry; D014865:Waste Disposal, Fluid / Q000379:methods; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004202:Disinfectants; D014874:Water Pollutants, Chemical; D002713:Chlorine; D000069347:Erlotinib Hydrochloride
keywords: Cytostatic drugs; Degradation; Free chlorine; Orbitrap; Reactivity; Untargeted