title: Transformation of tamoxifen and its major metabolites during water chlorination: Identification and in silico toxicity assessment of their disinfection byproducts.
abstract: The selective estrogen receptor modulator tamoxifen is the most commonly used drug for the treatment and prevention of breast cancer. Tamoxifen is considered as a pro-drug since it is known to exert its pharmacological effect through its major active metabolites, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen, which are mainly excreted in the urine in the days following administration. In the present work, the reactivity of tamoxifen and its major active metabolites in free chlorine-containing water was investigated for the first time. Under the studied chlorination conditions, tamoxifen was fairly stable whereas its metabolites were quickly degraded. A total of thirteen chlorinated byproducts were tentatively identified by ultra-high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. Time-course profiles of the identified byproducts were followed in real wastewater samples under conditions that simulate wastewater disinfection. A preliminary assessment of their acute aquatic toxicity at two trophic levels by means of quantitative structure-activity relationship models showed that the identified byproducts were up to 110-fold more toxic than the parent compounds.
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: D002851:Chromatography, High Pressure Liquid; D004203:Disinfection; D054879:Halogenation; D021281:Quantitative Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D018508:Water Purification
chemical_list: D014874:Water Pollutants, Chemical; D013629:Tamoxifen; C016601:afimoxifene; C055492:4-hydroxy-N-desmethyltamoxifen
keywords: Chlorine; Cytostatic drugs; Orbitrap; Reactivity; Tamoxifen; Transformation products