title: Bioconcentration and Biotransformation of Amitriptyline in Gilt-Head Bream.
abstract: Extensive global use of the serotonin-norepinephrine reuptake inhibitor Amitriptyline (AMI) for treatment of mental health problems has led to its common occurrence in the aquatic environment. To assess AMI bioconcentration factors, tissue distribution, and metabolite formation in fish, we exposed gilt-head bream (Sparus aurata) to AMI in seawater for 7 days at two concentrations (0.2 μg/L and 10 μg/L). Day 7 proportional bioconcentration factors (BCFs) ranged from 6 (10 μg/L dose, muscle) to 127 (0.2 μg/L dose, brain) and were consistently larger at the low dose level. The relative tissue distribution of AMI was consistent at both doses, with concentrations decreasing in the order brain ≈ gill > liver > plasma > bile ≫ muscle. Using a suspect screening workflow based on liquid chromatography-high resolution (Orbitrap) mass spectrometry we identified 33 AMI metabolites (both Phase I and Phase II), occurring mostly in bile, liver and plasma. Ten structures are reported for the first time. Remarkably, all 33 metabolites retained the tricyclic ring structure common to tricyclic antidepressants, which may be toxicologically relevant. Collectively these data indicate that, in addition to AMI, a broad suite of metabolites should be included in biomonitoring campaigns in order to fully characterize exposure in aquatic wildlife.
authors.affiliation: Department of Analytical Chemistry, University of the Basque Country (UPV/EHU) , Leioa, Basque Country, Spain.|Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University , Stockholm, Sweden.
authors.forename: Haizea
authors.identifier: 0000-0002-8951-0466
authors.initials: H
authors.lastname: Ziarrusta
authors.affiliation: Department of Analytical Chemistry, University of the Basque Country (UPV/EHU) , Leioa, Basque Country, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Mijangos
authors.affiliation: Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU) , Plentzia, Basque Country, Spain.
authors.forename: Urtzi
authors.initials: U
authors.lastname: Izagirre
authors.affiliation: Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University , Stockholm, Sweden.
authors.forename: Merle M
authors.initials: MM
authors.lastname: Plassmann
authors.affiliation: Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University , Stockholm, Sweden.
authors.forename: Jonathan P
authors.identifier: 0000-0001-5940-637X
authors.initials: JP
authors.lastname: Benskin
authors.affiliation: Department of Organic Chemistry, University of the Basque Country (UPV/EHU) , Leioa, Basque Country, Spain.
authors.forename: Eneritz
authors.initials: E
authors.lastname: Anakabe
authors.affiliation: Department of Analytical Chemistry, University of the Basque Country (UPV/EHU) , Leioa, Basque Country, Spain.
authors.forename: Maitane
authors.initials: M
authors.lastname: Olivares
authors.affiliation: Department of Analytical Chemistry, University of the Basque Country (UPV/EHU) , Leioa, Basque Country, Spain.|Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU) , Plentzia, Basque Country, Spain.
authors.forename: Olatz
authors.initials: O
authors.lastname: Zuloaga
mesh_terms: D000639:Amitriptyline; D000818:Animals; D001711:Biotransformation; D005260:Female; D005880:Gills / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D021541:Sea Bream / Q000378:metabolism; D013552:Swine; D014874:Water Pollutants, Chemical
chemical_list: D014874:Water Pollutants, Chemical; D000639:Amitriptyline