title: Developing analytical approaches to explore the connection between endocrine-active pharmaceuticals in water to effects in fish.
abstract: The emphasis of this research project was to develop and optimize a solid-phase extraction method and high-performance liquid chromatography-electrospray ionization-mass spectrometry method, such that a linkage between the detection of endocrine-active pharmaceuticals (EAPs) in the aquatic environment and subsequent effects on fish populations could eventually be studied. Four EAPs were studied: tamoxifen (TAM), exemestane (EXE), letrozole (LET), anastrozole (ANA); and three TAM metabolites: 4-hydroxytamoxifen, e/z endoxifen, and n-desmethyl tamoxifen. In aqueous matrices, the use of isotopically labeled standards for the EAPs allowed for the generation of good recoveries, greater than 80 %, and low relative standard deviations (% RSDs) (3 to 27 %). TAM metabolites had lower recoveries in the spiked water matrices: 35 to 93 % in waste/source water compared to 58 to 110 % in DI water. The precision in DI water was acceptable ranging from 8 to 38 % RSD. However, the precision in real environmental wastewaters could be poor, ranging from 15 to 120 % RSD, dependent upon unique matrix effects. In plasma, the overall recoveries of the EAPs were acceptable: 88 to 110 %, with %RSDs of 6 to 18 % (Table 3). The spiked recoveries of the TAM metabolites from plasma were good, ranging from 77 to 120 %, with %RSDs ranging from 27 to 32 %. Two of the TAM metabolites, 4-hydroxytamoxifen and n-desmethyl tamoxifen, were confirmed in most of the environmental aqueous samples. The discovery of TAM metabolites demonstrates that the source of the TAM metabolites, TAM, is constant, introducing a pseudo-persistence of this chemical into the environment.
authors.affiliation: US Environmental Protection Agency, National Exposure Research Laboratory, Office of Research and Development, P.O. Box 93478, Las Vegas, NV, 89193, USA, jones-lepp.tammy@epa.gov.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Jones-Lepp
authors.forename: Randi L
authors.initials: RL
authors.lastname: Taniguchi-Fu
authors.forename: Jade
authors.initials: J
authors.lastname: Morgan
authors.forename: Trevor
authors.initials: T
authors.lastname: Nance
authors.forename: Matthew
authors.initials: M
authors.lastname: Ward
authors.forename: David A
authors.initials: DA
authors.lastname: Alvarez
authors.forename: Lesley
authors.initials: L
authors.lastname: Mills
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D052244:Endocrine Disruptors / Q000633:toxicity*; D005399:Fishes; D057230:Limit of Detection; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical