title: Quantification of deuterated bisphenol A in serum, tissues, and excreta from adult Sprague-Dawley rats using liquid chromatography with tandem mass spectrometry.
abstract: Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products, epoxy resin-based food can liners, and paper products. The presence of BPA in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure and is problematic because of the potential for endocrine disruption. The ubiquity of environmental BPA in common laboratory supplies used for sample collection, storage, and analysis greatly increases the likelihood of false positive determinations, particularly at trace levels. The current study validated using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in conjunction with deuterated BPA as the dosing material to circumvent contamination for high sensitivity quantifications in rat serum, tissues, urine, and feces. The methods described provided measurements of both estrogen receptor-active aglycone and metabolically deactivated conjugated forms of BPA, a distinction that is critical to assessing toxicological potential. The adequacy of the described methodology was substantiated by its utility in analyzing samples from rats treated orally with a 100 µg/kg body weight dose of d6-BPA. These results emphasize the challenges inherent in measuring BPA in biological samples and how employing stable isotope labeled dosing can facilitate pharmacokinetic studies needed to understand BPA metabolism and disposition. Such studies conducted in experimental animal models, in conjunction with properly validated human biomonitoring data, will be the basis for PBPK modeling of BPA in environmentally exposed humans.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Twaddle
authors.forename: Mona I
authors.initials: MI
authors.lastname: Churchwell
authors.forename: Michelle
authors.initials: M
authors.lastname: Vanlandingham
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D002853:Chromatography, Liquid / Q000379:methods*; D019411:Clinical Laboratory Techniques / Q000592:standards; D003903:Deuterium / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000652:urine; D005243:Feces / Q000737:chemistry*; D005260:Female; D010636:Phenols / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003903:Deuterium; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds