title: Development of a method for the determination of bisphenol A at trace concentrations in human blood and urine and elucidation of factors influencing method accuracy and sensitivity.
abstract: Bisphenol A (BPA) is an industrial chemical used to make polymers including some used in food contact applications. Virtually complete presystemic clearance of orally administered BPA occurs in humans by metabolism to BPA-glucuronide (BPA-G), but some biomonitoring studies report low concentrations of free (parent) BPA in human blood and urine. Trace contamination of BPA from exogenous sources or hydrolysis of BPA-G to free BPA, either during or after biomonitoring specimen collection, may have contributed to the reported concentrations of free BPA. An analytical method for the determination of free BPA in human blood and urine was developed and validated in two independent laboratories, using the latest generation of high-performance liquid chromatography-tandem mass spectrometry instrumentation to ensure the desired high sensitivity and selectivity. The method was designed to account for and/or eliminate background contamination from all sources and demonstrated that contamination could occur from devices used for specimen collection or storage, as well as other sources. The method employed an internal standard (BPA-d(8)) and demonstrated accuracy and reproducibility in both matrices fortified with BPA or a surrogate analyte ((13)C-BPA) at a low quantitation limit (0.1-0.2 ng/mL). For validation, five replicate samples were analyzed to evaluate reproducibility. Importantly, it was demonstrated that the conditions of the method did not result in the hydrolysis of BPA-G to free BPA, another possible source of error in BPA analysis. Application of the principles defined by this method will be critical to assure valid analytical results in any future biomonitoring studies.
authors.affiliation: The Dow Chemical Company, Toxicology and Environmental Research and Consulting, Midland, Michigan 48674, USA.
authors.forename: Dan Alan
authors.initials: DA
authors.lastname: Markham
authors.forename: John M
authors.initials: JM
authors.lastname: Waechter
authors.forename: Martina
authors.initials: M
authors.lastname: Wimber
authors.forename: Narayana
authors.initials: N
authors.lastname: Rao
authors.forename: Paul
authors.initials: P
authors.lastname: Connolly
authors.forename: Jane Chen
authors.initials: JC
authors.lastname: Chuang
authors.forename: Steven
authors.initials: S
authors.lastname: Hentges
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Shiotsuka
authors.forename: Stephen
authors.initials: S
authors.lastname: Dimond
authors.forename: Anne H
authors.initials: AH
authors.lastname: Chappelle
mesh_terms: D001559:Benzhydryl Compounds; D002851:Chromatography, High Pressure Liquid; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D010636:Phenols / Q000097:blood / Q000378:metabolism* / Q000652:urine; D053719:Tandem Mass Spectrometry; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds