Abstract
Bisphenol A (BPA) is a weak estrogen. Pharmacokinetic studies of BPA have demonstrated a rapid and extensive metabolism of BPA to the nonestrogenic BPA-monoglucuronide (BPA-gluc). Some investigators have reported that BPA was found at parts per billion concentrations in the tissues or urine of humans without known exposure to BPA. This work developed a rapid and sensitive method for the determination of BPA and BPA-gluc in plasma and urine based on liquid chromatography-tandem mass spectrometry. The liquid chromatography-electrospray ionization-tandem mass spectrometry method for quantitation of BPA and BPA-gluc uses stable isotope-labeled internal standards. A linear ion trap mass spectrometer permits identification and quantitation of BPA-gluc and BPA without sample workup. Development of separation conditions reduced the BPA-background in solvent samples to below 2.5 pmol/ml for BPA. Limit of quantitation (LOQ) for BPA in control urine was 15 pmol/ml; LOQ for BPA-gluc was 65 pmol/ml. Application of the method to urine samples from human subjects (n = 6) after administration of 25 μg of BPA/person (estimated maximum human daily intake) permitted the determination of excretion kinetics for BPA-gluc; BPA was below the LOD in all except two of the samples. In urine or blood samples of human subjects (n = 19) without intentional exposure to BPA, BPA concentrations were always below the limit of detection (≈2.5 pmol/ml) with or without prior glucuronidase treatment. The results show that care is required for analysis of BPA and its major metabolite BPA-gluc. The LOD obtained and the absence of detectable levels of BPA in samples from individuals suggests that general exposure of humans to BPA is much lower than the worst-case exposure scenario developed.
Footnotes
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This work was supported in part by the German Umweltbundesamt (F1E-Vorhabenkennzeichen 297 61 001/06). Mass spectrometry equipment was purchased by grants supported by the Deutsche Forschungsgemeinschaft and the State of Bavaria. The authors declare no competing interest.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.005454.
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ABBREVIATIONS: BPA, bisphenol A; BPA-gluc, BPA-monoglucuronide; DP, declustering potential; EPI, enhanced product ion; ER, enhanced resolution; IDA, information-dependent acquisition; LOD, limit of detection; LOQ, limit of quantitation; MRM, multiple reaction monitoring; S/N, signal to noise ratio; GC-MS, gas chromatography-mass spectrometry; LC-MS/MS, liquid chromatography-tandem mass spectrometry; HPLC, high-performance liquid chromatography; amu, atomic mass unit(s).
- Received May 9, 2005.
- Accepted August 15, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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