QUANTITATION OF BISPHENOL A AND BISPHENOL A GLUCURONIDE IN BIOLOGICAL SAMPLES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

• Published in: Drug metabolism and disposition Vol. 33; no. 11; pp. 1748 - 1757
• Main Authors: Völkel, Wolfgang, Bittner, Nataly, Dekant, Wolfgang
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.11.2005; American Society for Pharmacology and Experimental Therapeutics
• Subjects: Benzhydryl Compounds; Biological and medical sciences; Chromatography, Gas; Chromatography, High Pressure Liquid; Estrogens, Non-Steroidal - blood; Estrogens, Non-Steroidal - pharmacokinetics; Estrogens, Non-Steroidal - urine; Female; Glucuronides - blood; Glucuronides - metabolism; Glucuronides - urine; Humans; Male; Medical sciences; Pharmacology. Drug treatments; Phenols - blood; Phenols - metabolism; Phenols - pharmacokinetics; Phenols - urine; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization - methods; Bisphenol A; Biological fluid; Mass spectrometry MS/MS; HPLC chromatography; Glucuroconjugate; Biological material; Quantitative analysis
• ISSN: 0090-9556; 1521-009X
• DOI: 10.1124/dmd.105.005454

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.