MSACL 2016 EU Abstract

Rapid and Sensitive Measurement of Bisphenol A and Bisphenol A Glucuronide in Serum and Urine Using UHPLC-MS/MS

Richard van Breemen (Presenter)
University of Illinois College of Pharmacy

Bio: Richard B. van Breemen is the Matthias C Lu Collegiate Professor of Pharmacy and Professor of Medicinal Chemistry and Pharmacognosy at the University of Illinois College of Pharmacy. He serves as Director of the UIC/NIH Center for Botanical Dietary Supplements Research and leads the Chicago Mass Spectrometry Laboratory, which he founded in 1994. Prof. van Breemen received his B.A. in chemistry from Oberlin College in 1980 and Ph.D. in Pharmacology and Experimental Therapeutics from the Johns Hopkins University in 1985. He carried out post-doctoral research in laser desorption mass spectrometry at Johns Hopkins before joining North Carolina State University in 1994 and then the University of Illinois College of Pharmacy. He is a Regional Editor of Biomedical Chromatography and on the editorial board of Assay and Drug Development Technologies.

Authorship: Richard B. van Breemen, Guannan Li and Zane Hauck
University of Illinois College of Pharmacy

Short Abstract

Used in plastics and thermal paper, bisphenol A (BPA) has received much attention due to its endocrine disruption potential and widespread human exposure. BPA can leach into food and beverages from BPA-containing containers, bottles or thermal paper and be consumed or absorbed through the skin. After absorption, BPA is rapidly metabolized to BPA glucuronide and to a small extent, BPA sulfate. Both conjugates are excreted in the urine. The measurement of BPA in biological samples is essential for risk assessment, but such analyses are challenging due to the trace levels of BPA in these samples and the possibility of background contamination. We developed methods based on UHPLC-MS/MS for the rapid quantitative analysis of both BPA and BPA-glucuronide in serum, urine and environmental samples.

Long Abstract

Introduction: Used in plastics and thermal paper, bisphenol A (BPA) has received much attention due to its endocrine disruption potential and widespread human exposure. BPA is found in thousands of consumer products including polycarbonate bottles, epoxy resins used to line the interior of food cans, thermal paper used for cash register receipts, and dental sealants. BPA has been shown to leach into food and beverages from BPA-containing containers and to be absorbed through the skin. In adults, BPA is rapidly metabolized to BPA glucuronide and to a small extent, BPA sulfate. Both conjugates are excreted in the urine. The measurement of BPA in biological samples is essential for risk assessment, but such analyses are challenging due to the trace levels of BPA in these samples and the possibility of background contamination.

Methods: Using a Shimadzu (Kyoto, Japan) 8060 UHPLC-MS/MS triple quadrupole mass spectrometer with collision-induced dissociation and selected reaction monitoring and Nexera UHPLC, we developed a quantitative method for the analysis of both BPA and intact BPA-glucuronide in serum and urine as well as drinking water.

Results: Unlike GC-MS/MS assays, our approach requires no derivatization of BPA, and unlike GC-MS/MS and some HPLC-MS/MS based assays, our method avoids hydrolysis of BPA-glucuronide. UHPLC was utilized instead of HPLC to shorten chromatographic separation time to less than 2 min per analysis. Sources of laboratory contamination by BPA could be eliminated to prevent interference. Most importantly, when volumes of serum samples are small, our method is unique in that only 25 µL of serum are required per analysis.

Conclusions: A fast and sensitive UHPLC-MS-MS method was developed for the quantitative analysis of BPA and its major metabolite BPA-glucuronide in serum and urine. BPA and BPA-glucuronide may be measured directly without hydrolysis to BPA and then derivatization. Compared with previous LC-MS/MS assays for BPA and BPA-glucuronide, the new UHPLC-MS/MS assay takes only 2 min and requires only 25 µL serum or urine. Simple sample preparation, fast analysis and small sample sizes will enable biological and environmental studies of the effects of BPA to be carried out more efficiently than was possible previously.


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