The use and advantages of high-resolution mass spectrometry (MS) as a discovery tool for environmental chemical monitoring has been demonstrated for environmental samples but not for biological samples. We developed a method using liquid chromatography–quadrupole time-of-flight MS (LC–QTOF/MS) for discovery of previously unmeasured environmental chemicals in human serum. Using non-targeted data acquisition (full scan MS analysis) we were able to screen for environmental organic acids (EOAs) in 20 serum samples from second trimester pregnant women. We define EOAs as environmental organic compounds with at least one dissociable proton which are utilized in commerce. EOAs include environmental phenols, phthalate metabolites, perfluorinated compounds, phenolic metabolites of polybrominated diphenyl ethers and polychlorinated biphenyls, and acidic pesticides and/or predicted acidic pesticide metabolites. Our validated method used solid phase extraction, reversed-phase chromatography in a C18 column with gradient elution, electrospray ionization in negative polarity and automated tandem MS (MS/MS) data acquisition to maximize true positive rates. We identified “suspect EOAs” using Agilent MassHunter Qualitative Analysis software, to match chemical formulas generated from each sample run with molecular formulas in our unique database of 693 EOAs assembled from multiple environmental literature sources. We found potential matches for 282 (41%) of the EOAs in our database. Sixty-five of these suspect EOAs were detected in at least 75% of the samples; only 19 of these compounds are currently biomonitored in National Health and Nutrition Examination Survey. We confirmed two of three suspect EOAs by LC–QTOF/MS using a targeted method developed through LC–MS/MS, reporting the first confirmation of benzophenone-1 and bisphenol S in pregnant women’s sera. Our suspect screening workflow provides an approach to comprehensively scan environmental chemical exposures in humans. This can provide a better source of exposure information to help improve exposure and risk evaluation of industrial chemicals.
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We thank the staff and faculty at San Francisco General Hospital Women’s Options Center for their assistance in blood sample collection. We also thank Katie Stevenson, Dylan Atchley, Mei-Lani Bixby and Cynthia Megloza for their assistance in recruitment and data collection, and Shorey Myers and Clayton Bloszies for their assistance in putting together the EOA database. This project was supported by NIH grants P20 ES018135, R21 ES017763, R01 ES013527, R01HD31544, R01 ES027051, P01 ES022841 (funded jointly by NIEHS and the US Environmental Protection Agency), EPA RD-83543301, EPA RD-83564301, California EPA P0050869 and the Passport Foundation.
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website
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Gerona, R., Schwartz, J., Pan, J. et al. Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography–quadrupole time-of-flight mass spectrometry. J Expo Sci Environ Epidemiol 28, 101–108 (2018). https://doi.org/10.1038/jes.2017.28
- endocrine disruptors
- environmental organic acids
- liquid chromatography-quadrupole time-of-flight mass spectrometry
- non-targeted analysis, suspect screening
Gaussian graphical modeling of the serum exposome and metabolome reveals interactions between environmental chemicals and endogenous metabolites
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