Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry
Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry
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DOI：
10.1038/jes.2017.28
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发表时间：
2018-03-01
影响因子：
4.5
通讯作者：
Woodruff, Tracey J.
中科院分区：
文献类型：
--
作者：
Gerona, Roy R.;Schwartz, Jackie M.;Woodruff, Tracey J.
高分辨率质谱（MS）作为环境化学监测的发现工具的使用和优势已被证明是环境样品，但不是生物样品。我们开发了一种方法，使用液相色谱-四极杆飞行时间质谱（LC-QTOF/MS）发现以前未测量的环境化学物质在人血清中。使用非靶向数据采集（全扫描MS分析），我们能够筛选环境中的有机酸（EOAs）在20个血清样本中从中期妊娠妇女。我们将EOA定义为具有至少一个可解离质子的环境有机化合物，其用于商业用途。EOA包括环境酚类、邻苯二甲酸酯代谢物、全氟化合物、多溴二苯醚和多氯联苯的酚类代谢物以及酸性农药和/或预测的酸性农药代谢物。我们验证的方法使用固相萃取，反相色谱在C18柱梯度洗脱，电喷雾离子化在负极性和自动串联MS（MS/MS）数据采集，以最大限度地提高真阳性率。我们使用Agilent MassHunter定性分析软件识别“可疑EOA”，以将每个样品运行生成的化学式与我们从多个环境文献来源收集的693个EOA的独特数据库中的分子式进行匹配。我们在数据库中发现了282个（41%）EOA的潜在匹配。在至少75%的样本中检测到65种可疑EOA;目前只有19种化合物在国家健康和营养检查调查中进行生物监测。我们使用通过LC-MS/MS开发的靶向方法，通过LC-QTOF/MS确认了三种可疑EOA中的两种，报告了孕妇血清中二苯甲酮-1和双酚S的首次确认。我们的可疑筛选工作流程提供了一种全面扫描人类环境化学品暴露的方法。这可以提供更好的暴露信息来源，以帮助改善工业化学品的暴露和风险评估。
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.