Clinical Toxicology and Environmental Biomonitoring Laboratory, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
J Expo Sci Environ Epidemiol. 2018 Mar;28(2):101-108. doi: 10.1038/jes.2017.28. Epub 2017 Oct 11.
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.
高分辨率质谱（MS）作为环境化学监测的发现工具的用途和优势已在环境样品中得到证明，但尚未在生物样品中得到证明。我们开发了一种使用液相色谱-四极杆飞行时间质谱（LC-QTOF/MS）的方法，用于发现人血清中以前未测量到的环境化学物质。使用非靶向数据采集（全扫描 MS 分析），我们能够在 20 名妊娠中期孕妇的血清样本中筛选环境有机酸（EOAs）。我们将 EOAs 定义为具有至少一个可离解质子的商业上使用的环境有机化合物。EOAs 包括环境酚类、邻苯二甲酸代谢物、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。我们经过验证的方法使用固相萃取、C18 柱反相色谱、梯度洗脱、负电喷雾电离和自动串联 MS（MS/MS）数据采集，以最大限度地提高真实阳性率。我们使用安捷伦 MassHunter Qualitative Analysis 软件识别“可疑 EOAs”，从每个样品运行中生成的化学公式与我们从多个环境文献来源组装的 693 种独特 EOAs 数据库中的分子公式相匹配。我们在数据库中发现了 282 种（41%）EOAs 的潜在匹配物。在至少 75%的样本中检测到这些可疑 EOAs 中的 65 种；在国家健康和营养检查调查中，目前仅监测到其中 19 种化合物。我们通过 LC-QTOF/MS 使用通过 LC-MS/MS 开发的靶向方法确认了三种可疑 EOAs 中的两种，报告了在孕妇血清中首次确认二苯甲酮-1 和双酚 S。我们的可疑筛选工作流程提供了一种全面扫描人体环境化学暴露的方法。这可以提供更好的暴露信息来源，有助于改善对工业化学品的暴露和风险评估。
