Department of Environmental Health Science, Yale School of Public Health, New Haven, CT, USA.
Agilent Technologies, Inc., Santa Clara, CA, USA.
Sci Total Environ. 2023 Jul 20;883:163579. doi: 10.1016/j.scitotenv.2023.163579. Epub 2023 Apr 24.
A small subset of per- and polyfluoroalkyl substances (PFAS) are routinely screened in human blood. These compounds generally explain <50 % of the total PFAS in human blood. The percentage of known PFAS in human blood has been decreasing as replacement PFAS and more complex PFAS chemistries are introduced to the market. Most of these novel PFAS have not been previously identified. Non-targeted methods are required to characterize this "dark matter" PFAS. Our objective was to apply non-targeted PFAS analysis to human blood to gain an understanding about the sources, concentrations, and toxicity of these compounds. A high-resolution tandem mass spectrometry (HRMS) and software workflow for PFAS characterization in dried blood spots is reported. Dried blood spots are a less invasive collection technique compared to venous blood draws, allowing collection from vulnerable populations. Biorepositories of archived dried blood spots are available internationally from newborns and present opportunities to study prenatal exposure to PFAS. In this study, dried blood spot cards were analyzed using iterative MS/MS by liquid chromatography HRMS. Data processing was conducted using FluoroMatch Suite including a visualizer tool that presents homologous series, retention time vs m/z plots, MS/MS spectra, feature tables, annotations, and fragments for fragment screening. The researcher performing data-processing and annotation was blinded to the fact that standards were spiked in, and was able to annotate 95 % of standards spiked on dried blood spot samples, signifying a low false negative rate using FluoroMatch Suite. A total of 28 PFAS (20 standards and 4 exogenous compounds) were detected across five homologous series with Schymanski Level 2 confidence. Of these 4, 3 were perfluoroalkyl ether carboxylic acids (PFECA), a chemical class of PFAS which is increasingly being detected in environmental and biological matrices but is not currently screened in most targeted analysese. A further 86 potential PFAS were detected using fragment screening. PFAS are extremely persistent and widespread yet remain largely unregulated. Our findings will contribute to an improved an understanding of exposures. Application of these methods in environmental epidemiology studies have the potential to inform policy with regards to PFAS monitoring, regulation, and individual-level mitigation strategies.
一小部分的全氟和多氟烷基物质（PFAS）通常在人体血液中进行常规筛查。这些化合物通常只能解释人体血液中总 PFAS 的 <50%。随着市场上引入替代 PFAS 和更复杂的 PFAS 化学物质，人体血液中已知 PFAS 的比例一直在下降。这些新的 PFAS 中的大多数以前没有被识别出来。需要使用非靶向方法来描述这种“暗物质”PFAS。我们的目标是应用非靶向 PFAS 分析来研究人体血液，以了解这些化合物的来源、浓度和毒性。本文报道了一种用于在干血斑中进行 PFAS 特征分析的高分辨率串联质谱（HRMS）和软件工作流程。与静脉采血相比，干血斑是一种侵入性较小的采集技术，允许从弱势群体中采集。国际上有存档干血斑的生物库，可用于研究产前接触 PFAS。在这项研究中，使用液相色谱高分辨串联质谱（HRMS）进行迭代 MS/MS 对干血斑卡进行分析。使用 FluoroMatch Suite 进行数据处理，其中包括一个可视化工具，该工具提供同系物、保留时间与 m/z 图、MS/MS 光谱、特征表、注释和碎片筛选的片段。进行数据处理和注释的研究人员对标准品被添加到样本中的事实不知情，并且能够注释 95%添加到干血斑样本中的标准品，这表明使用 FluoroMatch Suite 具有较低的假阴性率。在五个同系物中检测到 28 种 PFAS（20 种标准品和 4 种外源性化合物），置信度为 Schymanski 等级 2。其中 3 种是全氟烷基醚羧酸（PFECA），PFECA 是一类 PFAS，越来越多地在环境和生物基质中被检测到，但目前大多数靶向分析中都没有对其进行筛查。使用碎片筛选还检测到另外 86 种潜在的 PFAS。PFAS 极为持久且广泛存在，但仍在很大程度上不受监管。我们的研究结果将有助于更好地了解接触情况。这些方法在环境流行病学研究中的应用有可能为 PFAS 监测、监管和个人层面的缓解策略提供信息。
