Non-targeted analysis (NTA), including both suspect screening analysis (SSA) and unknown compound analysis, has gained increasing popularity in various fields for its capability in identifying new compounds of interests. Current major challenges for NTA SSA are that (1) tremendous effort and resources are needed for large-scale identification and confirmation of suspect chemicals and (2) suspect chemicals generally show low matching rates during identification and confirmation processes. To narrow the gap between these challenges and smooth implementation of NTA SSA methodology in the biomonitoring field, we present a thorough SSA workflow for the large-scale screen, identification, and confirmation of industrial chemicals that may pose adverse health effects in pregnant women and newborns. The workflow was established in a study of 30 paired maternal and umbilical cord serum samples collected at delivery in the San Francisco Bay area. By analyzing LC-HRMS and MS/MS data, together with the assistance of a combination of resources including online MS/MS spectra libraries, online in silico fragmentation tools, and the EPA CompTox Chemicals Dashboard, we confirmed the identities of 17 chemicals, among which monoethylhexyl phthalate, 4-nitrophenol, tridecanedioic acid, and octadecanedioic acid are especially interesting due to possible toxicities and their high-volume use in industrial manufacturing. Similar to other previous studies in the SSA field, the suspect compounds show relatively low MS/MS identification (16%) and standard confirmation (8%) rates. Therefore, we also investigated origins of false positive features and unidentifiable suspected features, as well as technical obstacles encountered during the confirmation process, which would promote a better understanding of the flaw of low confirmation rate and encourage gaining more effective tools for tackling this issue in NTA SSA.

中文翻译：

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工业化学品人血清疑似筛查分析的大规模实施和缺陷调查。


非靶向分析（NTA），包括可疑筛选分析（SSA）和未知化合物分析，因其识别新目标化合物的能力而在各个领域越来越受欢迎。 NTA SSA 当前面临的主要挑战是（1）需要巨大的努力和资源来大规模识别和确认可疑化学品；（2）可疑化学品在识别和确认过程中通常表现出较低的匹配率。为了缩小这些挑战之间的差距，并在生物监测领域顺利实施 NTA SSA 方法，我们提出了一套完整的 SSA 工作流程，用于大规模筛查、识别和确认可能对孕妇和新生儿健康造成不良影响的工业化学品。该工作流程是在对旧金山湾区分娩时收集的 30 份配对母体和脐带血清样本的研究中建立的。通过分析 LC-HRMS 和 MS/MS 数据，并结合在线 MS/MS 谱图库、在线计算机碎裂工具和 EPA CompTox 化学品仪表板等资源组合的帮助，我们确认了 17 种化学物质的身份，其中其中邻苯二甲酸单乙基己酯、4-硝基苯酚、十三烷二酸和十八烷二酸由于可能的毒性及其在工业制造中的大量使用而特别令人感兴趣。与 SSA 领域之前的其他研究类似，可疑化合物的 MS/MS 鉴定率 (16%) 和标准确认率 (8%) 相对较低。 因此，我们还调查了误报特征和无法识别的可疑特征的起源，以及确认过程中遇到的技术障碍，这将有助于更好地理解低确认率的缺陷，并鼓励获得更有效的工具来解决这一问题。 NTA SSA。