Targeted chemical analyses have long provided gold-standard monitoring data that support exposure science and environmental epidemiology studies and eventual risk-based decisions. Despite this demonstrated utility, the advent of exposomics in 2005 yielded widespread recognition that “all” exposures encapsulate vastly more than the hundreds of routinely monitored, targeted chemical analytes [1]. To address this gap, non-targeted analysis (NTA) methods that utilize high-resolution mass spectrometry (HRMS) have emerged as the primary analytical tools for examining chemical stressors and stress response markers without a priori knowledge of sample content. These methods enable more comprehensive characterization of the exposome at both individual (e.g., analyzing a blood sample from a person) and community (e.g., tracking chemical fingerprints in wastewater) levels. As examples of successful implementation of NTA methods, recent applications have characterized the widespread presence of previously unidentified per- and polyfluoroalkyl substances (PFAS) in New Jersey soils [2], linked air pollution exposure to unique metabolic markers and pathways underlying the pathogenesis of cardiopulmonary disease [3], and identified potentially toxic environmental contaminants in the sera of pregnant women [4] and in human breastmilk [5].

长期以来，针对性化学分析一直提供黄金标准监测数据，支持暴露科学和环境流行病学研究以及最终基于风险的决策。尽管这已被证明是有用的，但 2005 年暴露组学的出现引起了广泛的认识，即“所有”暴露所包含的远远超过数百种常规监测的目标化学分析物 [1]。为了解决这一差距，利用高分辨率质谱 (HRMS) 的非靶向分析 (NTA) 方法已成为在不事先了解样品内容的情况下检查化学应激源和应激反应标记物的主要分析工具。这些方法能够在个体（例如，分析人的血液样本）和社区（例如，跟踪废水中的化学指纹）水平上对暴露组进行更全面的表征。作为成功实施 NTA 方法的例子，最近的应用表明新泽西州土壤中广泛存在以前未识别的全氟烷基物质和多氟烷基物质 (PFAS) [2]，将空气污染暴露与独特的代谢标志物和心肺疾病发病机制相关联。疾病 [3]，并在孕妇血清 [4] 和人类母乳 [5] 中发现了潜在的有毒环境污染物。