University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Straße 38, 1090, Vienna, Austria; University of Vienna, Vienna Doctoral School in Chemistry, Währinger Straße 42, 1090, Vienna, Austria.
University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry, Währinger Straße 38, 1090, Vienna, Austria; Exposome Austria, Research Infrastructure and National EIRENE Hub, Austria.
Anal Chim Acta. 2023 Oct 23;1279:341740. doi: 10.1016/j.aca.2023.341740. Epub 2023 Aug 19.
The chemical exposome consists of environmental exposures experienced throughout a lifetime but to date analytical approaches to investigate the plethora of low-abundance chemicals remain very limited. Liquid chromatography high-resolution mass spectrometry (HRMS) is commonly applied in untargeted exposome-wide analyses of xenobiotics in biological samples; however, human biomonitoring approaches usually utilize targeted low-resolution triple quadrupole (QQQ) mass spectrometry tailored to a small number of chemicals. HRMS can cover a broader chemical space but the detection of molecules from low-level exposure amidst a background of highly-abundant endogenous molecules has proven to be difficult. In this study, a triple quadrupole (QQQ) and a high-resolution mass spectrometer (HRMS) with identical chromatography were utilized to determine the limits of quantitation (LOQ) of >100 xenobiotics and estrogenic hormones in pure solvent and human urine. Both instrumental platforms are currently applied in exposure assessment studies and were operated in their most frequently used acquisition mode (full scan for HRMS and multiple reaction monitoring for QQQ) to mimic typical applications. For HRMS analyses, the median LOQ was 0.9 and 1.2 ng/mL in solvent and urine, respectively, while for low-resolution QQQ measurements, the median LOQ was 0.1 and 0.2 ng/mL in solvent and urine, respectively. To evaluate the calculated LOQs in complex biological samples, spot urine samples from 24 Nigerian female volunteers were investigated. The higher LOQ values for HRMS resulted in less quantified low-abundance analytes and decreased the number of compounds detected below the LOQ. Even at chronic low-dose exposure, such compounds might be relevant for human health because of high individual toxicity or potential mixture effects. Nevertheless, HRMS enabled the additional screening for exposure to unexpected/unknown analytes, including emerging compounds and biotransformation products. Therefore, a synergy between high- and low-resolution mass spectrometry may currently be the best option to elucidate and quantify xenobiotics in comprehensive exposome-wide association studies (ExWAS).
化学暴露组学由一生中经历的环境暴露组成，但迄今为止，用于研究大量低丰度化学物质的分析方法仍然非常有限。液相色谱-高分辨率质谱（HRMS）通常用于生物样本中新型污染物的暴露组学全分析；然而，人体生物监测方法通常利用针对少数化学物质定制的靶向低分辨率三重四极杆（QQQ）质谱。HRMS 可以覆盖更广泛的化学空间，但在高度丰富的内源性分子背景下检测低水平暴露的分子已被证明具有挑战性。在这项研究中，利用具有相同色谱的三重四极杆（QQQ）和高分辨率质谱（HRMS）来确定 100 多种新型污染物和雌激素在纯溶剂和人尿中的定量下限（LOQ）。这两种仪器平台目前都应用于暴露评估研究，并以最常用的采集模式（HRMS 为全扫描，QQQ 为多重反应监测）运行，以模拟典型应用。对于 HRMS 分析，溶剂和尿液中的中位数 LOQ 分别为 0.9 和 1.2ng/mL，而对于低分辨率 QQQ 测量，溶剂和尿液中的中位数 LOQ 分别为 0.1 和 0.2ng/mL。为了评估复杂生物样本中计算出的 LOQ，研究了 24 名尼日利亚女性志愿者的尿样。HRMS 的较高 LOQ 值导致较少定量的低丰度分析物，并减少了低于 LOQ 检测到的化合物数量。即使在慢性低剂量暴露下，由于个体毒性高或潜在的混合物效应，此类化合物也可能与人类健康相关。然而，HRMS 能够额外筛选出意外/未知的分析物的暴露情况，包括新兴化合物和生物转化产物。因此，高分辨率和低分辨率质谱之间的协同作用可能是阐明和量化综合暴露组学全关联研究（ExWAS）中新型污染物的最佳选择。
