Highly polar trace organic compounds, which are persistent, mobile, and toxic (PMT) or are very persistent and very mobile (vPvM) in the aquatic environment, may pose a risk to surface water, ground water, and drinking water supplies. Despite the advances in liquid chromatography-mass spectrometry, there often exists an analytical blind spot when it comes to very polar chemicals. This study seeks to make a broad polarity range analytically accessible by means of serially coupling reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) to high-resolution mass spectrometry (HRMS). Moreover, a workflow is presented using optimized data processing of nontarget screening (NTS) data and subsequently generating candidate lists for the identification of very polar molecules via an open-access NTS platform and implemented compound database. First, key input parameters and filters of the so-called feature extraction algorithms were identified, and numerical performance indicators were defined to systematically optimize the data processing method. Second, all features from the very polar HILIC elution window were uploaded to the STOFF-IDENT database as part of the FOR-IDENT open-access NTS platform, which contains additional physicochemical information, and the features matched with potential compounds by their accurate mass. The hit list was filtered for compounds with a negative log D value, indicating that they were (very) polar. For instance, 46 features were assigned to 64 candidate compounds originating from a set of 33 samples from the Isar river in Germany. Three PMT candidates (e.g., guanylurea, melamine, and 1,3-dimethylimidazolidin-2-one) were illustratively validated using the respective reference standards. In conclusion, these findings demonstrate that polarity-extended chromatography reproducibly retards and separates (very) polar compounds from surface waters. These findings further indicate that a transparent and robust data processing workflow for nontarget screening data is available for addressing new (very) polar substances in the aqueous environment.

在水生环境中具有持久性、流动性和毒性 (PMT) 或极持久性和极易流动性 (vPvM) 的高极性痕量有机化合物可能对地表水、地下水和饮用水供应构成风险。尽管液相色谱-质谱法取得了进步，但在涉及极性很强的化学品时，往往存在分析盲点。本研究旨在通过将反相液相色谱 (RPLC) 和亲水相互作用液相色谱 (HILIC) 串联耦合到高分辨率质谱 (HRMS) 来实现广泛的极性范围分析。而且，使用非目标筛选 (NTS) 数据的优化数据处理，随后通过开放访问的 NTS 平台和实施的化合物数据库生成用于识别极极性分子的候选列表，呈现了一个工作流程。首先，确定了所谓特征提取算法的关键输入参数和过滤器，并定义了数值性能指标，以系统地优化数据处理方法。其次，来自极极性 HILIC 洗脱窗口的所有特征都上传到 STOFF-IDENT 数据库，作为 FOR-IDENT 开放访问 NTS 平台的一部分，该平台包含额外的物理化学信息，并且特征与潜在化合物的准确质量相匹配。命中列表被过滤为负对数的化合物 确定了所谓特征提取算法的关键输入参数和过滤器，并定义了数值性能指标，以系统地优化数据处理方法。其次，来自极极性 HILIC 洗脱窗口的所有特征都上传到 STOFF-IDENT 数据库，作为 FOR-IDENT 开放访问 NTS 平台的一部分，该平台包含额外的物理化学信息，并且特征与潜在化合物的准确质量相匹配。命中列表被过滤为负对数的化合物 确定了所谓特征提取算法的关键输入参数和过滤器，并定义了数值性能指标，以系统地优化数据处理方法。其次，来自极极性 HILIC 洗脱窗口的所有特征都上传到 STOFF-IDENT 数据库，作为 FOR-IDENT 开放访问 NTS 平台的一部分，该平台包含额外的物理化学信息，并且特征与潜在化合物的精确质量相匹配。命中列表被过滤为负对数的化合物 来自极极性 HILIC 洗脱窗口的所有特征都上传到 STOFF-IDENT 数据库，作为 FOR-IDENT 开放访问 NTS 平台的一部分，该平台包含额外的物理化学信息，并且特征与潜在化合物的精确质量相匹配。命中列表被过滤为负对数的化合物 来自极极性 HILIC 洗脱窗口的所有特征都上传到 STOFF-IDENT 数据库，作为 FOR-IDENT 开放访问 NTS 平台的一部分，该平台包含额外的物理化学信息，并且特征与潜在化合物的精确质量相匹配。命中列表被过滤为负对数的化合物D值，表明它们是（非常）极性的。例如，46 个特征被分配给来自德国伊萨尔河 33 个样本的 64 个候选化合物。三种 PMT 候选物（例如，鸟苷脲、三聚氰胺和 1,3-二甲基咪唑烷-2-one）使用各自的参考标准进行了说明性验证。总之，这些发现表明，极性扩展色谱可重现地延迟和分离（非常）极性化合物与地表水。这些发现进一步表明，非目标筛选数据的透明和强大的数据处理工作流程可用于解决水性环境中的新（极）极性物质。