UFZ - Helmholtz Centre for Environmental Research , Department of Effect-Directed Analysis, Permoserstr. 15, D-04318 Leipzig, Germany.
Environ Sci Technol. 2015 Mar 3;49(5):2959-68. doi: 10.1021/es503640k. Epub 2015 Feb 12.
The identification of unknown compounds remains one of the most challenging tasks to link observed toxic effects in complex environmental mixtures to responsible toxicants in effect-directed analysis (EDA). Here, a workflow is presented based on nontarget liquid chromatography-high resolution mass spectrometry (LC-HRMS) starting with molecular formulas determined in a previous study. A compound database search (ChemSpider) was performed to retrieve candidates for each formula. Subsequently, the number of candidates was reduced by applying MS-, physical-chemical, and chromatography-based selection criteria including HRMS/MS fragmentation and plausibility, ionization efficiency with different ion sources and detection modes, acid/base behavior, octanol/water partitioning, retention time prediction and finally toxic effects (mutagenicity caused by aromatic amines). The workflow strongly decreased the number of possible candidates and resulted in the tentative identification of possible mutagens and the positive identification of the nonmutagen benzyl(diphenyl) phosphine oxide in a mutagenic fraction. The positive identification of mutagens was hampered by a lack of commercially available standards. The workflow is an innovative and promising approach and forms an excellent basis for possible further advancements.
鉴定未知化合物仍然是将复杂环境混合物中观察到的毒性效应与定向分析（EDA）中负责的毒性物质联系起来的最具挑战性的任务之一。在这里，提出了一个基于非靶向液相色谱-高分辨质谱（LC-HRMS）的工作流程，从先前研究中确定的分子公式开始。对每个公式进行了化合物数据库搜索（ChemSpider）以检索候选物。随后，通过应用基于 MS、物理化学和色谱的选择标准，包括 HRMS/MS 碎片和合理性、不同离子源和检测模式下的电离效率、酸碱行为、辛醇/水分配系数、保留时间预测，最终是毒性效应（芳香胺引起的致突变性），将候选物的数量减少。该工作流程大大减少了可能的候选物数量，并导致在致突变性馏分中对可能的致突变剂进行了暂定鉴定，并对阳性鉴定的非致突变性二苯膦氧进行了鉴定。由于缺乏市售标准，致突变剂的阳性鉴定受到阻碍。该工作流程是一种创新且有前途的方法，为可能的进一步发展奠定了良好的基础。
