Multicriteria approach to select polyaromatic river mutagen candidates

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.