Solid-Phase Reactivity-Directed Extraction (SPREx): An Alternative Approach for Simultaneous Extraction, Identification, and Prioritization of Toxic Electrophiles Produced in Water Treatment Applications

Current strategies to assess water quality are ineffective at prioritizing the most toxic chemicals within a treated water sample. Although it is well known that oxidation byproducts (OBPs) from water treatment processes (e.g., chlorination and ozonation) are linked to adverse health outcomes such as skin diseases, reproductive toxicity, and various cancers, we are still unable to account for a large fraction of the toxicity drivers. Previous approaches utilize <i>in vitro</i> or <i>in vivo</i> assays to assess OBPs on an individual basis, which is too time- and resource-intensive considering the countless number of transformation byproducts of unknown toxicities that exist in treated waters. <i>In vitro</i> assays have also been developed to analyze the toxicity of OBPs in environmental mixtures, but these approaches do not provide identification information about the responsible toxicants. Furthermore, an additional challenge for OBP detection arises during the extraction and detection stages of analysis, as certain OBPs are typically lost using traditional extraction methods or are not detectable via liquid-chromatography-high-resolution mass spectrometry (LC-HRMS) without derivatization. To address these issues, we have developed the analytical assay <b>S</b>olid-<b>P</b>hase <b>R</b>eactivity-directed <b>Ex</b>traction (SPREx), which aims to provide an all-in-one evaluation for (i) <i>in chemico</i> toxicity screening, (ii) extraction, (iii) detection, and (iv) identification via LC-HRMS. The performance of SPREx was evaluated by testing different nucleophile probes for the capture and detection of 24 different carbonyl compounds, which serve as model electrophiles and are known OBPs that provide unique extraction and detection challenges. SPREx provided distinct advantages for extraction recoveries and was an effective screening tool for carbonyl detection and quantification in complex water matrices such as drinking water and wastewater.