Uncovering Overlooked Fluorinated Compounds by Multi-Strategy Nontarget Screening in an Urban River System in China

Fluorinated compounds, including per- and polyfluoroalkyl substances (PFAS), are of increasing environmental concern, yet current monitoring approaches capture only a small fraction of their chemical diversity. We developed a multistrategy nontarget screening framework centered on a curated high-resolution MS/MS library of 7096 fluorinated compounds. This framework integrates target analysis, database matching, homologue screening, molecular networking, and reaction library-based annotation of potential transformation products. Applied to the Liuyang River, a representative urban watershed in China, we identified 106 fluorinated compounds. Among them, 36 PFAS were confirmed and quantified by targeted analysis, revealing PFAS spatiotemporal trends and associated drivers. Beyond these targets, nontarget screening identified additional fluorinated compounds including surfactants, pharmaceuticals, pesticides, industrial intermediates, and their transformation products. In total, 23 compounds had not been previously reported, including seven halogenated aromatic intermediates, nine homologues from three novel fluorotelomer ether carboxylic acid classes, and seven transformation products or structural analogues revealed by molecular networking. These results demonstrate blind spots in current PFAS monitoring and highlight the utility of multistrategy nontarget screening for uncovering the hidden diversity of fluorinated compounds in urban waters.