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.