Nontargeted Analysis Reveals Organofluorine Pharmaceutical Compounds Responsible for Formation of Toxic Disinfection Byproducts in a Drinking Water Treatment Plant in China

Toxic disinfection byproducts (DBPs) formed during chlorination are a significant concern for drinking water safety. These compounds were analyzed using nontargeted methods, and their chemical formulas and structures were determined through tandem mass spectrometry combined with a novel fragmental chain characterization (FCC) algorithm. This FCC algorithm significantly improved annotation rates, achieving a four-fold increase compared to traditional mass spectral matching strategies. Transformation linkages were identified between precursor compounds and DBPs, based on their shared fragmental chains. Using this advanced nontargeted analysis approach, we identified organofluorine precursors as key contributors to the formation of toxic DBPs in chlorinated water. These findings were validated using chemical standards, including fluoroquinolone antibiotics (e.g., enrofloxacin and difloxacin) and fluorosteroids (e.g., fluocinolone acetonide and triamcinolone). Fluoroquinolone-derived DBPs were found to be 2.5 times more toxic after chlorination, exceeding the 1.5 times overall toxicity increase observed in actual water samples. Fluorosteroids showed smaller toxicity increases (1.3–1.5 times), but their conversion rates in real water were 1.7–2.3 times higher than in laboratory conditions. This study highlights the role of organofluorine precursors in DBP formation and provides an innovative method to identify unknown DBPs, elucidate their formation pathways, and trace their sources, advancing water treatment safety.