Anthropogenic PFAS or Natural Products? Natural Products Cause Overestimation of C2–C5 Perfluoroalkyl Carboxylic Acid Levels

The increasing environmental concentrations of C2-C5 perfluoroalkyl carboxylic acids (PFCAs) have raised concerns about their global threat. However, analytical interference has been reported to cause overestimation of PFCA concentrations. Recently, we discovered that a human metabolite, γ-carboxyethyl hydroxychroman, caused overestimation of the perfluoropentanoic acid (PFPeA) concentration by 454 times due to its similar retention time and ion pair mass with those of PFPeA in low-resolution mass spectrometry. Using this interference mechanism, we developed a semitargeted screening method to identify all possible interferents of C2-C5 PFCAs in surface water, groundwater, wastewater, soil, fish, and human serum samples. Nine interferents were discovered, resulting in a 2.18-454 times overestimate of the concentration. Through the screening of 289 serum samples, most interferents were recognized as carboxylic acid natural products, possibly originating from human metabolism. Adjustment of the mobile phase to acidic or use of a pentafluorophenyl column can eliminate interferences. Retrospective screening against both 41 studies from 16 countries with significant concentrations of C2-C5 PFCAs and a public data repository revealed the global prevalence of analytical interferents. Our findings highlighted the necessity to re-evaluate the concentrations of C2-C5 PFCAs and subsequently their migration, transformation, and bioconcentration properties to accurately understand their environmental significance.