The study of per-and polyfluoroalkyl substance (PFAS) pollutants has been extended from the early focus on all-carbon perfluorocarboxylates (PFCAs, CnF2n+1-COO -) and perfluoroalkane sulfonates (PFSAs, CnF2n+1-SO3 -) to a large variety of "novel" structures with various heteroatoms, branching patterns, and chain lengths. For example, many fluorinated ether structures have been detected in water and soil worldwide and shown various toxicities. The belated attention to these structures is primarily attributed to (1) the information gap between fluorine chemistry and environmental chemistry and (2) the lack of analytical standards for targeted analysis. For the detection of telomer (CnF2n+1-(CH2)m-X, X=highly diverse organic functional groups) and sulfonamide (CnF2n+1-SO2NH-X) surfactants, total oxidizable precursor (TOP) assay has been widely applied. The H atoms in the "precursor" molecules allow oxidation by hydroxyl radicals (HO•, generated from persulfate at pH>12 at 85℃), yielding one or multiple PFCAs for targeted analysis. Our lab further modified the reaction condition (e.g., [NaOH]:[K2S2O8]=5:1 and 120 ℃), extended the substrate scope (e.g., CnF2n+1-(CH2)2-COO -, CnF2n+1-(CH2)2-SO3 -, and HCnF2n-COO -with variable n), and quantified short-chain products (e.g., CF3-COO -, C2F5-COO -, and -OOC-CF2-COO -). Notably, structures with only one C-H bond in HCF2and multiple C-H bonds in -(CH2)2showed distinct transformation patterns. A previous TOP assay of various fluoro ether structures by Zhang et al. found that only H-containing structures could be converted by HO•, but the product information remained largely unknown. The above findings reflect several limitations (but not necessarily disadvantages) of the current TOP assay. First, HO• oxidation requires H atoms in the precursor and does not transform either PFCAs or PFSAs. In contrast, oxidation using sulfate radicals (SO4 -•, generated from persulfate and preserved at pH<2) is a well-adopted pretreatment for water sample analysis. For example, the measurement of total phosphorus uses acidic persulfate digestion to convert various organic phosphate esters into orthophosphate. SO4 -• can also oxidize PFCAs via decarboxylation. Second, "novel" PFAS structures do not necessarily produce linear PFCAs, which the current TOP assay relies on. However, while the reaction kinetics under oxidative conditions have been extensively quantified, the structural transformation of emerging PFAS has not been adequately understood. Hence, it is important to elucidate the transformation of novel PFAS "precursors" by both SO4 -• and HO• for environmental detection and source tracking.