A quantitative framework for optimization, interpretation, and quality control of the PFAS total oxidizable precursor...

The total oxidizable precursor (TOP) assay is widely used to estimate oxidizable per- and polyfluoroalkyl substance (PFAS) precursors not captured by targeted analysis. However, inconsistent reaction conditions and the absence of practical quality control strategies limit its analytical reliability and interlaboratory comparability. In this study, a quantitative framework was developed to improve TOP assay performance through systematic optimization, precursor-product conversion mapping, and direct performance verification. Evaluation of sixteen combinations of persulfate and sodium hydroxide concentrations demonstrated that oxidation efficiency was more consistently described by reagent concentration ratio than by absolute reagent levels within the investigated design space, with a local maximum in total molar conversion yield observed at a [K₂S₂O₈]/[NaOH] ratio of approximately 0.2. Under optimized conditions, a molar conversion yield matrix was established for 27 PFAS precursors and 19 oxidation products, providing a practical quantitative reference framework for interpreting precursor transformation behavior. A conversion-based quality control approach using post-oxidation spiked recovery was further introduced to directly assess oxidation efficiency during routine sample analysis without modification of standard LC-MS workflows. Application to representative aqueous samples produced post-oxidation spiked recoveries of 70-140% under the investigated conditions, demonstrating the feasibility of the proposed quality control framework. The proposed framework improves the robustness, reproducibility, and interpretability of the TOP assay and provides a practical basis for more standardized PFAS precursor assessment.