Non-targeted screening of per- and polyfluoroalkyl substances: Advanced methods, challenges, and environmental health.

Per- and polyfluoroalkyl substances (PFAS), a class of synthetic fluorine-containing organic compounds, pose a serious threat to the ecological environment and human health due to their persistence, bioaccumulation, and extensive toxicity. Non-targeted screening (NTS) is a key method for identifying and determining unknown PFAS, which is crucial to the understanding of their exposure pathway and health risks. Hence, this review focuses on NTS techniques for PFAS in the environment. Firstly, high-resolution mass spectrometry and ion mobility innovations enabling novel PFAS/isomer identification are evaluated. Afterwards, pretreatment optimization (e.g., solid-phase extraction and emerging adsorbents) is summarized by analyzing the advantages of each method and the challenges posed by the limited datasets, while also outlining their applicable scenarios. Analytical challenges from structural complexity (short-chain substitutes and ether-based fluorine-modulated polymers) and matrix effects are discussed. Lastly, practical implications for environmental health and the future development potential of NTS technologies for PFAS are presented. Overall, this review proposes a science-based framework for monitoring and regulatory prioritization, with the expectation of supporting PFAS management and mitigation.