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Environmental water screenings are regularly challenged by the number and diversity of chemical and biological targets in a given sample. Traditional chromatographic separation can be insufficient to discriminate between closely related compounds or meet established detection limits. The combination of the Bruker TargetScreener LC method with trapped ion mobility spectrometry via the Bruker timsTOF Pro system enables rapid discrimination of PFOS pollutants, including isomers, with significantly improved target detection sensitivity.