Per- and polyfluoroalkyl substances (PFAS) have excellent resistant properties and are thus widely used in packaging materials, firefighting foams and many other uses. As PFAS have been found in virtually every environmental matrix including drinking water supplies, making monitoring critical to ensure safety. Here, a comprehensive quantitative method for a suite of PFAS compounds was developed for analysis of water samples on the SCIEX 7500 system. This high sensitivity system provided S/N gains of ~5.5x on average across the 54 compounds analyzed versus the SCIEX 6500+ system.