This application note highlights the LC/MS/MS analysis of PFAS compounds according to the European Union Water Framework Directive 2020/2184. It demonstrates how the PerkinElmer QSight® 420 LC/MS/MS System using a large volume direct injection can determine and quantify the latest 20 PFAS compounds added to the Directive 2020/2184. The method shows a comprehensive solution including details related to LC and MS Methods and provides information on the required steps to prevent any possible contamination.