The quest for the perfect "total PFAS" method: how can the total oxidisable precursor (TOP) assay be made reliable?

Per- and polyfluoroalkyl substances (PFAS) make up a large and complex class of manmade chemicals. They have been widely used in numerous industrial branches and are incorporated into many consumer products. Today, there is a consensus on the fact that PFAS are present in all environmental compartments and that populations all over the world are subjected to them via internal exposure. It has been estimated that thousands of individual PFAS have been manufactured and marketed since the 1950s, to which impurities present in commercial products and intermediate environmental transformation products should be added. Since it is unrealistic to be able to individually identify, detect and quantify all the PFAS present in a sample, several analytical approaches have been developed to assess the presence of "hidden/unseen" PFAS. One of these, known as the total oxidisable precursor (TOP) assay, was first described in 2012. Basically, it converts some PFAS, hereafter referred to as precursors, into stable terminal products readily measurable by routine target methods. This review is based on more than 100 studies in which the original TOP assay was simply applied or optimised. The review found that the TOP assay was selective, sensitive, applicable to many matrices, useful within a forensic context, inexpensive, and easy to implement and has been assessed in the literature on a wide range of precursors. However, this method comprises many subtleties and has some flaws that operators should be made aware of so that they may be addressed as far as possible. Finally, this review tries to lay the foundations for better practices and quality assurance/quality control measures, in order to improve accuracy and reliability of TOP assay results.