The limited use of PCIS might be explained by an underappreciation of the problem of matrix effect, a reluctance to abandon the widely recognized method for matrix effect correction (i.e. adding SIL-ISTDs to all samples), an underestimation of the great potential of PCIS or a lack of guidance on how to incorporate PCIS in existing or new LC-MS methods. With the current paper, we aim to remove these possible objections and demonstrate that PCIS is a solution to elevate metabolomics from semi-quantification to absolute quantification. Using an LC-MS/MS method for measuring metabolites related to the endocannabinoid system in plasma, for which SIL standards were available and which suffer from ion suppression , we will provide strategies to incorporate PCIS into LC-MS/MS methods. We will discuss characteristics of a good PCIS candidate and the optimization of its concentration. Various approaches to evaluate the PCIS performance will be demonstrated and processes for which a PCIS cannot correct will be discussed. Finally, we will show the potential of PCIS as a replacement of SIL-ISTDs and as a tool enabling absolute quantification based on a calibration curve of standards in neat solution instead of matrix.