A solution to this problem of non-coeluting ISTDs was already proposed by They demonstrated that by continuously adding a SIL drug after the LC column and before entering the MS, as a post-column infused standard (PCIS), its signal could correct for ion suppression on both the drug and its earlier eluting metabolite. This was not possible when the same compound was added to the samples as a spiked ISTD, because the two analytes suffered from ion suppression to a different extent. After this first publication, the innovative PCIS technique for matrix effect correction has only sparsely been adopted , even though it has great potential to overcome practical issues in quantitation.