1. is similar in its response to matrix effect as the analyteof-interest. Obviously, in this respect a stable isotope (having the same physicochemical properties) would be ideal. Still, their limited availability and cost leads to the next best option, which is a structural analogue. The traditional disadvantage of structural analogues (not necessarily co-eluting with the analyte and therefore experiencing different ionization conditions) is overcome by the continuous PCIS signal over time. 2. is commercially available and affordable. It should be considered that the consumption of ISTD per sample will be higher if it is infused as compared to if it is added to the sample. 3. ideally, has a commercially available and affordable SIL, which can be used as a spiked ISTD to correct for sample preparation recovery or injection volume. Since a spiked ISTD can also suffer from differences in matrix effect between samples, it should also be corrected by a PCIS. To prevent multiplication of errors, it is even more important for a spiked ISTD that the similarity in response to matrix effect between ISTD and PCIS is very close to perfect (as a stable isotope would be). 4. is stable in solution for at least the time of an analysis batch at lab temperature (or, if necessary, with appropriate cooling). Namely, degradation of a PCIS during a batch would result in an increasing overcorrection. 5. is measurable with a specific signal. When measuring in multiple reaction monitoring (MRM) mode, it should have a selective MRM transition, giving limited to no signal in matrix without infusing the PCIS candidate and should not interfere with the MRM transitions of the analytes. The presence of a non-endogenous atom, like fluorine, can help in achieving that.