6. is easily fragmentable to the selective fragment. The most selective MRM transition may not be the most sensitive MRM transition and might require a higher concentration to give a stable PCIS signal. However, as discussed in the next section, a too high PCIS concentration can cause (significant) matrix effect by itself, resulting in a lower sensitivity for the analytes-of-interest 7. preferably has [M+H] + or [M-H] -as the main ion with limited or no adduct formation or in-source fragmentation. This is because using an adduct may cause a higher variability in signal and if adduct formation is significant, the signal of the (de)protonated ion may be less stable. However, when quantifying an analyte based on its adduct, a PCIS forming the same adduct would be preferable. Considering these characteristics, fluorinated anandamide (2F-AEA) was selected as a PCIS candidate for DHEA, SEA, LEA, OEA, PEA and AEA. It was anticipated that NADA and 2-AG would probably require an alternative PCIS, but for this example we will focus only on one PCIS.