Through this mechanistic study we were able to explain how the pH can play an important role and how, by adjusting it, it is possible to improve significantly the analytical performances thanks to a better discrimination of the specific vs. nonspecific response. It also allowed us to demonstrate that the double masking does not prevent autocatalysis from working despite the fact that two equivalents of H2O2 are needed to completely deprotect the probe. Furthermore, as illustrated with the selection of a better redox cycler for the design of probe P4, it is clear that there is room to further improve the analytical performances of the system.