To identify mechanisms affecting the stability of ion-sensitive field effect transistors (ISFETs) we investigated the penetration of water and ions into reoxidized nitrided oxide (RNO) which is known to have a higher resistance than silicon dioxide to the diffusion of impurities such as H2O, H+ and OH-. Electrolyte-oxide-semiconductor (EOS) structures with reoxidized nitrided oxide as dielectric were biased with different voltages. Metal-oxide-semiconductor capacitors were then fabricated incorporating these oxides. The charge trapping and the interface state generation susceptibility of reoxidized nitrided oxide after avalanche electron injection were compared for different capacitors. The increase in electron trapping observed for capacitors having reoxidized nitrided oxide exposed to acidic solution and stressed with negative bias to silicon is attributed to penetration of protons. This indicates that proton penetration and drift of protons into the insulator of the ISFET could lead to instability problems.