Through analyzing mixtures of compounds of known gas-phase basicities, the importance of this property on the secondary ions emitted from a surface under primary ion bombardment is investigated. The aim is to obtain a greater understanding of the ionization mechanisms that occur in secondary ion mass spectrometry (SIMS). The commonly used matrix assisted laser desorption/ionization (MALDI) matrix 2,4,6-trihydroxyacetophenone (THAP) and a range of low molecular weight biomolecules were used to investigate whether analyte/matrix suppression effects that have been observed in analogous MALDI experiments were also present in static-SIMS. The outcome of the experiments demonstrates that strong suppression of the quasi-molecular signal of one molecule in a mixture can occur due to the presence of the other, with the gas-phase basicity of the compounds being a good indicator of the secondary ions detected. It is also demonstrated that the suppression of the quasi-molecular ion signal of a compound in a two-component mixture can be minimized by the inclusion of a third compound of suitable gas-phase basicity.