In MALDI MS, occasionally when the analyte concentration in a sample reaches certain levels, matrix ions can be partially or even completely suppressed. In addition, suppression of one analyte ion by another analyte ion formed from the same or a different analyte can also occur. Because MALDI MS samples are heterogeneous, and samples of an analyte prepared using the same recipe can give variable analysis results, special experimental design such as closely matched controls, experiments with standard samples and statistically meaningful amount of data are needed if MALDI MS is to be used for analyte quantification and for the determination of analyte purity. In the context of ion pair thermal model, ion suppression is conceivable. The total number of ion pairs that have sufficient energy to generate detectable free ions by the extraction potential is roughly constant. Taking the suppression of matrix ions by analyte ions for an example, when the concentration of an analyte in the sample increases, the number of high energy ion pairs involving an ion from the analyte in the plume increases. This increase is at the cost of the high energy ion pairs involving matrix ions, which become undetectable species via mechanisms such as neutralization via proton transfer and loss of kinetic and vibrational energy.