Desorption ionization on silicon mass spectrometry (DIOS-MS) allows for the detection of low molecular weight species from fluid samples. However, this method remains scarcely used for clinical diagnosis likely because of a lack of knowledge about the desorption/ionization mechanism as well as about the interplay between the surface and analyte properties which are effective in desorption/ionization, impeding the optimization of the DIOS-MS analysis. Herein, the normalized intensity of the DIOS-MS peaks at [M+H]