The use of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to quantitate surface-protein binding interactions is explored using the peptide-porcine insulin and a variety of commercially available polymers. We show that a standard-additions plot of porcine-insulin surface concentration versus porcine-insulin MALDI ion signal is linear over a range of surface concentrations from 100 ng/cm(2) to 800 ng/cm2. Further, similar to previous studies, we demonstrate that the positive x-intercepts of these standard-additions plots correlate with the polymer-porcine insulin retention affinities as established using I-125-labeled-porcine insulin. Additional novel studies demonstrate that the polymer-porcine insulin retention affinities determined from the standard-additions plots are independent of both the MALDI matrix and the desorption/ionization wavelength. Finally, it is shown that the polymer-porcine-insulin adsorption affinity can be established by measuring the porcine-insulin MALDI ion signal resulting from adsorbed peptide and by using the standard-additions plot for quantitation. Cumulatively, these studies suggest MALDI mass spectrometry can be effectively employed to quantitate polymer-protein binding interactions.