Methods of characterizing an analyte of interest are provided. The methods can involve using a population of nanoparticles (e.g., magnetic ferrite nanoparticles) as a matrix for matrix-assisted laser desorption ionization (MALDI) mass spectrometry. The size, shape, and composition of the nanoparticles can be selected in view of a variety of factors, including the nature of the analyte of interest, the desired characteristics of the mass spectrum, the nature of the energy directed onto the target composition, and combinations thereof. The nanoparticle matrix can enhance MALDI analysis by providing a cleaner mass spectral background and/or inducing abundant fragmentation of analyte ions by in-source decay (ISD). The nanoparticles are also versatile and selective; the nanoparticle matrix can be tuned to render the matrix particles compatible with an analyte of interest and/or improve selectivity for an analyte of interest.