Electrospray ionization mass spectrometry (ESI-MS) is one of the most powerful ionization techniques for characterization of analytes in various areas. Polar solvents such as methanol， water and acetonitrile are commonly used for ESI-MS analysis， while nonpolar solvents such as hexane were usually considered as non-ESI-friendly solvents. Following our recent work on observation of ESI process from solid substrates using nonpolar solvents (Anal Chim Acta， 2018， 1004， 51-57)， the analytical properties of ESI-MS with solid substrates and nonpolar solvents were further systematically investigated in this study. Compared to the uses of polar solvents， our results revealed that nonpolar solvents could serve as extractants for enhanced detection of low-polar analytes from complex samples， and could serve as refrigerants for rapid freezing of samples such as peptides， proteins and protein-ligand complexes. Furthermore， nonpolar solvents could be used for formation of ammonia-transition-metal acetylacetonates complexes under ambient conditions.