Solid and viscous auxiliaries are often used for manufacturing granules,tablets,capsules and ointments in pharmaceutical industry,which emerge in the promising forms to maintain the stability and activity of various drugs by a variety of matrices.Ambient mass spectrometry(MS) with wooden-tip electrospray ionization(ESI) has been successfully developed for direct analysis of raw drug samples.However,matrix effect in such an ambient ESI-MS analysis on solid and viscous drugs has not yet been well understood.In this work,ionization responses to several modes of drugs in various viscous and solid matrices were investigated using a typical wooden-tip ESI-MS.Ionization responses were found to be related to the solubility of solid matrices.Ionic suppression and interference were observed in soluble solid matrices,while significant ionic interference was not generated in insoluble matrices.However,by adding spray solvent,insoluble matrices were changed in a viscous state suppressing spray ionization process.Further investigation revealed that ionization responses to analytes were decreased as a power function(r2>0.95) with the increase of matrix viscosity from 1 cP to 500 cP in this study.Therefore,this study may provide a good understanding for matrix effect and signal response in substrate ESI-MS analysis on solid and viscous samples.