A strategy based on postcolumn electrophoretic mobility control (EMC) was developed to alleviate the adverse effects of ion pairing reagents and/or nonvolatile buffers on liquid chromatography-mass spectrometry (LC/MS).The device created to achieve this goal consisted of a poly(dimethylsiloxane) (PDMS)-based junction reservoir, a short connecting capillary, and an electrospray ionization (ESI) sprayer connected to the outlet of the high-performance liquid chromatography (HPLC) column.By apply different voltages to the junction reservoir and the ESI emitter, an electric field was created across the connecting capillary.Due to the electric field, positively charged and neutral analytes migrated toward the ESI sprayer, whereas the negative charged additives remained in the junction reservoir and were removed from the ionization process.This approach has been successfully demonstrated on peptides analysis in LC/ESI-MS with trifluoroacetic acid (TFA)-containing mobile phase.