Salt Tolerance Enhancement of Liquid Chromatography-Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Using Matrix Additive Methylenediphosphonic Acid

Abstract

Mass spectrometry (MS) is a highly sensitive analytical technique that is ooen coupled with liquid chromatography (LC). However, some buuering salts used in LC (e.g., phosphate and tris(hydroxymethyl) aminomethane (Tris)) are incompatible with MS since they cause ion-source contamination and signal suppression. In this study, we examined salt tolerance of MALDI and applied a matrix additive methylene-diphosphonic acid (MDPNA) to reduce salt-induced signal suppression. MDPNA signiicantly improved the salt tolerance of MALDI-MS. Using ammonium formate buuer at pH 5.0, the eeective range of buuer-ing salt concentration in MALDI-MS using MDPNA was estimated up to 250 mM. MDPNA reduced signal suppression caused by buuering salts at pH 4.0 to 8.0. We observed that MDPNA eeectively worked over a wide range of buuer conditions. MDPNA was further applied to hydrophilic interaction chromatography (HILIC) and chromatofocusing-MALDI-MS. As a result, the analytes in the eluent containing high-concentration salts were detected with high sensitivity. us, our study provides simple and fast LC-MALDI-MS analysis technique not having strict limitation of buuering condition in LC by using matrix additive MDPNA.