Matrix‐assisted laser desorption/ionization mass spectrometry with additives to 2,5‐dihydroxybenzoic acid

Selected benzoic acid derivatives and related substances were used as additives to 2,5‐dihydroxybenzoic acid (2,5DHB) and the performance of the mixtures in matrix‐assisted laser desorption/ionization mass spectrometry was investigated. Using benzoic acid derivatives substituted at position 2 and/or 5 or related substances as a co‐matrix in the 1–10% range with 2,5DHB results in improved ion yields and signal‐to‐noise ratio of analyte molecules, especially for the high‐mass range. The enhanced performance is prominent for 2‐hydroxy‐5‐methoxybenzoic acid and exists for both proteins and oligosaccharides. It is suggested that the improvement is caused by a disorder in the 2,5DHB crystal lattice allowing ‘softer’ desorption. Charge transfer from matrix ions to additive molecules at the expense of analyte ionization gives a simple explanation for the deteriorating effects of some tested additives.