An experimental comparison of electrospray ion‐trap and matrix‐assisted laser desorption/ionization post‐source decay mass spectra for the characterization of small drug molecules

An experimental comparison of product ion spectra produced by matrix-assisted laser desorption/ionization (MALDI) and electrospray ion-trap MS( n) for a group of small drug molecules is presented in this paper. The goal of the study was to demonstrate the usefulness of MALDI-MS with post-source decay (PSD) and collision-induced dissociation (CID) for the structural analysis of small drug molecules in the drug discovery process, where traditionally electrospray LC/MS methods are used. PSD and PSD/CID gave diverse product ions that were highly indicative of the structure of the drugs investigated (a group of 4-quinolone antibiotics and oleandomycin). In addition, the number of different product ions generated with MALDI-MS was always higher than with electrospray ion-trap MS( n) (with n < or =4) for the drug molecules studied. This investigation also showed that the choice of a suitable MALDI matrix for the analysis of low molecular weight compounds is quite important. It was found that of the three matrices examined, alpha-cyano-4-hydroxycinnamic acid (alpha-CHCA) produced the most intense fragmentation levels while TiO2, with its advantage of virtually no low mass background signals, did not generate quite the same amount of information.