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 MSn 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 (with n less than or equal to4) 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. Copyright (C) 2001 John Wiley & Sons, Ltd.