Coating of a MALDI target with metal oxide nanoparticles by droplet-free electrospraying – A versatile tool for in situ enrichment of human globin adducts of halogen-containing drug metabolites

Abstract

The strategies for integration of different orthogonal analytical procedures directly on the targets for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) are being intensively developed over the last two decades. This methodology, which is usually referred to as “lab-on-a-plate”, proved to be the method of choice for fast and reproducible sample preparation prior to MALDI-MS analysis. To date, numerous “lab-on-a-plate” protocols for enrichment of phosphorylated peptides by metal oxide affinity chromatography (MOAC) are established. However, despite this, a straightforward and efficient implementation of the on-target workflow for selective MOAC-based enrichment of the protein adducts formed by halogen-containing xenobiotics is still missing. Therefore, here we present a successful application of droplet-free electrospraying under normal conditions for efficient deposition of metal oxide (MeOx) nanoparticles on the MALDI target. Here we employed oxides of four transition metals – Fe(III), Co(II/III), Ni(II) and Cu(II). These materials were synthesized by the microwave-assisted sol–gel approach and electrosprayed post-synthetically on a stainless steel MALDI target. Thus, stable coating of the target could be achieved without heating and any damage of its surface. As a case study, MALDI targets were deposited with MeOx nanoparticles, and human globin adducts with in vitro generated diclofenac (DCL) metabolites were enriched on spot from the tryptic digests of the protein treated with DCL oxidation mixture. This extraction procedure gave access to efficient, selective and reliable identification of the human globin adduct with decarboxylation oxidation product of DCL. The developed approach appears to be promising for in situ enrichment of halogen-containing adducts of proteins due to simplifying the sample treatment and minimizing sample losses.