Use of Matrix Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI-IMS) in the development of novel small molecule drugs

Modern drug research and development includes the study of drug distribution and its metabolites within the biological organ and tissues. The high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) is currently widely employed in the study of drug metabolism and pharmacokinetic characterization of new drug molecules. Today, the newest frontier, which adds the mass spectrometry to the arsenal of tools for the direct analysis of tissue biopsies and molecular diagnosis, is typically called Matrix Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI-IMS). This powerful analytical tool is a new molecular imaging technique which in essence takes a mass spectral snapshots of intact tissue sections, revealing how the macromolecules, such as peptides and protein, and small molecular drugs and their metabolites are spatially distributed within a given biological tissue sample. In this chapter, MALDI-IMS technology is presented as well as applications of such technology in drug development and in clinical pharmacology. It provides direct, unambiguous evidence for the presence of drug substance in tissue sections.