Mass Spectrometry Imaging in Drug Discovery and Better Therapeutic Design

Assessing the molecular component of biological samples in situ by mass spectrometry is a rapidly developing technique. During drug discovery and development, knowledge of spatial distribution of drug and metabolites within different organs are essential to better understand the DMPK and toxicity profile. Much of the recent advances in mass spectrometry imaging (MSI) techniques have been due to improvements with DESI (Desorption Electrospray) and MALDI (Matrix Assisted Laser Desorption) ionization modes, which enables the measurement of molecular distribution without having to use radio-labeled compounds unlike whole-body autoradiography. Other advantages of mass spectrometry imaging include the ability to map the tissue level distribution of parent compound as well as all metabolites. Furthermore, MSI experiments allow one to simultaneously capture the endogenous molecular signature of across the tissue (endogenous metabolites or lipid) and these biomarkers can be used as surrogate markers of toxicity or cellular response. This discussion will highlight the use of MSI in drug discovery and development as a useful tool that allow us to better understand drug and metabolite distribution, toxicity markers, and mechanism of action very early during the discovery process.