Accurate Mass Drug Imaging for Metabolite Distribution: Extra Information with Little Extra Effort

摘要

A single, label-free, high resolution imaging MALDI MS experiment was capable of detecting the distribution of Genentech compound X and its metabolites in whole body with high mass accuracy and no need for a priori metabolite knowledge. Endogenous components such as peptides, phospholipids and heme can also be extracted from a single imaging experiment: (1) For example, lipid distribution may provide insight into membrane compositions of brain and tumor which can influence drug permeability at these sites. Imaging MALDI MS experiments can guide early drug discovery efforts and has been successfully applied to whole-body samples to reveal the disposition of new chemical entities, perhaps affording valuable information to support go/no go decisions: (1) Identify potential on-target efficacy and off-target liabilities/toxicity; (2) Identify routes of clearance; (3) Early complement to WBA studies.