Tissue Distribution of Compound X and its Metabolites in Jck Mouse Polycystic Kidneys Using Mass Spectrometry Imaging (MSI)

摘要

Compound X was detected in the kidneys from compound X dosed animals but not from vehicle dosed animals. From imaging analysis at spatial resolution of 120 μm, compound X, M18, M19 and M29 were detected in the kidney from the compound X dosed animals but not M25 due to tissue interferences. Among dosed animals, imaging MS of kidneys showed high variability of compound X, consistent with the total exposure of compound X determined by LC-MS/MS. From imaging analysis at spatial resolution at 30 μm, M18 and M19 seemed to be distributed broadly across different cells/regions than parent and M29. Co-localization was found between the drug and its M29 metabolite followed by M18 and M19, consistent with the extent of metabolic modification of these three metabolites.