ポスター発表
- 第2日 5月16日（水） ポスター会場
-
2P-28 PDF
Multiplex Molecular Imaging of Drugs and Metabolites in Dosed Tissues by DESI Mass Spectrometry
Introduction
Liquid chromatography (LC) based assays are gold standards for determining the concentrations of drugs/metabolites in plasma during the drug discovery process. However, drug candidates often have different effects on various target tissues and there is an asymmetrical relationship between the concentrations of drugs and metabolites in the plasma versus the targeted tissues. Whole-body autoradiography has been utilized to determine the distribution of radiolabeled drugs and their metabolite candidates in preclinical animal models. Mass spectrometry imaging (MSI) offers a possibility of mapping several drug molecules without isotope labeling. Here we showcase the utility of DESI MSI to assess simultaneous detection of drug and metabolites.
Method
One cohort of mice were orally administered with terfenadine, olanzapine, moxifloxacin and erlotinib at pharmacologically relevant levels of 25, 10, 10 and 25 mg/kg, respectively. A second cohort was dosed with vehicle to act as a control. Liver sections were taken from each cohort at 2 and 6 hours post administration from the euthanized animals. DESI MSI analysis was performed on a quadruple time of flight (Xevo G2-XS Q-Tof, Waters Corporations). High Definition Imaging (HDI) version 1.4 software was used to define DESI imaging experiments, as well as, process and visualize the collected ion images.