Spatial Analysis of Drug Absorption, Distribution, Metabolism, and Toxicology Using Mass Spectrometry Imaging

Authors

Michelle L Spruill
Mirjana Maletic-Savatic
Howard Martin
Feng Li
Xinli Liu

Publication Date

7-1-2022

Journal

Biochemical Pharmacology

DOI

10.1016/j.bcp.2022.115080

PMID

35561842

PMCID

PMC9744413

PubMedCentral® Posted Date

12-12-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Kidney, Liver, Lung, Mass Spectrometry, Spatial Analysis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Mass spectrometry imaging, MSI, Drug absorption, Drug distribution, Xenobiotic metabolism, Pharmacokinetics, Toxicology

Abstract

Mass spectrometry imaging (MSI) is emerging as a powerful analytical tool for detection, quantification, and simultaneous spatial molecular imaging of endogenous and exogenous molecules via in situ mass spectrometry analysis of thin tissue sections without the requirement of chemical labeling. The MSI generates chemically specific and spatially resolved ion distribution information for administered drugs and metabolites, which allows numerous applications for studies involving various stages of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). MSI-based pharmacokinetic imaging analysis provides a histological context and cellular environment regarding dynamic drug distribution and metabolism processes, and facilitates the understanding of the spatial pharmacokinetics and pharmacodynamic properties of drugs. Herein, we discuss the MSI's current technological developments that offer qualitative, quantitative, and spatial location information of small molecule drugs, antibody, and oligonucleotides macromolecule drugs, and their metabolites in preclinical and clinical tissue specimens. We highlight the macro and micro drug-distribution in the whole-body, brain, lung, liver, kidney, stomach, intestine tissue sections, organoids, and the latest applications of MSI in pharmaceutical ADMET studies.