TY - JOUR

T1 - Mass spectrometry imaging in drug distribution and drug metabolism studies

T2 - Principles, applications and perspectives

AU - Granborg, Jonatan Riber

AU - Handler, Anne Mette

AU - Janfelt, Christian

N1 - Funding Information: This work is partly funded by the Innovation Fund Denmark under File No. 7038-00017B and 8053-00212B . Publisher Copyright: © 2021 The Author(s)

PY - 2022

Y1 - 2022

N2 - New mass spectrometry imaging (MSI) techniques are gaining importance in various stages of the drug discovery and development chain as well as in more fundamental studies of drug delivery. The advantage of MSI is that for an imaging technique, the selectivity is very high and as a label-free technique, it enables simultaneous and compound-specific imaging of drugs and their metabolites. In addition to that, a vast number of endogenous metabolites, which may serve as tissue biomarkers, can be imaged simultaneously, providing a very extensive characterization of the sample. The present review focusses on the application of MSI for imaging of drugs and their metabolites, primarily is studies of drug distribution and drug metabolism. The first half provides a quite general introduction to MSI with the main focus on MALDI-MSI and DESI-MSI, which are the two most commonly applied MSI techniques for pharmaceutical applications. It also has sections where the necessary sample preparation, including cryo-sectioning, is discussed, along with sections on data analysis and quantitative MSI, which in particular for pharmaceutical applications plays an increasingly significant role. The second half of the paper presents examples of pharmaceutical applications of MSI. The chapter does not contain an exhaustive list of all published studies, but should be considered a curated list of examples where MSI has contributed with information which cannot readily be obtained by conventional analytical techniques. The examples are chosen to represent diverse fields within drug delivery (local and systemic) and drug metabolism with examples from different organs and from whole-body studies. The final section presents a broader look at ongoing trends within MSI and some thoughts on where MSI is heading in the years to come.

AB - New mass spectrometry imaging (MSI) techniques are gaining importance in various stages of the drug discovery and development chain as well as in more fundamental studies of drug delivery. The advantage of MSI is that for an imaging technique, the selectivity is very high and as a label-free technique, it enables simultaneous and compound-specific imaging of drugs and their metabolites. In addition to that, a vast number of endogenous metabolites, which may serve as tissue biomarkers, can be imaged simultaneously, providing a very extensive characterization of the sample. The present review focusses on the application of MSI for imaging of drugs and their metabolites, primarily is studies of drug distribution and drug metabolism. The first half provides a quite general introduction to MSI with the main focus on MALDI-MSI and DESI-MSI, which are the two most commonly applied MSI techniques for pharmaceutical applications. It also has sections where the necessary sample preparation, including cryo-sectioning, is discussed, along with sections on data analysis and quantitative MSI, which in particular for pharmaceutical applications plays an increasingly significant role. The second half of the paper presents examples of pharmaceutical applications of MSI. The chapter does not contain an exhaustive list of all published studies, but should be considered a curated list of examples where MSI has contributed with information which cannot readily be obtained by conventional analytical techniques. The examples are chosen to represent diverse fields within drug delivery (local and systemic) and drug metabolism with examples from different organs and from whole-body studies. The final section presents a broader look at ongoing trends within MSI and some thoughts on where MSI is heading in the years to come.

KW - Drug distribution

KW - Drug metabolism

KW - Mass spectrometry

KW - Mass spectrometry imaging

KW - PK

KW - Tissue analysis

U2 - 10.1016/j.trac.2021.116482

DO - 10.1016/j.trac.2021.116482

M3 - Review

AN - SCOPUS:85121240515

VL - 146

JO - Trends in Analytical Chemistry

JF - Trends in Analytical Chemistry

SN - 0165-9936

M1 - 116482

ER -