Correlating mass spectrometry imaging and liquid chromatography-tandem mass spectrometry for tissue-based pharmacokinetic studies

Dannhorn, A., Kazanc, E., Hamm, G., Swales, J. G., Strittmatter, N., Maglennon, G., Goodwin, R. J.A. and Takats, Z. (2022) Correlating mass spectrometry imaging and liquid chromatography-tandem mass spectrometry for tissue-based pharmacokinetic studies. Metabolites, 12(3), 261. (doi: 10.3390/metabo12030261) (PMID:35323705) (PMCID:PMC8954739)

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Abstract

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a standard tool used for absolute quantification of drugs in pharmacokinetic (PK) studies. However, all spatial information is lost during the extraction and elucidation of a drugs biodistribution within the tissue is impossible. In the study presented here we used a sample embedding protocol optimized for mass spectrometry imaging (MSI) to prepare up to 15 rat intestine specimens at once. Desorption electrospray ionization (DESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) were employed to determine the distributions and relative abundances of four benchmarking compounds in the intestinal segments. High resolution MALDI-MSI experiments performed at 10 µm spatial resolution allowed to determine the drug distribution in the different intestinal histological compartments to determine the absorbed and tissue bound fractions of the drugs. The low tissue bound drug fractions, which were determined to account for 56−66% of the total drug, highlight the importance to understand the spatial distribution of drugs within the histological compartments of a given tissue to rationalize concentration differences found in PK studies. The mean drug abundances of four benchmark compounds determined by MSI were correlated with the absolute drug concentrations. Linear regression resulted in coefficients of determination (R2) ranging from 0.532 to 0.926 for MALDI-MSI and R2 values ranging from 0.585 to 0.945 for DESI-MSI, validating a quantitative relation of the imaging data. The good correlation of the absolute tissue concentrations of the benchmark compounds and the MSI data provides a bases for relative quantification of compounds within and between tissues, without normalization to an isotopically labelled standard, provided that the compared tissues have inherently similar ion suppression effects.

Item Type:Articles
Additional Information:The authors would like to thank the Biotechnology and Biological Sciences Research Council (BBSRC) for the case funding for A.D. [BB/N504038/1] and European Research Council Consolidator Grant “MASSLIP” for supporting the research.
Keywords:DESI, MALDI, mass spectrometry imaging, DMPK, drug absorption, tissue imaging.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Goodwin, Dr Richard
Creator Roles:
Goodwin, R. J.A.Conceptualization, Funding acquisition, Resources, Supervision, Writing – review and editing
Authors: Dannhorn, A., Kazanc, E., Hamm, G., Swales, J. G., Strittmatter, N., Maglennon, G., Goodwin, R. J.A., and Takats, Z.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Metabolites
Publisher:MDPI
ISSN:2218-1989
ISSN (Online):2218-1989
Published Online:18 March 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Metabolites 12(3): 261
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.14469/hpc/10255

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