Targeted desorption electrospray ionization mass spectrometry imaging for drug distribution, toxicity, and tissue classification studies

Dannhorn, A. et al. (2023) Targeted desorption electrospray ionization mass spectrometry imaging for drug distribution, toxicity, and tissue classification studies. Metabolites, 13(3), 377. (doi: 10.3390/metabo13030377) (PMID:36984817) (PMCID:PMC10060000)

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With increased use of mass spectrometry imaging (MSI) in support of pharmaceutical research and development, there are opportunities to develop analytical pipelines that incorporate exploratory high-performance analysis with higher capacity and faster targeted MSI. Therefore, to enable faster MSI data acquisition we present analyte-targeted desorption electrospray ionization–mass spectrometry imaging (DESI-MSI) utilizing a triple-quadrupole (TQ) mass analyzer. The evaluated platform configuration provided superior sensitivity compared to a conventional time-of-flight (TOF) mass analyzer and thus holds the potential to generate data applicable to pharmaceutical research and development. The platform was successfully operated with sampling rates up to 10 scans/s, comparing positively to the 1 scan/s commonly used on comparable DESI-TOF setups. The higher scan rate enabled investigation of the desorption/ionization processes of endogenous lipid species such as phosphatidylcholines and a co-administered cassette of four orally dosed drugs—erlotininb, moxifloxacin, olanzapine, and terfenadine. This was used to enable understanding of the impact of the desorption/ionization processes in order to optimize the operational parameters, resulting in improved compound coverage for olanzapine and the main olanzapine metabolite, hydroxy-olanzapine, in brain tissue sections compared to DESI-TOF analysis or matrix-assisted laser desorption/ionization (MALDI) platforms. The approach allowed reducing the amount of recorded information, thus reducing the size of datasets from up to 150 GB per experiment down to several hundred MB. The improved performance was demonstrated in case studies investigating the suitability of this approach for mapping drug distribution, spatially resolved profiling of drug-induced nephrotoxicity, and molecular–histological tissue classification of ovarian tumors specimens.

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” (Grant agreement ID: 617896) for supporting the research.
Glasgow Author(s) Enlighten ID:Goodwin, Dr Richard
Authors: Dannhorn, A., Doria, M. L., McKenzie, J., Inglese, P., Swales, J. G., Hamm, G., Strittmatter, N., Maglennon, G., Ghaem-Maghami, S., Goodwin, R. J.A., and Takats, Z.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Metabolites
ISSN (Online):2218-1989
Published Online:03 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Metabolites 13(3): 377
Publisher Policy:Reproduced under a Creative Commons License

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