title: Quantification of small molecule drugs in biological tissue sections by imaging mass spectrometry using surrogate tissue-based calibration standards.
abstract: Quantitative analysis of administered drugs in biological tissues is essential for understanding the mechanisms underlying their efficacy or toxicity. Imaging mass spectrometry (IMS) may allow the quantification of targeted drugs in tissue sections along with the visualization of their spatial distribution. In this study, surrogate tissue-based calibration standards were prepared to quantify a small molecule drug (S-777469 or raclopride) in tissue sections of mice administered with the drug, followed by analysis with a linear ion trap mass spectrometer equipped with a matrix-assisted laser desorption/ionization (MALDI) source. The distribution of the drugs in the dissected organs was clearly visualized by MALDI-IMS. The drug concentration determined using the calibration standards prepared for MALDI-IMS analysis was highly consistent with that determined by liquid chromatography-tandem mass spectrometry, and the quantification in multiple organs was enabled. The results of this study show that MALDI-IMS can be used to quantify small molecule drugs in biological tissue sections using surrogate tissue-based calibration standards.
authors.affiliation: Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takai
authors.affiliation: Drug Developmental Research Laboratories, Shionogi & Co., Ltd.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
keywords: imaging mass spectrometry; matrix-assisted laser desorption/ionization; quantification
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