Applications of MALDI mass spectrometry imaging for pharmacokinetic studies during drug development.

Autor: Nishidate M; Clinical Pharmacology Dept., Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura-shi, Kanagawa, 247-8530, Japan., Hayashi M; Division of Molecular Pharmacology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan., Aikawa H; Division of Molecular Pharmacology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan., Tanaka K; DMPK Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda-shi, Saitama, 335-8505, Japan., Nakada N; Analysis & Pharmacokinetics Research Labs., Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka Tsukuba-shi, Ibaraki, 305-8585, Japan., Miura SI; External Affairs Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi-honcho, Chuo-ku, Tokyo, 103-8426, Japan., Ryu S; Division of Molecular Pharmacology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan., Higashi T; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan., Ikarashi Y; Office of New Drug V, Pharmaceuticals and Medical Devices Agency, 3-2-2, Kasumigaseki, Chiyoda-ku, Tokyo, 100-0013, Japan., Fujiwara Y; Strategic Planning Bureau, National, Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan., Hamada A; Division of Molecular Pharmacology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Department of Pharmacology and Therapeutics, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: akhamad@ncc.go.jp.
Jazyk: angličtina
Zdroj: Drug metabolism and pharmacokinetics [Drug Metab Pharmacokinet] 2019 Aug; Vol. 34 (4), pp. 209-216. Date of Electronic Publication: 2019 Apr 24.
DOI: 10.1016/j.dmpk.2019.04.006
Abstrakt: The concentration and distribution of a drug or its metabolites in tissues are key factors for understanding drug efficacy or toxicity. Conventional pharmacokinetic studies show that the plasma concentration of a drug is often unrelated to the intra-tissue concentration. Moreover, it is difficult to predict the distribution of a drug in tissues, particularly those with complex structures, even though the overall tissue concentration is measured by using homogenizing procedures. Mass spectrometry imaging (MSI) enables visualization of the spatial distribution and quantities of drugs in tissue sections without labeling, which can significantly impact on the development of new drugs and translational research. Recent advances in instrument technology and the knowledge accumulated to date could further improve the sensitivity, spatial resolution, and reproducibility of MSI. Here we present current applications of matrix-assisted laser desorption/ionization (MALDI)-MSI in pharmacokinetic imaging (PK-imaging) studies, give an overview of MALDI-MSI procedures, highlight the importance of internal standards, and give details of quantitative approaches. We also point out the need for standardizing MALDI-MSI techniques. PK-imaging using standardized MALDI-MSI methods, independent of instrument or technician expertise, is expected to contribute to acquiring reliable data in drug development and translational research in the future.
(Copyright © 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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