Novel mimetic tissue standards for precise quantitative mass spectrometry imaging of drug and neurotransmitter concentrations in rat brain tissues.

IF 3.8 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Analytical and Bioanalytical Chemistry Pub Date : 2024-11-01 Epub Date: 2024-08-10 DOI:10.1007/s00216-024-05477-5
Kenichi Watanabe, Sayo Takayama, Toichiro Yamada, Masayo Hashimoto, Jun Tadano, Tetsuya Nakagawa, Takao Watanabe, Eiichiro Fukusaki, Izuru Miyawaki, Shuichi Shimma
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引用次数: 0

Abstract

Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI.

Abstract Image

用于大鼠脑组织中药物和神经递质浓度精确定量质谱成像的新型模拟组织标准。
了解药物浓度与其疗效或副作用之间的关系对药物开发至关重要,尤其是了解中枢神经系统药物的疗效,量化药物诱导的神经递质等内源性代谢物水平的特定部位变化。近来,利用基质辅助激光解吸/电离(MALDI)-质谱成像(MSI)评估药物和内源性代谢物的定量分布在药物发现研究中备受关注。然而,MALDI-MSI 定量(定量质谱成像,QMSI)是一项新兴技术,在药物发现研究中的实用性和便利性有待进一步开发。本研究开发了一种可靠的 QMSI 方法,利用 MALDI-MSI 定量大鼠脑中的氯氮平(抗精神病药物)和多巴胺及其代谢物。作为一种替代方法,我们使用粉末状冷冻组织建立了一种改进的 QMSI 模拟组织模型,从而能够准确定量大鼠大脑中的氯氮平水平。此外,我们还用改进后的方法评估了药物引起的多巴胺及其代谢物浓度波动。该方法可定量评估药物在大脑中的定位以及药物诱导的内源性代谢物浓度变化,证明了 QMSI 的实用性。
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来源期刊
CiteScore
8.00
自引率
4.70%
发文量
638
审稿时长
2.1 months
期刊介绍: Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.
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