Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which is a label-free imaging technique, determines the spatial distribution and relative abundance of versatile endogenous metabolites in tissues. Meanwhile, matrix selection is generally regarded as a pivotal step in MALDI tissue imaging. This study presents the first report of a novel MALDI matrix, 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine (HNTP), for the in situ detection and imaging of endogenous metabolites in rat liver and brain tissues by MALDI-MS in positive-ion mode. The HNTP matrix exhibits excellent characteristics, including strong ultraviolet absorption, μm-scale matrix crystals, high chemical stability, low background ion interference, and high metabolite ionization efficiency. Notably, the HNTP matrix also shows superior detection capabilities, successfully showing 185 detectable metabolites in rat liver tissue sections. This outperforms the commonly used matrices of 2,5-dihydroxybenzoic acid and 2-mercaptobenzothiazole, which detect 145 and 120 metabolites from the rat liver, respectively. Furthermore, a total of 152 metabolites are effectively detected and imaged in rat brain tissue using the HNTP matrix, and the spatial distribution of these compounds clearly shows the heterogeneity of the rat brain. The results demonstrate that HNTP is a new and powerful positive-ion mode matrix to enhance the analysis of metabolites in biological tissues by MALDI-MSI.

中文翻译：

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2-羟基-5-硝基-3-(三氟甲基)吡啶作为增强组织代谢物 MALDI 成像的新型基质

基质辅助激光解吸/电离质谱成像（MALDI-MSI）是一种无标记成像技术，可确定组织中多种内源代谢物的空间分布和相对丰度。同时，基质选择通常被认为是MALDI组织成像的关键步骤。本研究首次报告了一种新型 MALDI 基质 2-羟基-5-硝基-3-(三氟甲基)吡啶 (HNTP)，用于通过 MALDI-MS 对大鼠肝脏和脑组织中的内源代谢物进行原位检测和成像在正离子模式下。 HNTP基质表现出优异的特性，包括强紫外吸收、μm级基质晶体、高化学稳定性、低背景离子干扰和高代谢物电离效率。值得注意的是，HNTP 矩阵还显示出卓越的检测能力，成功显示了大鼠肝组织切片中的 185 种可检测代谢物。这优于常用的 2,5-二羟基苯甲酸和 2-巯基苯并噻唑基质，这两种基质分别可检测来自大鼠肝脏的 145 种和 120 种代谢物。此外，使用 HNTP 矩阵在大鼠脑组织中总共有效检测和成像了 152 种代谢物，这些化合物的空间分布清楚地显示了大鼠大脑的异质性。结果表明，HNTP 是一种新型强大的正离子模式基质，可增强 MALDI-MSI 对生物组织中代谢物的分析。