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Updated: Jun 1, 2025

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使用多模式质谱成像对药物诱导的肝损伤的调查

Bryn Flinders¹, Lennart Huizing¹, Bhanu Singh²

¹Maastricht MultiModal Molecular Imaging Institute (M4i), Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.

Journal of the American Society for Mass Spectrometry

|January 17, 2025

概括

矩阵辅助激光脱离电离质谱成像 (MALDI-MSI) 提供了对药物毒性的空间见解. 这种技术将药物分布和代谢物与组织学发现相关联,有助于临床前药物发现.

科学领域:

药理学药理学是指药理学的学科.
毒理学毒理学毒理学
分析化学分析化学

背景情况:

药物毒性是临床前药物开发失败的主要原因.
目前的方法如组织学和LC-MS缺乏空间分子信息.
矩阵辅助激光脱离电离质谱成像 (MALDI-MSI) 为同时检测提供了一种无标签的方法.

研究的目的:

为了证明MALDI-MSI在机械毒理学中的实用性.
为了将药物和代谢物分布与观察到的组织病变相关联.
为了可视化药物诱导的肝脏组织中的毒性,具有分子特异性.

主要方法:

使用MALDI-MSI对狗肝脏组织的分析.
同时检测B药物,其代谢物 (A和N氧化物) 和内源物种.
利用正负离子模式进行全面的组织分析.
与组织学检查相关联的质谱成像数据.

主要成果:

MALDI-MSI成功地绘制了B类药物及其代谢物在肝脏组织中的空间分布.
给狗服用A化合物的肝脏病变仅与原始化合物有关.
给狗服用B化合物的肝脏病变与原始化合物及其代谢物有关.
MALDI-MSI确定了内源性分子标记物,以精确可视化组织学损伤.

结论:

MALDI-MSI是药物开发中的机械毒理学研究的强大工具.
该技术使药物/代谢物分布与组织病理直接相关.
MALDI-MSI通过提供空间分子信息来增强对药物诱导毒性的理解.

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