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开发高透量定量成像质谱仪,用于分析组织中药物分布

Yukari Tanaka¹

¹Drug Metabolism and Pharmacokinetics and Analytical Sciences, Laboratory for Drug Discovery and Development, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.

Journal of mass spectrometry : JMS

|April 8, 2025

概括

一种新的高通量定量MALDI-IMS方法有效地测量了药物透到大脑转移中的程度. 该技术支持早期药物发现,通过快速查和理解药物药理动力学.

科学领域:

药理学药理学是指药理学的学科.
分析化学分析化学
生物技术是生物技术.

背景情况:

矩阵辅助激光脱吸/电离成像质谱 (MALDI-IMS) 对药物发现和开发至关重要.
评估药物透到大脑转移的情况对于治疗疗效至关重要.

研究的目的:

开发一种高通量定量MALDI-IMS方法来比较epertinib和lapatinib的大脑透率.
在HER2阳性乳腺癌和T790M-EGFR阳性肺癌的静脉内注射小鼠模型 (IVM) 中评估epertinib对lapatinib的疗效.

主要方法:

开发了一种使用简单的校准曲线而没有空白组织的定量MALDI-IMS方法.
使用带有MALDI离子源的线性离子陷质谱仪分析脑部部分和校准曲线.
通过液体染色学-并联质谱法 (LC-MS/MS) 验证的结果.

主要成果:

定量MALDI-IMS方法表明,对于epertinib和lapatinib,具有强烈的线性,广泛的动态范围和低变化 (RSD<20%).
埃珀提尼布和拉帕提尼布有效地从乳腺癌IVMs中的大脑部分提取出来.
在肺癌IVM中对epertinib的定量MALDI-IMS结果与LC-MS/MS测量有很好的相关性.

结论:

高通量定量MALDI-IMS是一种可重复和高效的工具,用于早期候选药物选择.
这种方法有助于快速选,了解药物的疗效,毒性和药理动力学/药理动力学.
这项研究支持epertinib在特定大脑转移模型中比lapatinib更有潜力.

关键词:

马尔迪马尔迪马尔迪埃珀蒂尼布 (epertinib) 是一种药物.具有高通量功率的高通量功率.拉帕提尼布 (lapatinib) 是一种治疗方法.量化成像质谱学质谱学

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