Abstract Detailed knowledge on the spatiotemporal distribution of drugs or drug candidates in bio-tissues is of vital importance for the determination of their underlying mechanisms of action as well as evaluation of potential side effects. The present work involved the establishment of a matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) method for the visualization of distribution of salidroside, a bioactive ingredient of Rhodiola L. Crassulaceae, in multiple mouse tissue sections. 1,5-Diaminonaphthalene (1,5-DAN) hydrochloride was selected as the most suitable matrix by comparing the signal intensity produced by MALDI-MS analysis following cocrystallization of salidroside with different matrix candidates. The matrix deposition procedure was systematically optimized to obtain the best sensitivity as well as homogeneous matrix coverage on the tissue sections. The measurements were carried out in the negative reflectron ion mode (m/z 300–350 Da) with a spatial resolution of 200 μm. The proposed method demonstrated good performance with respect to specificity, linearity, and sensitivity, and the method exhibited a relatively reasonable run time. The approach was applied to determine the temporal-spatial location of salidroside in the kidney, liver, spleen, heart, lung, and brain following intravenous administration of the drug in mice. The results indicate that salidroside exhibited a heterogeneous distribution in the kidney and heart, and it can be rapidly eliminated by kidney 5 min after administration. The distribution information obtained by the in situ and label-free imaging technique proposed herein may benefit to our understanding of the activities and potential transient toxicities of salidroside in various organs.

中文翻译：

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通过 MALDI-MS 成像原位无标记可视化红景天苷在多个小鼠器官中的组织分布

摘要 详细了解生物组织中药物或候选药物的时空分布对于确定其潜在作用机制以及评估潜在副作用至关重要。目前的工作涉及建立基质辅助激光解吸电离质谱成像 (MALDI-MSI) 方法，用于可视化红景天科景天科生物活性成分红景天苷在多个小鼠组织切片中的分布。通过比较红景天苷与不同基质候选物共结晶后 MALDI-MS 分析产生的信号强度，选择 1,5-二氨基萘 (1,5-DAN) 盐酸盐作为最合适的基质。基质沉积过程被系统地优化以获得最佳灵敏度以及组织切片上的均匀基质覆盖。测量在负反射离子模式（m/z 300-350 Da）下进行，空间分辨率为 200 μm。所提出的方法在特异性、线性和灵敏度方面表现出良好的性能，并且该方法表现出相对合理的运行时间。该方法用于确定红景天苷在小鼠静脉内给药后肾脏、肝脏、脾脏、心脏、肺和大脑中的时空位置。结果表明，红景天苷在肾脏和心脏中分布不均，给药后5分钟即可被肾脏迅速清除。