Takai Nozomi, Tanaka Yukari, Saji Hideo
Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd.
Drug Developmental Research Laboratories, Shionogi & Co., Ltd.
Mass Spectrom (Tokyo). 2014;3(1):A0025. doi: 10.5702/massspectrometry.A0025. Epub 2014 Feb 1.
Quantitative analysis of administered drugs in biological tissues is essential for understanding the mechanisms underlying their efficacy or toxicity. Imaging mass spectrometry (IMS) may allow the quantification of targeted drugs in tissue sections along with the visualization of their spatial distribution. In this study, surrogate tissue-based calibration standards were prepared to quantify a small molecule drug (S-777469 or raclopride) in tissue sections of mice administered with the drug, followed by analysis with a linear ion trap mass spectrometer equipped with a matrix-assisted laser desorption/ionization (MALDI) source. The distribution of the drugs in the dissected organs was clearly visualized by MALDI-IMS. The drug concentration determined using the calibration standards prepared for MALDI-IMS analysis was highly consistent with that determined by liquid chromatography-tandem mass spectrometry, and the quantification in multiple organs was enabled. The results of this study show that MALDI-IMS can be used to quantify small molecule drugs in biological tissue sections using surrogate tissue-based calibration standards.
对生物组织中施用药物进行定量分析对于理解其疗效或毒性背后的机制至关重要。成像质谱（IMS）可以对组织切片中的靶向药物进行定量，并可视化其空间分布。在本研究中，制备了基于替代组织的校准标准品，以对给药小鼠的组织切片中的小分子药物（S-777469或雷氯必利）进行定量，随后使用配备基质辅助激光解吸/电离（MALDI）源的线性离子阱质谱仪进行分析。通过MALDI-IMS可以清晰地观察到药物在解剖器官中的分布。使用为MALDI-IMS分析制备的校准标准品测定的药物浓度与液相色谱-串联质谱法测定的浓度高度一致，并且能够对多个器官进行定量。本研究结果表明，MALDI-IMS可用于使用基于替代组织的校准标准品对生物组织切片中的小分子药物进行定量。
