Application of AP-MALDI Imaging Mass Microscope for the Rapid Mapping of Imipramine, Chloroquine, and Their Metabolites in the Kidney and Brain of Wild-Type Mice.

Ariful Islam, Takumi Sakamoto, Qing Zhai, Md Muedur Rahman, Md Al Mamun, Yutaka Takahashi, Tomoaki Kahyo, Mitsutoshi Setou
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引用次数: 5

Abstract

Mass spectrometry imaging (MSI) is well-known for the non-labeling visualization of analytes, including drugs and their metabolites in biological samples. In this study, we applied three different tools of MSI, desorption electrospray ionization (DESI)-MSI, matrix-assisted laser desorption ionization (MALDI)-MSI, and a newly developed atmospheric pressure (AP)-MALDI-MSI known as iMScopeTM QT for rapid mapping of imipramine, chloroquine, and their metabolites in C57BL/6 male wild-type mice. Among three MSI tools, better detection capability for targeted drugs at higher speed (up to 32 pixels/s) was observed in iMScope QT. It revealed that imipramine and its metabolites were significantly accumulated in the renal cortex of mice, but chloroquine and its metabolites were highly accumulated in the renal pelvis and renal medulla of mice. Additionally, a higher accumulation of imipramine was noted in the thalamus, hypothalamus, septum, and hindbrain of mice brains. However, chloroquine and its metabolites showed notable accumulation in the lateral ventricle, fourth ventricle, and fornix of the mice brains. These findings of our study can be helpful in understanding clinically relevant properties, efficacy, and potential side effects of these drugs. Our study also showed the potentiality of iMScope QT for rapid mapping of small drugs and their metabolites in biological samples.

Abstract Image

Abstract Image

Abstract Image

应用AP-MALDI成像质粒显微镜快速定位野生型小鼠肾和脑中丙咪嗪、氯喹及其代谢物
质谱成像(MSI)以非标记可视化分析物而闻名,包括生物样品中的药物及其代谢物。在这项研究中,我们应用了三种不同的MSI工具,解吸电喷雾电离(DESI)-MSI,基质辅助激光解吸电离(MALDI)-MSI,以及新开发的大气压(AP)-MALDI-MSI,即iMScopeTM QT,用于C57BL/6雄性野生型小鼠丙咪嗪,氯喹及其代谢物的快速定位。在3种MSI工具中,iMScope QT对靶向药物的检测速度更快(可达32像素/秒),显示丙咪嗪及其代谢物在小鼠肾皮质中有显著的积累,而氯喹及其代谢物在小鼠肾盂和肾髓质中有较高的积累。此外,在小鼠大脑的丘脑、下丘脑、隔膜和后脑中发现了较高的丙咪嗪积累。然而,氯喹及其代谢物在小鼠的侧脑室、第四脑室和穹窿中有明显的蓄积。我们的研究结果有助于了解这些药物的临床相关特性、疗效和潜在的副作用。我们的研究还显示了iMScope QT在生物样品中快速定位小药物及其代谢物的潜力。
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