Guo Runcong, Zhou Lei, Chen Xiaoyan
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501 Haike Road, Shanghai, 201203, People's Republic of China.
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, People's Republic of China.
Anal Bioanal Chem. 2021 Sep;413(23):5835-5847. doi: 10.1007/s00216-021-03563-6. Epub 2021 Aug 18.
Fluoropezil (DC20) is a new selective acetylcholinesterase inhibitor, and it was developed for the treatment of Alzheimer's disease patients. In this study, a desorption electrospray ionization source coupling ion mobility mass spectrometry imaging (DESI/IMS-MSI) method was developed to explore the distribution of DC20 in brain tissue following oral administration. Rat brain coronal slices obtained 1 h and 3 h following drug dosing were used in the study. D6-DC20 was used as internal standard and sprayed by matrix sprayer on the brain slices to calibrate the matrix effect. Ion mobility separation was used to reduce the interference from background noise and the biological matrix. By optimizing DESI-MSI parameters for improved sensitivity, the limit of quantitation of the method was 1.45 pg/mm with a linear range from 1.45 to 72.7 pg/mm. DESI-MSI data showed that DC20 could quickly enter and diffuse across whole brain and tended to be much more enriched in striatum than cerebral cortex and hippocampus, which was consistent with quantitative analysis using high-performance liquid chromatography-electrospray tandem mass spectrometry to measure DC20 concentration in each homogenized brain sub-region. The workflow of tissue imaging method optimization and strategy were established, and for the first time, the DESI-MSI technique and optimized method were used to explore the distribution characteristics of DC20 in rat brain, which could help elucidate pharmacological effect mechanisms and improve clinical outcomes.
氟哌齐尔（DC20）是一种新型选择性乙酰胆碱酯酶抑制剂，研发用于治疗阿尔茨海默病患者。在本研究中，开发了一种解吸电喷雾电离源耦合离子淌度质谱成像（DESI/IMS-MSI）方法，以探究口服给药后DC20在脑组织中的分布。研究使用给药后1小时和3小时获取的大鼠脑冠状切片。D6-DC20用作内标，通过基质喷雾器喷在脑切片上以校准基质效应。采用离子淌度分离减少背景噪声和生物基质的干扰。通过优化DESI-MSI参数提高灵敏度，该方法的定量限为1.45 pg/mm，线性范围为1.45至72.7 pg/mm。DESI-MSI数据表明，DC20可快速进入并扩散至全脑，且在纹状体中的富集程度远高于大脑皮层和海马体，这与使用高效液相色谱-电喷雾串联质谱法测量各匀浆脑亚区中DC20浓度的定量分析结果一致。建立了组织成像方法优化的工作流程和策略，首次运用DESI-MSI技术及优化方法探究DC20在大鼠脑中的分布特征，这有助于阐明药理作用机制并改善临床疗效。
