Unraveling the drug distribution in brain enabled by MALDI MS imaging with laser-assisted chemical transfer

作     者：Shuai Guo Kening Li Yanwen Chen Bin Li 

作者机构：State Key Laboratory of Natural Medicines and School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第4期

页      面：2120-2126页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070302[理学-分析化学] 0703[理学-化学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.81973703 and 81803957) the Natural Science Foundation of Jiangsu Province(No.BK20180567,China) 

主　　题：Pharmaceutical analysis Laser-assisted chemical transfer Mass spectrometry imaging Drug distribution Brain penetration 

摘      要：Accurate localization of central nervous system(CNS)drug distribution in the brain is quite challenging to matrix-assisted laser desorption/ionization(MALDI)mass spectrometry imaging(MSI),owing to the ionization competition/suppression of highly abundant endogenous biomolecules and MALDI ***,we developed a highly efficient sample preparation technique,laser-assisted chemical transfer(LACT),to enhance the detection sensitivity of CNS drugs in brain tissues.A focused diode laser source transilluminated the tissue slide coated with α-cyano-4-hydroxycinnamic acid,an optimal matrix to highly absorb the laser radiation at 405 nm,and a very thin-layer chemical film mainly containing drug molecule was transferred to the acceptor glass ***,MALDI MSI was performed on the chemical film without additional sample *** major advantage of LACT is to minimize ionization competition/suppression from the tissue itself by removing abundant endogenous lipid and protein *** superior performance of LACT led to the successful visualization of regional distribution patterns of 16 CNS drugs in the mouse ***,the dynamic spatial changes of risperidone and its metabolite were visualized over a 24-h ***,the brain-to-plasma(B/P)ratio could be obtained according to MALDI MSI results,providing an alternative means to assess brain penetration in drug discovery.