In situ label-free visualization of tissue distributions of salidroside in multiple mouse organs by MALDI-MS imaging

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.