期刊
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
卷 25, 期 11, 页码 1600-1608出版社
WILEY-BLACKWELL
DOI: 10.1002/rcm.5021
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In pharmacology and toxicology, localization of the distribution of a drug molecule in its target tissue provides very important in vivo biological information. Traditionally, this has been examined using autoradiography (ARG). However, there are significant limitations in this application. One is the synthesis and use of radiolabeled compounds, the other is that the image generated expresses an undifferentiated mixture of the parent drug and/or its metabolites. The objective of the study was to define the specific distribution of the parent drug in rat ocular tissue containing melanin (e.g. the retina) using non-labeled chloroquine by MALDI Imaging tandem mass spectrometry (MS/MS). After single oral administration (at 20 mg/kg) of chloroquine, sections (10 mu m) of rat eye tissue were prepared at 24 h. The MS system used was a quadrupole time-of flight (Q-TOF) tandem mass spectrometer (MALDI Synapt (TM), Waters, Milford, MA, USA). Tissue sections were sprayed with CHCA (alpha-cyano-4-hydroxycinnamic acid, 5mg/mL) in 80% acetonitrile (ACN) containing 5% formic acid (FA) using either a manual sprayer (airbrush) or an automated sprayer (TM-Sprayer (TM), HTX Technologies, Carrboro, NC, USA). Chloroquine was readily detected in the MS/MS mode by monitoring one of its major fragment ions (m/z 247.10) and imaged through the rat eye tissue. The image of the specific distribution within the retina in the rat eye tissue was confirmed, and found to be similar to autoradiograms after oral administration of (14)C-chloroquine reported previously. Copyright (C) 2011 John Wiley & Sons, Ltd.
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