Tissue distribution of pretomanid in rat brain via mass spectrometry imaging

1. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) combines the sensitivity and selectivity of mass spectrometry with spatial analysis to provide a new dimension for histological analyses of the distribution of drugs in tissue. Pretomanid is a pro-drug belonging to...

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Bibliographic Details
Published in:Xenobiotica 2016-03, Vol.46 (3), p.247-252
Main Authors: Shobo, Adeola, Bratkowska, Dominika, Baijnath, Sooraj, Naiker, Suhashni, Somboro, Anou M., Bester, Linda A., Singh, Sanil D., Naicker, Tricia, Kruger, Hendrik G., Govender, Thavendran
Format: Article
Language:English
Subjects:
Animals
Antitubercular Agents - pharmacokinetics
Blood-Brain Barrier - metabolism
Brain - metabolism
Drug distribution
Female
MALDI MSI
nitroimidazole
Nitroimidazoles - pharmacokinetics
Prodrugs - pharmacokinetics
Rats
Rats, Sprague-Dawley
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tissue Distribution
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Summary:1. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) combines the sensitivity and selectivity of mass spectrometry with spatial analysis to provide a new dimension for histological analyses of the distribution of drugs in tissue. Pretomanid is a pro-drug belonging to a class of antibiotics known as nitroimidizoles, which have been proven to be active under hypoxic conditions and to the best of our knowledge there have been no studies investigating the distribution and localisation of this class of compounds in the brain using MALDI MSI. 2. Herein, we report on the distribution of pretomanid in the healthy rat brain after intraperitoneal administration (20 mg/kg) using MALDI MSI. Our findings showed that the drug localises in specific compartments of the rat brain viz. the corpus callosum, a dense network of neurons connecting left and right cerebral hemispheres. 3. This study proves that MALDI MSI technique has great potential for mapping the pretomanid distribution in uninfected tissue samples, without the need for molecular labelling.
ISSN:0049-8254
1366-5928
DOI:10.3109/00498254.2015.1067935