Visualization of Time-Dependent Distribution of Rifampicin in Rat Brain Using MALDI MSI and Quantitative LCMS/MS.

Authors:
Dr Adeola Shobo, PhD
Dr Adeola Shobo, PhD
McGill University
Dr
Montreal , McGill University | Canada
Dominika Bratkowska
Dominika Bratkowska
Universitat Rovira i Virgili
Spain
Sooraj Baijnath
Sooraj Baijnath
University of KwaZulu-Natal
South Africa
Linda A Bester
Linda A Bester
University of KwaZulu-Natal
Pietermaritzburg | South Africa
Hendrik Gert Kruger
Hendrik Gert Kruger
University of KwaZulu-Natal
Pietermaritzburg | South Africa

Assay Drug Dev Technol 2015 Jun 12;13(5):277-84. Epub 2015 Jun 12.

1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .

Rifampicin (RIF) is a major component for short-course chemotherapy against tuberculosis, since it is active against rapidly metabolizing as well as dormant bacteria. According to the Lipinski rules, RIF should not enter the blood-brain barrier. Visualization of tissue drug distribution is of major importance in pharmacological studies; thus, far imaging of RIF in the brain has been limited to positron emission tomography. We propose using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques as a suitable alternative for the visualization and localization of drug tissue distribution. Using the liquid chromatography mass spectrometric (LCMS) technique, we were able to quantify the concentrations of RIF in the uninfected rat brain; we paired this with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to show the time-dependent manner in which RIF is able to enter the brain. Our results show that even at the minute concentrations measured with LCMS/MS we were able visualize the drug and show its exact distribution in the rat brain. Other available methods require nuclear labeling and the detection of gamma rays produced by labeled compounds to visualize the compound and its localization; MALDI MSI is a more recently developed technique, which can provide detailed information on drug distribution in tissues when compared to other imaging techniques. This study shows that without any requirement for complex preprocessing we are able to produce images with a relatively improved resolution and localization than those acquired using more complex imaging methods, showing MALDI MSI to be an invaluable tool in drug distribution studies.

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Source
http://dx.doi.org/10.1089/adt.2015.634DOI Listing
June 2015
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2 Citations
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