title: Visualization of Time-Dependent Distribution of Rifampicin in Rat Brain Using MALDI MSI and Quantitative LCMS/MS.
abstract: 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.
authors.affiliation: 1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Adeola
authors.initials: A
authors.lastname: Shobo
authors.affiliation: 1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Dominika
authors.initials: D
authors.lastname: Bratkowska
authors.affiliation: 1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Sooraj
authors.initials: S
authors.lastname: Baijnath
authors.affiliation: 1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Suhashni
authors.initials: S
authors.lastname: Naiker
authors.affiliation: 2 Biomedical Resource Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Linda A
authors.initials: LA
authors.lastname: Bester
authors.affiliation: 2 Biomedical Resource Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Sanil D
authors.initials: SD
authors.lastname: Singh
authors.affiliation: 3 School of Chemistry and Physics, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Glenn Eamond Mitchell
authors.initials: GE
authors.lastname: Maguire
authors.affiliation: 1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Hendrik Gert
authors.initials: HG
authors.lastname: Kruger
authors.affiliation: 1 Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus, Durban, South Africa .
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000032:analysis* / Q000378:metabolism* / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D012293:Rifampin