MALDI MSI and LC-MS/MS: Towards preclinical determination of the neurotoxic potential of fluoroquinolones.

Authors:
Dr Adeola Shobo, PhD
Dr Adeola Shobo, PhD
McGill University
Dr
Montreal , McGill University | Canada
Sooraj Baijnath
Sooraj Baijnath
University of KwaZulu-Natal
South Africa
Dominika Bratkowska
Dominika Bratkowska
Universitat Rovira i Virgili
Spain
Anou M Somboro
Anou M Somboro
School of Health Sciences
Linda A Bester
Linda A Bester
University of KwaZulu-Natal
Pietermaritzburg | South Africa
Tricia Naicker
Tricia Naicker
School of Health Sciences

Drug Test Anal 2016 Aug 18;8(8):832-8. Epub 2015 Sep 18.

Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.

Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic microbes associated with respiratory and meningeal infections. The potential toxicity of this class of chemical agents is a source of major concern and is becoming a global issue. The aim of this study was to develop a method for the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-Dawley rats, via Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a sensitive LC-MS/MS method to quantify gatifloxacin in plasma, lung, and brain homogenates. A pharmacokinetic profile was observed where there is a double peak pattern; a sharp initial increase in the concentration soon after dosing followed by a steady decline until another increase in concentration after a longer period post dosing in all three biological samples was observed. The imaging results showed the drug gradually entering the brain via the blood brain barrier and into the cortical regions from 15 to 240 min post dose. As time elapses, the drug leaves the brain following the same path as it followed on its entry and finally concentrates at the cortex. Copyright © 2015 John Wiley & Sons, Ltd.

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http://dx.doi.org/10.1002/dta.1862DOI Listing
August 2016
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