title: MALDI MSI and LC-MS/MS: Towards preclinical determination of the neurotoxic potential of fluoroquinolones.
abstract: 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.
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Adeola
authors.initials: A
authors.lastname: Shobo
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Sooraj
authors.initials: S
authors.lastname: Baijnath
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Dominika
authors.initials: D
authors.lastname: Bratkowska
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Suhashni
authors.initials: S
authors.lastname: Naiker
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Anou M
authors.initials: AM
authors.lastname: Somboro
authors.affiliation: Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Bester
authors.affiliation: Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Sanil D
authors.initials: SD
authors.lastname: Singh
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Tricia
authors.initials: T
authors.lastname: Naicker
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics*; D000077734:Gatifloxacin; D008168:Lung / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D059005:Topoisomerase II Inhibitors / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D059005:Topoisomerase II Inhibitors; D000077734:Gatifloxacin
keywords: fluoroquinolones; liquid chromatography-tandem mass spectrometry (LC-MS/MS); matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI)