Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study.

Authors:
Chiedza F Munyeza
Chiedza F Munyeza
University of KwaZulu-Natal
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
Linda A Bester
Linda A Bester
University of KwaZulu-Natal
Pietermaritzburg | South Africa

Xenobiotica 2016 31;46(5):385-92. Epub 2015 Aug 31.

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

1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain. 2. The time-dependent distribution was investigated after an i.p. dose of 25 mg/kg at 0, 5, 30, 120, 240, 360 and 480 min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte. 3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (Cmax) of 1034.9 ng/mL at 240 min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5 min and its slow elimination after 360-min postdose. 4. Our findings confirm that MALDI MSI provides an advanced, label-free and faster alternative technique for xenobiotic distribution such as DOX in tissues, making it an essential drug discovery tool for other possible neuroprotective agents.

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http://dx.doi.org/10.3109/00498254.2015.1081307DOI Listing
November 2016
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