Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study
| Autor: | Adeola Shobo, Sooraj Baijnath, Tricia Naicker, Thavendran Govender, Linda A. Bester, Hendrik G. Kruger, Chiedza F. Munyeza, Dominika Bratkowska, Sanil D. Singh, Glenn E. M. Maguire, Suhashni Naiker |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Spectrometry Mass Electrospray Ionization Health Toxicology and Mutagenesis Cmax Toxicology Mass spectrometry Bioinformatics 01 natural sciences Biochemistry Rats Sprague-Dawley 03 medical and health sciences Drug Discovery medicine Distribution (pharmacology) Animals Pharmacology Doxycycline Inflammation Chromatography Chemistry 010401 analytical chemistry Brain Histology Imaging study General Medicine Rat brain Mass spectrometric 0104 chemical sciences Anti-Bacterial Agents Rats 030104 developmental biology Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Female medicine.drug Chromatography Liquid |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 46(5) |
| ISSN: | 1366-5928 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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