Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study.
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.
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Chiedza F
CF
Munyeza
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Adeola
A
Shobo
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Sooraj
S
Baijnath
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Dominika
D
Bratkowska
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Suhashni
S
Naiker
b Biomedical Resource Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa.
Linda A
LA
Bester
b Biomedical Resource Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa.
Sanil D
SD
Singh
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Glenn E M
GE
Maguire
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Hendrik G
HG
Kruger
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Tricia
T
Naicker
a Catalysis and Peptide Research Unit, University of KwaZulu-Natal , Westville Campus , Durban , South Africa and.
Thavendran
T
Govender
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002853:Chromatography, Liquid; D004318:Doxycycline / Q000493:pharmacokinetics*; D055808:Drug Discovery; D005260:Female; D007249:Inflammation; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000900:Anti-Bacterial Agents; D004318:Doxycycline
Doxycycline; mass spectrometric imaging; rat brain tissues