Neuroprotective potential of Linezolid: a quantitative and distribution study via mass spectrometry.
A study was undertaken to determine the neuroprotective potential of Linezolid (LIN) in an animal model. Female Sprague-Dawley rats were either given a single (100 mg/kg) dose or treated daily for 4 weeks. A validated LC-MS/MS method was used to measure LIN levels in plasma and brain, this was paired with mass spectrometry imaging to determine the tissue spatial distribution of the drug. The results showed that after a single dose there was poor penetration of the drug into the brain. With multiple doses there were high tissue levels, with the drug reaching steady state in subsequent weeks. LIN displayed a promising distribution pattern with localisation in the brainstem. Systemic circulation is fed into the brain by the carotid and vertebral arteries which enter through the brain stem, therefore high drug concentrations is this area may protect against infectious agents entering via this route.
Catalysis and Peptide Research Unit, University of KwaZulu-Natal, E-Block, 6th Floor, Room E1-06-016, Westville Campus, Durban, South Africa.
Sooraj
S
Baijnath
Catalysis and Peptide Research Unit, University of KwaZulu-Natal, E-Block, 6th Floor, Room E1-06-016, Westville Campus, Durban, South Africa.
Adeola
A
Shobo
Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
Linda A
LA
Bester
Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
Sanil D
SD
Singh
Catalysis and Peptide Research Unit, University of KwaZulu-Natal, E-Block, 6th Floor, Room E1-06-016, Westville Campus, Durban, South Africa.
Gert
G
Kruger
Catalysis and Peptide Research Unit, University of KwaZulu-Natal, E-Block, 6th Floor, Room E1-06-016, Westville Campus, Durban, South Africa.|Science for Life Laboratory, Drug Discovery and Development Platform and Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Per I
PI
Arvidsson
Catalysis and Peptide Research Unit, University of KwaZulu-Natal, E-Block, 6th Floor, Room E1-06-016, Westville Campus, Durban, South Africa.
Tricia
T
Naicker
Catalysis and Peptide Research Unit, University of KwaZulu-Natal, E-Block, 6th Floor, Room E1-06-016, Westville Campus, Durban, South Africa. govenderthav@ukzn.ac.za.
Thavendran
T
Govender
D000818:Animals; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid; D005260:Female; D000069349:Linezolid / Q000493:pharmacokinetics*; D013058:Mass Spectrometry / Q000379:methods; D018696:Neuroprotective Agents / Q000493:pharmacokinetics*; D051381:Rats; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D018696:Neuroprotective Agents; D000069349:Linezolid
Brain; LC–MS/MS; Linezolid; MSI; Molecular histology; Neuroprotection