RATIONALE: The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood-brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS. METHODS: The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague-Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix-assisted laser desorption/ionization (MALDI) MSI. RESULTS: LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmax brain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmax brain of 54.5 ng/g. MALDI-MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex. CONCLUSIONS: LC/MS/MS and MALDI-MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI-MSI for direct visualization of pharmaceutical drugs in situ.
RATIONALE: The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood-brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS. METHODS: The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague-Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix-assisted laser desorption/ionization (MALDI) MSI. RESULTS: LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmax brain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmax brain of 54.5 ng/g. MALDI-MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex. CONCLUSIONS: LC/MS/MS and MALDI-MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI-MSI for direct visualization of pharmaceutical drugs in situ.
Authors: Simon F Merz; C Peter Bengtson; Clara Tepohl; Anna M Hagenston; Hilmar Bading; Carlos Bas-Orth Journal: Mol Brain Date: 2020-09-14 Impact factor: 4.041