Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry

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 (Cmaxbrain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmaxbrain 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.