Bedaquiline has potential for targeting tuberculosis reservoirs in the central nervous system

Abstract

Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.

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

“…The application of MSI to investigate small‐molecule spatial distribution was first demonstrated in 2003 following imaging of two anti‐cancer drugs, SCH 226 374 and compound A, in rat brain . Since then, a wide range of small molecules have been mapped using MSI in various biological tissues . MSI of antiretroviral drugs in various biological tissues has been done; however, there are no MSI‐related studies showing the spatial distribution of elvitegravir in biological tissues, and few studies have demonstrated the use of MSI to map tenofovir in situ .…”

“…The matrix solution was prepared by dissolving CHCA in 50% acetonitrile, 0.1% trifluoroacetic acid to make up a final concentration of 7 mg/mL. For matrix and ISTD application, a previously described standardized ImagePrep (Bruker Daltonics, Bremen, Germany) five‐cycle method was used, each cycle consisting of three steps including spraying, incubation and drying . An automated ImagePrep spraying equipment uniformly deposited the matrix onto the tissue in a form of an aerosol.…”

“…Sample preparation followed the same method used in our previous studies. 13,14 Briefly, this involved analyte extraction by protein precipitation followed by a modified solid-phase extraction (SPE) method using a HybridSPE-Phospholipid (30 mg, 1 mL) (Supelco-Sigma, St Louis, MO, USA) SPE cartridge. The extract was collected into autosampler vials and vortexed briefly, before injecting 5 μL into the LC/MS/MS system.…”

“…For matrix and ISTD application, a previously described standardized ImagePrep (Bruker Daltonics, Bremen, Germany) five-cycle method was used, each cycle consisting of three steps including spraying, incubation and drying. 13,14,17 An automated ImagePrep spraying equipment uniformly deposited the matrix onto the tissue in a form of an aerosol. An aerosol was generated by a vibrating spray generator producing tiny droplets with an average droplet size of ca 20 μm.…”

“…42 Since then, a wide range of small molecules have been mapped using MSI in various biological tissues. 13 43 Studies have shown that HIV primarily invades the cortical areas of the brain. [45][46][47] HIV has also been reported to invade the basal regions including areas like globus pallidus and the striatum region known as caudate putamen.…”