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

Abstract

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.

Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono‐infected pregnant women during labor by ultra‐performance liquid chromatography/tandem mass spectrometry

“…A summary of the representative methods for the analysis of TFV is presented in Table . Although several methods have been developed to determine TFV in different biological samples such as plasma, urine, cerebrospinal fluid, brain and even seminal plasma, to our knowledge, this is the first study on a validated method to determine TFV in human amniotic fluid. Two previous researchers described the quantification of TFV in amniotic fluid with a LLOQ of 5 ng/mL, but detailed accuracy was not determined in those studies.…”

A microscopy-based small molecule screen in primary neurons reveals neuroprotective properties of the FDA-approved anti-viral drug Elvitegravir

“…As an FDA-approved drug that has been used in a large number of patients for many years, the safety profile of Elvitegravir is well established. For a potential treatment of neurodegenerative diseases, however, considerable drug development appears necessary, including, e.g., an improvement of Elvitegravir’s blood-brain-barrier permeability [ 40 , 41 ]. Toxic side-effects of prolonged Elvitegravir exposure are likely due to its activation of the integrated stress response (ISR) [ 27 ].…”

Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs

“…After blood collection, animals were perfused with saline. 42 Following perfusion, rat brain tissues were rapidly dissected after the termination, washed with saline to avoid any possible blood contamination, and snap-frozen in liquid nitrogen (−80 °C). All collected brains were stored at −80 °C until further treatment.…”