Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Neuroscience

Background:

• Traditional tissue analysis methods like HPLC-MS lose spatial information and struggle with blood contamination.
• Assessing drug penetration, especially into the brain, requires techniques that preserve spatial context.
• Liquid extraction surface analysis mass spectrometry (LESA-MS) offers a solution for spatially resolved tissue analysis.

Purpose of the Study:

• To utilize LESA-MS as a mass spectrometry imaging (MSI) tool for mapping xenobiotic and endogenous compound distribution.
• To assess drug penetration across the blood-brain barrier using LESA-MSI.
• To compare LESA-MSI with traditional homogenization and MALDI-MSI for drug distribution analysis.

Main Methods:

• LESA-MS was employed as an MSI tool, analyzing discrete points at 1 mm resolution across rat brain tissue sections.
• Drugs were administered orally and intravenously to rats, with whole brains snap-frozen for subsequent sectioning and analysis.
• Comparative analysis was performed using LESA-MSI, MALDI-MSI, and traditional homogenization techniques.

Main Results:

• LESA-MSI successfully mapped the distribution of both marginally and highly penetrative compounds.
• MALDI-MSI effectively mapped highly penetrative compounds but lacked sensitivity for marginally penetrative ones.
• LESA-MSI identified measurable drug penetration in cases where homogenization methods indicated non-penetration.

Conclusions:

• LESA-MSI is a valuable tool for assessing drug distribution and blood-brain barrier penetration with high spatial resolution.
• LESA-MSI complements MALDI-MSI, particularly for detecting compounds with low tissue penetration.
• LESA-MSI offers superior sensitivity and accuracy compared to traditional homogenization for evaluating drug penetration.