A quantitation method for mass spectrometry imaging

TLDR

The method offers a quantitative approach for mass spectrometry imaging, addressing key considerations for pharmaceutical analysis. The study applies the method to quantify olanzapine distribution in rat liver tissue. Tissue sections from olanzapine‑treated rat livers were homogenized and analyzed by LC/MS/MS, and the resulting concentrations were correlated with MALDI‑MSI ion counts to establish a conversion factor. A strong linear correlation (R² = 0.979) between LC/MS/MS concentrations and MSI ion counts yielded a conversion factor of 6.3 ± 0.23 fg/ion, enabling quantitative pixel‑level analysis.

Abstract

A new quantitation method for mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) has been developed. In this method, drug concentrations were determined by tissue homogenization of five 10 µm tissue sections adjacent to those analyzed by MSI. Drug levels in tissue extracts were measured by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The integrated MSI response was correlated to the LC/MS/MS drug concentrations to determine the amount of drug detected per MSI ion count. The study reported here evaluates olanzapine in liver tissue. Tissue samples containing a range of concentrations were created from liver harvested from rats administered a single dose of olanzapine at 0, 1, 4, 8, 16, 30, or 100 mg/kg. The liver samples were then analyzed by MALDI-MSI and LC/MS/MS. The MALDI-MSI and LC/MS/MS correlation was determined for tissue concentrations of ~300 to 60,000 ng/g and yielded a linear relationship over two orders of magnitude (R(2) = 0.9792). From this correlation, a conversion factor of 6.3 ± 0.23 fg/ion count was used to quantitate MSI responses at the pixel level (100 µm). The details of the method, its importance in pharmaceutical analysis, and the considerations necessary when implementing it are presented.