Analytical Performance Evaluation of New DESI Enhancements for Targeted Drug Quantification in Tissue Sections

Abstract

Desorption/ionization (DI)-mass spectrometric (MS) methods offer considerable advantages of rapidity and low-sample input for the analysis of solid biological matrices such as tissue sections. The concept of desorption electrospray ionization (DESI) offers the possibility to ionize compounds from solid surfaces at atmospheric pressure, without the addition of organic compounds to initiate desorption. However, severe drawbacks from former DESI hardware stability made the development of assays for drug quantification difficult. In the present study, the potential of new prototype source setups (High Performance DESI Sprayer and Heated Transfer Line) for the development of drug quantification assays in tissue sections was evaluated. It was demonstrated that following dedicated optimization, new DESI XS enhancements present promising options regarding targeted quantitative analyses. As a model compound for these developments, ulixertinib, an inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2 was used.

Applications of ambient ionization mass spectrometry in 2022: An annual review

“…Several other studies have used DESI-MS imaging to study the distribution of drugs in tissues, including acetaminophen and its metabolites in the mouse liver 121 and extracellular signal-regulated kinase inhibitors in mouse brain tissues. 122 Finally, another recent study utilized SESI-MS for the real-time detection of inhaled aerosols in exhaled breath for the purpose of studying the aerosolization performance of inhaled drug products. 123 The detection of pharmaceuticals in animals also has implications for environmental challenges.…”

“…The study imaged the immunosuppressant cyclosporine and its metabolites throughout the internal organs, demonstrating the drug itself was primarily detected in the pancreas and liver, whereas metabolites were primarily found in the intestines. Several other studies have used DESI‐MS imaging to study the distribution of drugs in tissues, including acetaminophen and its metabolites in the mouse liver 121 and extracellular signal‐regulated kinase inhibitors in mouse brain tissues 122 . Finally, another recent study utilized SESI‐MS for the real‐time detection of inhaled aerosols in exhaled breath for the purpose of studying the aerosolization performance of inhaled drug products 123 …”

Desorption Kinetics Evaluation for the Development of Validated Desorption Electrospray Ionization-Mass Spectrometric Assays for Drug Quantification in Tissue Sections

“…Using adapted considerations for method validation, on-surface MS methods are in the process of being considered as reliable members of the panel of methods for drug quantification in (pre)clinical studies [13]. Method validation has already been largely approached 2 of 14 for MALDI imaging [14] and profiling approaches [15], and DESI is in the process of being considered as method of choice for method development [16].…”

“…DESI-MS has long suffered from the lack of robust hardware for the development of drug quantification assays in tissue sections [17,18], but recent enhancements have been proven to be highly valuable for the development of methods that follow the requirements of regulatory guidelines [16,19]. The most recent advances were performed in profiling mode, in which analyses are performed in selected locations with known histology.…”

“…Drugs from dosed tissues are extracted from the tissue section, while IS, or the reference compounds used for CALs and QCs, are deposited at its surface. A suboptimal solvent-based extraction of drugs from the tissue would thus lead to an underestimation of their concentration [16,21].…”