IMPROVED SELECTIVITY AND ACQUISITION SPEED USING DESI QUADRUPOLE BASED MASS SPECTROMETER

Significance of the Topic

Mass spectrometry imaging based on desorption electrospray ionization combined with multiple reaction monitoring on a quadrupole mass spectrometer offers rapid, highly selective molecular mapping of drugs and metabolites directly from tissue sections. This capability supports pharmacokinetic, toxicological and drug distribution studies in pharmaceutical research and development by delivering high specificity with minimal sample preparation

Objectives and Study Overview

The study aimed to demonstrate improved selectivity and acquisition speed using the DESI XS source mounted on a Xevo TQ-XS tandem quadrupole mass spectrometer. Specific goals included evaluation of detection limits, linearity of response for six drug standards on tissue sections and imaging of four orally dosed drugs and their primary metabolites in mouse brain, kidney and liver sections

Methodology and Instrumentation

Sample Preparation

• Standard mix of propranolol, olanzapine, erlotinib, moxifloxacin, terfenadine and irinotecan prepared in methanol water solution
• Tenfold serial dilutions from 1 pg to 10 000 pg per spot on 16 micrometer porcine liver sections
• Mouse tissues collected at control, 2 and 6 hours post dose for four drug compounds

Instrumentation

• DESI XS source with high performance sprayer operated at 0.8 kV with nitrogen nebulizing gas at 10 psi
• Xevo TQ-XS tandem quadrupole mass spectrometer in positive ion mode
• HDi high definition imaging software plugin for co registration of optical images and definition of MRM transitions
• MRM acquisition parameters: pixel size 50 micrometer, scan rate 10 pixels per second, cone voltage 20 V, source temp 100 °C

Main Results and Discussion

Spotting experiments on liver tissue achieved detection limits between 10 pg and 100 pg for all six pharmaceuticals. Calibration curves generated from region of interest intensity data exhibited excellent linearity with R2 values greater than 0.9997. In tissue imaging of dosed animals, all four parent drugs were localized in brain, kidney and liver sections and key metabolites such as hydroxyolanzapine, desmethylerlotinib and carboxyterfenadine were detected selectively in relevant organs. RGB overlay images demonstrated clear spatial distribution of compounds

Benefits and Practical Applications

The combined DESI XS MRM approach provides

• Enhanced analytical specificity through targeted reaction monitoring
• High throughput imaging with acquisition speeds up to 10 pixels per second
• Minimal sample preparation and ambient analysis
• Robust quantitation with low picogram sensitivity on tissue

These features support applications in drug distribution studies, metabolic profiling and biomarker localization in preclinical research

Future Trends and Opportunities

Advances may include

• Integration with higher multiplexing MRM methods to expand the panel of target analytes
• Improvements in spatial resolution by optimized spray geometry and acquisition software
• Automation of data processing pipelines for real time image reconstruction
• Application of DESI MRM imaging to clinical tissue specimens for translational research

Conclusion

The implementation of a DESI XS source on a Xevo TQ-XS mass spectrometer with targeted MRM imaging delivers rapid, sensitive and highly selective molecular maps of drugs and metabolites in tissue. The workflow combines simplified software control, low picogram detection limits and excellent linearity, making it a powerful tool for pharmaceutical imaging studies

Reference

1 L Lamont D Hadavi B Viehmann B Flinders R M A Heeren R Vreeken T Porta Siegel Quantitative mass spectrometry imaging of drugs and metabolites a multiplatform comparison Analytical and Bioanalytical Chemistry 413 2779 2791 2021