Improved molecular detection and acquisition speed using DESI mass spectrometry imaging quadrupole based mass spectrometer

Significance of the Topic

Desorption electrospray ionization mass spectrometry imaging (DESI MSI) enables direct spatial mapping of molecules in tissue without complex sample preparation. Integrating DESI with tandem quadrupole (TQ) instrumentation can combine rapid image acquisition with high sensitivity and specificity, addressing key challenges in pharmaceutical distribution studies, metabolite profiling, and targeted bioanalysis.

Objectives and Study Overview

This study evaluated detection limits and imaging speed for small-molecule drugs and their metabolites in tissue sections using a quadrupole-based mass spectrometer. Researchers compared targeted multiple reaction monitoring (MRM) on a Xevo TQ-XS to untargeted MS on a Xevo G2-XS Q-Tof, assessing calibration, linearity, and spatial distribution in both spotted and dosed animal tissues.

Methodology and Instrumentation

Sample preparation included spotting known amounts (1–10 000 pg) of six pharmaceuticals on 16 µm porcine liver sections and analyzing mouse brain, kidney, and liver from animals dosed with four drugs at defined time points.

• Mass spectrometers: Xevo TQ-XS in MRM mode, Xevo G2-XS Q-Tof in MS mode.
• DESI source: High-Performance DESI (DESI XS) sprayer.
• Software: HDI 1.6 for co-registration of optical and mass spectral images.
• Acquisition speed: 10 pixels per second, 20 MRM transitions defined.

Main Results and Discussion

All six pharmaceuticals were detected on tissue at 10–100 pg levels with excellent calibration linearity. Targeted MRM imaging on the Xevo TQ-XS revealed four parent drugs and five metabolites across dosed tissue sections. Comparative data demonstrated that MRM provided higher sensitivity and specificity than untargeted MS, enabling clear spatial localization even at high scan speeds.

Benefits and Practical Applications

• Enhanced sensitivity: pg-level detection of drugs and metabolites directly on tissue.
• High specificity: reduced background through MRM transitions.
• Rapid imaging: 10 pixels/s supports high-throughput studies.
• Versatility: applicable to pharmacokinetic profiling, drug distribution, and targeted biomarker analysis.

Future Trends and Applications

Advances may include coupling DESI MSI with higher-resolution mass analyzers, real-time data processing via machine learning, expanded metabolite libraries for untargeted screening, and translation to clinical tissue imaging workflows for precision medicine and QA/QC in pharmaceutical development.

Conclusion

The combination of DESI XS and a tandem quadrupole mass spectrometer delivers rapid, sensitive, and specific MSI for targeted drug and metabolite analysis in tissues. This approach enhances throughput and data quality for pharmaceutical research and applied bioanalysis.

References

Claude E., Rao W., Takats Z., Jones E. Improved molecular detection and acquisition speed using DESI mass spectrometry imaging. Waters Corporation, 2021.