Revolutionize Metabolite Identification with Cyclic IMS

Importance of the Topic

Understanding metabolite structures and dynamics is critical for pharmaceutical research and development. High-resolution ion mobility separation of isomeric species improves identification confidence and accelerates reaction monitoring workflows without the need for liquid chromatography.

Objectives and Study Overview

This study demonstrates the advantages of cyclic ion mobility spectrometry (cIMS) in enhancing metabolite discovery, structural elucidation, and real-time monitoring of chemical transformations. Collaborative experiments with industry partners showcase its application in drug metabolism and high-throughput screening.

Methodology

cIMS employs multiple passes of ion packets through a mobility cell to increase separation resolution. Integration with a time-of-flight mass analyzer delivers high sensitivity, resolution exceeding 100 000 FWHM and mass accuracy below 1 ppm. Multi-stage IMSn and slicing techniques allow targeted refinement of ion populations for detailed structural insights.

Used Instrumentation

• Cyclic IMS device with variable pass capability
• Multi-stage IMSn module
• Time-of-flight mass spectrometer with >100 000 FWHM resolution
• Automated infusion and calibration system for real-time monitoring

Main Results and Discussion

Increasing the number of cIMS passes revealed additional oxidized isomers of ranitidine and buspirone not detectable in single-pass analyses. IMSn slicing enabled selective enrichment and investigation of acyl glucuronide isomers. Real-time infusion monitoring captured acyl migration kinetics, highlighting potential for rapid reaction screening.

Benefits and Practical Applications

• Enhanced discovery of co-eluting and isomeric metabolites
• Nonchromatographic monitoring of metabolic and chemical reaction kinetics
• Improved confidence in metabolite identification through consistent collisional cross section values
• Streamlined workflows for routine pharmaceutical analysis

Future Trends and Potential Applications

Ongoing advancements in IMSn techniques will further refine structural characterization of complex metabolites. Integration of predictive modeling for collisional cross section values could accelerate metabolite annotation. Broader adoption in regulatory and industrial settings will support robust, cross-platform data comparability.

Conclusion

Cyclic IMS presents a powerful platform for metabolite identification and monitoring, combining ultra-high mobility resolution with flexible IMSn workflows. Its implementation reduces reliance on conventional separations and enhances both discovery and routine screening in pharmaceutical research.

References

1. Higton D Wilson I et al 2021 The use of Cyclic Ion Mobility Spectrometry Mass Spectrometry to Study the Intramolecular Transacylation of Diclofenac Acyl Glucuronide Analytical Chemistry 10.1021/acs.analchem.0c04487