Simultaneous positive and negative HRAM acquisition using a Q-TOF mass spectrometer with ultra-high mass stability

Significance of the Topic

In high-resolution accurate mass (HRAM) analysis, simultaneous positive and negative ion acquisition can double throughput but has been hindered by mass accuracy issues caused by voltage instability during polarity switching. Establishing a reliable method to compensate for these instabilities is vital for efficient and precise compositional analysis in fields ranging from pharmaceutical QA/QC to environmental monitoring.

Study Objectives and Overview

This work aimed to develop and validate a correction algorithm to quickly stabilize mass measurements after switching ionization polarity on a Shimadzu LCMS-9050 Q-TOF system. The goal was to achieve low-ppm mass accuracy in both modes with minimal delay, enabling a single-run dual-polarity HRAM workflow.

Methodology and Instrumentation

Researchers introduced a time-dependent correction term into the conventional flight-time-to-m/z conversion formula to account for high-voltage decay after polarity switching. Method highlights:

• Polarity switching time optimized to 600 milliseconds
• Correction function f(tp, ta), where tp is time after switching and ta is acquisition time
• Validation over a wide m/z range using sodium iodide calibration ions

Main Results and Discussion

By applying the modified equation, mass errors fell below 1 ppm in positive mode and under 3 ppm in negative mode at 600 ms switching intervals. Long-term stability tests over 24 hours with antibiotic standards showed errors consistently within ±3 ppm, demonstrating robust performance without frequent recalibration. Graphical data indicate substantial improvement over the uncorrected approach, reducing stabilization time from seconds to under one second.

Benefits and Practical Applications

The enhanced algorithm allows simultaneous positive/negative HRAM analysis in a single LC-MS run, effectively doubling sample throughput. Key advantages include:

• Reduced analysis time and resource use
• Maintained high mass accuracy for reliable compound identification
• Applicability to diverse analytical fields such as metabolomics, pharmaceuticals, and environmental testing

Future Trends and Potential Applications

Emerging applications may integrate this fast-switching technique with data-independent acquisition strategies and advanced software workflows for automated high-throughput screening. Further refinements could extend the approach to even faster switching intervals and other mass spectrometer platforms.

Conclusion

The novel correction algorithm implemented on the Shimadzu LCMS-9050 Q-TOF system effectively compensates for high-voltage instability, achieving low-ppm accuracy in both ionization modes with minimal delay. This innovation paves the way for efficient, high-throughput HRAM analyses in routine laboratory operations.

Reference

Oshiro T, Miyazaki Y, Nakanishi T, Toyama A, Okumura D. Simultaneous positive and negative HRAM acquisition using a Q-TOF mass spectrometer with ultra-high mass stability. Shimadzu technical report, 2022.