Waters XEVO G2-XS QTOF

Importance of the Topic

High-resolution, accurate-mass Time-of-Flight (Tof) mass spectrometry has become indispensable for laboratories tackling complex sample matrices. Enhanced sensitivity and selectivity enable detection of low-level analytes, confident compound identification, and reliable quantification in fields ranging from pharmaceutical development to environmental monitoring and metabolomics.

Objectives and Overview of the Study

This summary presents the capabilities and performance of the Xevo G2-XS QTof system, illustrating how its advanced ion optics, collision cell design, and acquisition modes deliver exceptional data quality. The document outlines the system’s design philosophy, key technologies, and practical outcomes in terms of resolution, sensitivity, robustness, and workflow integration.

Methodology and Instrumentation

Analytical methods were built around ultra-performance liquid chromatography (UPLC) coupled to the Xevo G2-XS QTof mass spectrometer. Core technologies include:

• StepWave ion optics for improved ion transmission and removal of neutral contaminants.
• XS Collision Cell providing narrow, focused ion beams for enhanced sensitivity and resolution.
• QuanTof detector geometry offering high dynamic range and mass accuracy independent of scan speed.

Data acquisition modes demonstrated include UPLC/Tof-MRM for targeted quantitation, MS^E for comprehensive precursor–fragment data, and FastDDA for intelligent MS/MS screening.

Main Results and Discussion

Key performance highlights:

• Mass resolution >40,000 FWHM across rapid scan rates, maintaining chromatographic peak fidelity (1.5 s at 10% height).
• Sensitivity gains >15× with XS Collision Cell relative to prior designs, enabling detection of femtogram-level analytes.
• Quantitative linearity down to sub-fg loadings in Tof-MRM mode (R² ≥ 0.995) and >10× improvement in signal-to-noise versus standard MS.
• Robustness demonstrated by 5% RSD over 500 injections of verapamil in plasma, with minimal maintenance downtime.
• Mass accuracy below 1 ppm RMS across hundreds of replicates, ensuring confident compound assignment.

Benefits and Practical Applications

The Xevo G2-XS QTof delivers:

• Streamlined workflows via IntelliStart automation for calibration, system checks, and monitoring.
• Versatile ion source architecture supporting ESI, APCI, APPI, nanoFlow, DESI, REIMS and more, ready within minutes.
• Seamless informatics integration with MassLynx or UNIFI for data processing, visualization, and reporting.

These features support both routine QA/QC tasks and advanced research including metabolite profiling, drug discovery, and biomarker characterization.

Future Trends and Opportunities

Emerging developments will leverage the platform’s universal source design to incorporate ambient and imaging ionization methods, single-cell analysis, and real-time data interrogation with machine learning. Enhanced connectivity to laboratory information management systems and cloud-based analytics will further accelerate decision-making.

Conclusion

The Xevo G2-XS QTof system represents a significant advancement in benchtop high-resolution mass spectrometry. Its combination of sensitivity, resolution, robustness, and workflow simplicity addresses the evolving needs of modern analytical laboratories, enabling deeper insight and faster, more reliable results.

References

• Waters Corporation. StepWave – Enhancing MS Sensitivity and Robustness. White Paper 720004175en.
• Waters Corporation. The XS Collision Cell from Waters: Increased Sensitivity and Resolution for Time-of-Flight Mass Spectrometry. White Paper 720005071en.
• Waters Corporation. QuanTof: High-Resolution, Accurate-Mass, Quantitative oaTof MS Technology. White Paper 720004545en.
• Waters Corporation. An Overview of the Principles of MS^E: The Engine that Drives MS Performance. White Paper 720004036en.