Thermo Scientific Q Exactive Focus Orbitrap LC-MS/MS System

Importance of the Topic

High-resolution accurate-mass (HRAM) liquid chromatography–mass spectrometry has become a cornerstone technique in analytical chemistry, delivering both qualitative confidence and quantitative precision. By offering detailed molecular information without extensive method optimization, HRAM LC-MS/MS systems enable laboratories across environmental, food safety, forensic, pharmaceutical, and metabolomics fields to address increasingly complex analytical challenges with reliability and efficiency.

Objectives and Overview of the Article

This document introduces the Thermo Scientific Q Exactive Focus hybrid quadrupole-Orbitrap LC-MS/MS system, designed to democratize HRAM analysis for routine applications. It outlines the system’s performance characteristics, robustness, and broad application scope, illustrating how a single, cost-effective platform can streamline both targeted quantitation and non-targeted screening workflows.

Methodology

Analytical workflows leverage full-scan high-resolution MS, data-dependent MS/MS, variable data-independent acquisition (vDIA), and parallel reaction monitoring (PRM). Fast polarity switching enhances compound coverage within a single run. Integrated software tools facilitate data acquisition, automated processing, statistical evaluation, and retrospective analysis.

Used Instrumentation

• Q Exactive Focus hybrid quadrupole-Orbitrap mass spectrometer
• Hyperbolic quadrupole mass filter
• C-Trap and higher-energy collisional dissociation (HCD) cell
• RF lens ion source
• Orbitrap mass analyzer (up to 70,000 resolution at m/z 200, <1 ppm mass accuracy)

Main Results and Discussion

• Mass accuracy and resolution: Achieved <1 ppm mass error and 70,000 resolution at m/z 200, enabling clear separation of analyte signals from complex matrix interferences.
• Dynamic range and sensitivity: Linear quantitative dynamic range spanning six orders of magnitude; detection limits down to low picogram and sub-ppb levels across diverse analyte classes.
• Robustness: Consistent peak intensity and mass accuracy over 900 injections of complex wheat extracts demonstrated system durability in routine use.
• Environmental and food safety: Multiplexed screening and quantitation of veterinary drug residues down to 0.1 ppb in meat, milk, and plasma matrices.
• Unknown screening: vDIA combined with TraceFinder and SIEVE software supports non-targeted workflows, differential analysis, and retrospective data mining for emerging contaminants.
• Forensic toxicology: Fast full-scan HRAM screening of urine for opiates and barbiturates, followed by PRM confirmation at low ng/mL levels with high selectivity.
• Pharma and bio-pharma: Quantitation of small molecules such as paroxetine at 10 pg/mL in plasma, demonstrating triple quadrupole-level sensitivity with HRAM selectivity.
• Metabolomics: Continuous 12-hour UHPLC-MS run of d5-hippuric acid exhibited stable mass accuracy (<1 ppm) and low variability, supporting large-scale metabolite profiling.

Benefits and Practical Applications

• Unified platform for targeted quantitation and untargeted screening reduces instrument footprint and method development time.
• High throughput capability for QA/QC laboratories in environmental monitoring, food safety, pharmaceutical analysis, and forensic toxicology.
• Integrated software ecosystem (TraceFinder, SIEVE, Compound Discoverer, ToxFinder) streamlines data processing, statistical evaluation, and reporting.
• Robust design ensures reliable performance in high-sample-volume routine environments.

Future Trends and Opportunities

Continued enhancement of vDIA methods, expansion of HRAM spectral libraries, and integration with machine learning for automated feature identification are poised to further empower retrospective data mining and real-time decision making. Emerging ion source designs and faster Orbitrap scan rates will enable deeper coverage of complex biological and environmental samples.

Conclusion

The Thermo Scientific Q Exactive Focus LC-MS/MS system delivers a versatile, high-performance solution for routine HRAM analysis. By combining proven Orbitrap technology with flexible acquisition modes and robust software workflows, it enables laboratories to achieve confident identification, precise quantitation, and efficient non-targeted screening in a single, cost-effective platform.

References

• Thermo Fisher Scientific. Q Exactive Focus Hybrid Quadrupole-Orbitrap LC-MS/MS System Brochure. 2016.
• Thermo Fisher Scientific. Quick and Sensitive Analysis of Multiclass Veterinary Drug Residues in Meat, Plasma, and Milk on a Q Exactive Focus LC-MS System. Application Note AN64249-EN.
• Thermo Fisher Scientific. Quantitation of Opiates to Low ng/mL Levels in Urine for Forensic Use Using an Affordable, High-Resolution, Accurate-Mass Mass Spectrometer. Application Note AN64257-EN.
• Thermo Fisher Scientific. Quick and Sensitive Analysis of Pesticides Using a Full-Scan Data-Dependent MS/MS Approach on a Q Exactive Focus LC-MS System. Application Note AN64284-EN.
• Thermo Fisher Scientific. Quantification of Steroids in Human Plasma by Liquid Chromatography Coupled with the Affordable Q Exactive Focus HRMS. Application Note AN64333-EN.