Orbitrap quantitation: lab of the future - Close your uncertainty gap with the selectivity and confidence of HRAM

Importance of topic

A high-resolution accurate-mass quantitation platform integrates qualitative and quantitative analysis in a single workflow. This capability addresses key challenges in food safety, environmental monitoring, clinical research, forensic toxicology, and pharmaceutical discovery by improving selectivity, sensitivity, and throughput while reducing method development time and the risk of false results.

Objectives and overview

This study presents the Thermo Scientific Q Exactive series of quadrupole–Orbitrap mass spectrometers as a solution for modern analytical laboratories. The goal is to demonstrate quantitative performance comparable to traditional triple quadrupole instruments and to highlight advantages in dynamic range, resolution, and comprehensive data collection for target and non-target compounds.

Methodology and instrumentation

The Q Exactive workflow combines liquid chromatography with high-resolution accurate-mass (HRAM) detection. Key components include:

• Heated electrospray ion source and RF lens for efficient ion transmission
• Hyperbolic quadrupole for mass selection down to 0.4 amu
• C-Trap and nitrogen-filled HCD cell for ion storage and fragmentation
• Orbitrap analyzer delivering resolving power up to 140 000 (FWHM) at m/z 200 and sub-ppm mass accuracy
• Multiple scan modes: full-scan MS, all-ion fragmentation (AIF), selected ion monitoring (SIM), parallel reaction monitoring (PRM), and data-independent acquisition (DIA)

Main results and discussion

Across diverse applications, the Q Exactive platform achieved:

• Up to six orders of linear dynamic range for small molecules such as Sunitinib
• Five orders of intra-scan dynamic range for accurate quantitation of high- and low-abundance species
• Resolution superior to Q-TOF systems, enabling separation of isobaric interferences at low levels
• Quantitation of hundreds of pesticides, veterinary drugs, mycotoxins, and environmental contaminants at low ng/L or ng/kg levels using simple workflows without extensive parameter optimization
• High-throughput screening in food safety and environmental testing, with retrospective data mining for unexpected analytes

Benefits and practical applications

Major advantages for routine laboratories include:

• Easier method development with no need to optimize dozens of SRM transitions
• Comprehensive quantitation of target and non-target compounds in one run
• Retrospective data analysis capability reducing the need for re-runs
• Improved confidence in results via high selectivity and accurate mass measurements
• Compatibility with fast chromatography and automated sample preparation for high sample throughput

Future trends and potential applications

Emerging directions include wider adoption of DIA workflows for non-target screening, integration of HRAM quantitation in metabolomics and lipidomics studies, real-time monitoring in clinical diagnostics, and further miniaturization of instruments. Combined with advanced data processing algorithms, HRAM platforms are poised to transform laboratory operations and decision making.

Conclusion

Quadrupole–Orbitrap mass spectrometer technology closes the uncertainty gap by delivering high-resolution quantitative and qualitative data in a single platform. Its broad dynamic range, superior selectivity, and flexible scan modes make it the lab of the future for food safety, environmental analysis, clinical research, forensic toxicology, and pharmaceutical discovery.

References

• Rajski L et al Large pesticide multiresidue screening by LC-Orbitrap in full-scan mode J Chromatogr A 1360 119–27 (2014)
• Wang J et al Determination of 166 pesticides in fruits and vegetables by UHPLC-Orbitrap HRMS J Agric Food Chem 60 12088–104 (2012)
• Gómez-Ramos MM et al LC-Orbitrap full-scan and MS/MS for selective pesticide analysis Anal Bioanal Chem 407 6317–26 (2015)