POPS: Quantitative comparison of perfluorinated alkyl substances in drinking water between tandem triple quadrupole MS/MS and high resolution mass spectrometry using orbitrap technology – knowns and unknowns

Significance of the Topic

Perfluorinated alkyl substances (PFAS) are persistent environmental pollutants frequently detected in drinking water. Accurate quantification and identification of both regulated and emerging PFAS is critical for health risk assessment, regulatory compliance, and remediation efforts.

Objectives and Study Overview

This study compares quantitative analysis of PFAS in drinking water using tandem triple quadrupole mass spectrometry (MS/MS) and high resolution Orbitrap mass spectrometry. It evaluates known targets under EPA Method 537 and explores non-targeted screening of unknown PFAS compounds.

Methodology

• Sample preparation: SPE extraction of 250 mL water samples with Trizma buffer and surrogate standards, followed by methanol elution and concentration.
• Chromatography: UHPLC separation on C18 column with a methanol–water gradient.
• Mass spectrometry: Comparison of triple quadrupole SRM, Orbitrap PRM, and full-scan HRAM at 70 000–140 000 resolution.
• Quantitation: Internal standard calibration, LCMRL calculation, and surrogate recovery monitoring.
• Data mining: Compound Discoverer software for formula prediction and isotopic pattern matching.

Instrumentation Used

• Thermo Q-Exactive Orbitrap mass spectrometer with electrospray ionization.
• Triple quadrupole MS/MS system for SRM mode.
• Online SPE UHPLC system for combined targeted and non-target screening.

Main Results and Discussion

• Orbitrap PRM achieved quantitation comparable to triple quadrupole SRM, with similar sensitivity and enhanced specificity.
• Full-scan HRAM provided more reliable quantitation of branched PFOS isomers, overcoming response factor variability.
• Detection limits for key PFAS were below 0.5 ppt, meeting or exceeding EPA 537 requirements.
• Simultaneous targeted and non-targeted analyses enabled discovery of additional PFAS species, including PFBA, PFDS, and novel suspects.
• High resolution and accurate mass data facilitated confident formula assignment and isotopic pattern confirmation.

Benefits and Practical Applications

• Consolidation of routine quantitation and non-target screening into a single analysis streamlines laboratory workflows.
• Enhanced selectivity reduces interferences and lowers false positives in complex matrices.
• Comprehensive data enables monitoring of regulated PFAS and emerging contaminants with minimal method development.

Future Trends and Applications

Integration of full-scan HRAM with targeted PRM workflows is expected to expand non-targeted PFAS discovery, supported by evolving data analysis tools. Ongoing development of suspect libraries and advanced structural confirmation techniques (e.g., MSⁿ, NMR) will further enhance the characterization of novel PFAS.

Conclusion

• High resolution Orbitrap PRM matches triple quadrupole SRM performance while offering improved specificity.
• Full-scan HRAM is superior for quantifying branched PFAS isomers.
• Combined targeted and non-targeted approaches provide comprehensive PFAS profiling in a single run.
• Advanced software tools are essential for efficient data processing and suspect identification.

References

• Peterson, A. C., Russell, J. D., Bailey, D. J., Westphall, M. S., & Coon, J. J. (2012). Parallel reaction monitoring for high resolution and high mass accuracy quantitative targeted proteomics. Molecular & Cellular Proteomics, O112.020131.
• Riddell, N., et al. (2009). Characterization of branched isomers of PFOS by tandem mass spectrometry relative response factors.