Quantification of Per- and Polyfluoroalkyl Substances in Drinking Water

Significance of the Topic

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that pose significant human health risks when present in drinking water at trace levels. Reliable, sensitive analytical methods are essential for regulatory compliance and public safety. High-resolution accurate-mass (HRAM) instrumentation, such as quadrupole time-of-flight (Q-TOF) mass spectrometers, offers both targeted quantification and the ability to screen for unknown PFAS, making it a powerful tool for comprehensive water quality monitoring.

Objectives and Study Overview

This study demonstrates the adaptation of U.S. EPA Method 533—originally designed for triple quadrupole LC/MS—to an Agilent 6546 LC/Q-TOF system. The primary goals are to:

• Validate that the Q-TOF meets all sensitivity and performance criteria defined in EPA Method 533.
• Compare method reporting levels (LCMRLs) and precision with established LC/TQ benchmarks.
• Highlight the added benefit of non-targeted screening for emerging PFAS compounds.

Applied Methodology and Instrumentation

Sample preparation followed EPA Method 533 guidelines: 250 mL drinking water samples were fortified with isotope-dilution standards, extracted via weak anion exchange SPE, eluted with ammonium hydroxide/methanol, dried, and reconstituted in 80% methanol.

The chromatographic system comprised an Agilent 1290 Infinity II LC with a delay column (4.6 × 50 mm C18) to remove background PFAS, and an analytical ZORBAX RRHD Eclipse Plus C18 column (3 × 50 mm, 1.8 µm) at 50 °C, using a water/ammonium acetate–methanol gradient at 0.4 mL/min. Injection volume was 10 µL.

The Agilent 6546 LC/Q-TOF operated in electrospray negative mode with Targeted MS/MS isolation of precursor ions within narrow retention windows. Key parameters included:

• Source: dual Agilent Jet Stream ESI, 230 °C gas temperature, 4 L/min gas flow, 375 °C sheath gas.
• MS/MS: 5 spectra/s acquisition rate, fragmentor 95 V, skimmer 65 V, collision energies optimized per compound.

Data were processed with Agilent MassHunter Quantitative Analysis (v10.1) and Qualitative Analysis (v10.0) software.

Main Results and Discussion

Chromatographic separation achieved baseline resolution of PFAS acids (retention times ~4–9 min) and sulfonates/fluorotelomer sulfonates (9–17 min). Calibration used quadratic fits with 1/x weighting, forcing the origin, yielding R² values >0.98 (most >0.995) and sub-2 ppm mass accuracy for product ions.

Precision was excellent: relative standard deviations (n=9) were below 12% for all 25 target compounds (majority <5%), surpassing the 20% requirement. Estimated LCMRLs ranged from 0.01 to 5.93 ng/L—well below EPA’s reported thresholds for 21 of 25 analytes. The delay column effectively eliminated background PFAS peaks at target retention times.

Untargeted full-scan data acquired at 50 Hz enabled retrospective screening: at mid-calibrator levels (25 ng/L), 92% of all compounds were identified with mass-match scores >80%; at the lowest calibrator (1.6 ng/L), 17 of 25 compounds still exceeded 80% match.

Benefits and Practical Applications

The Agilent 6546 LC/Q-TOF system meets or exceeds EPA Method 533 requirements for PFAS quantitation in drinking water, offering:

• High sensitivity and precision comparable to LC/TQ instruments.
• Simultaneous targeted quantitation and untargeted screening for emerging contaminants.
• Simplified method transfer with minimal changes to extraction and chromatography protocols.

These capabilities support environmental laboratories, regulatory agencies, and industrial QA/QC processes.

Future Trends and Opportunities

HRAM Q-TOF platforms will increasingly enable:

• Expanded suspect and non-target screening libraries for novel PFAS.
• Retrospective data mining as new analytes of concern are identified.
• Integration with machine learning tools for automated formula assignment and trend analysis.
• Streamlined workflows combining quantitative and qualitative PFAS assessments.

Conclusion

The Agilent 6546 LC/Q-TOF, when configured for Targeted MS/MS acquisition, fully satisfies EPA Method 533 criteria for PFAS analysis in drinking water. It delivers robust precision, low detection limits, and the added value of high-resolution full-scan data for comprehensive monitoring of known and emerging PFAS compounds.