Comprehensive Non-Targeted PFAS Analysis Using Quadrupole Time-of-Flight (QToF) Mass Spectrometry with a Multi-Approach Data Processing Workflow

Importance of the Topic

PFAS are persistent, highly stable compounds with significant environmental and health concerns. Traditional targeted LC-MS/MS methods may overlook unknown or emerging PFAS. Non-targeted high-resolution mass spectrometry enables broad detection and structural elucidation of diverse PFAS chemotypes.

Study Objectives and Overview

This work aimed to develop and validate a comprehensive non-targeted PFAS screening workflow using QToF mass spectrometry. The method was tested in the 2024 NIST interlaboratory study on three unknown environmental samples to benchmark performance against established criteria.

Methodology and Instrumentation

• Samples: Three NIST-provided unknown extracts (A, B, C)
• Liquid Chromatography: C18 reversed-phase column, binary gradient of 2 mM ammonium acetate and acetonitrile, 30-min run
• Mass Spectrometry: Shimadzu LCMS-9050 QToF, data-dependent acquisition in positive and negative ion modes
• Data Processing: LabSolutions Insight Explore, FluoroMatch, and custom C++ scripts; NIST SQLite library conversion to .mlb format
• Identification Criteria: MS1/MS2 matching, m/z error <5 ppm, isotope pattern verification, retention time, and neutral loss screening

Main Results and Discussion

The workflow identified 49, 101, and 134 PFAS in samples A, B, and C, respectively, with negative ion mode yielding higher hit rates. Integration of NIST suspect lists, library matches, and FluoroMatch scoring achieved 100 % coverage of target compounds in the interlaboratory study for this laboratory (DIM003). Rigorous peak quality checks minimized false positives and ensured confident annotation.

Benefits and Practical Applications

• Unbiased detection of known and emerging PFAS structures
• Comprehensive isomer and homolog series profiling
• Enhanced identification confidence via multi-criteria scoring
• Applicability to environmental monitoring, regulatory compliance, and remediation assessment

Future Trends and Applications

Advancements may include artificial intelligence–driven spectral annotation, expanded and community-curated PFAS libraries, integration of ion mobility separation, and real-time field-deployable HRMS platforms. Collaborative data sharing will further accelerate discovery of novel PFAS entities.

Conclusion

This study demonstrates a robust, multi-approach QToF workflow for non-targeted PFAS analysis, achieving comprehensive coverage and high confidence in identification. It establishes a benchmark for future environmental analytical protocols.

Used Instrumentation

• Shimadzu LCMS-9050 Quadrupole Time-of-Flight Mass Spectrometer
• C18 reversed-phase liquid chromatography column
• LabSolutions Insight Explore software
• FluoroMatch software
• Custom C++ data processing tools

References

1. Place B, Reiner J, Ragland J, et al. Per- and Polyfluoroalkyl Substances – Non-Targeted Analysis Interlaboratory Study Final Report, NISTIR. National Institute of Standards and Technology; 2024. doi:10.6028/NIST.IR.8544
2. Charbonnet JA, McDonough CA, Xiao F, et al. Communicating Confidence of PFAS Identification via High-Resolution Mass Spectrometry. Environmental Science & Technology Letters. 2022;9(6):473-481. doi:10.1021/acs.estlett.2c00206