Differentiating PFAS Isomers: A Multi-Pass Cyclic Ion Mobility Mass Spectrometry Approach for Detection, Identification, and Relative Quantitation

Importance of the Topic

Per- and polyfluoroalkyl substances PFAS are widely employed industrially and remain pervasive in the environment. Their resilience and potential adverse health impacts heighten the need for precise detection. Commercial PFAS formulations often contain complex mixtures of linear and branched isomers whose different sources and behaviors necessitate detailed separation and analysis. Advanced profiling of these isomers enables more accurate contamination fingerprinting and supports improved regulatory monitoring.

Objectives and Study Overview

This study aimed to enhance separation, identification, and relative quantitation of PFAS isomers using a multi-pass cyclic ion mobility mass spectrometry approach coupled with liquid chromatography. Researchers examined both commercial technical standards of perfluorooctanesulfonic acid PFOS and perfluorooctanoic acid PFOA, alongside real-world drinking water samples. The goals included expanding the number of resolved isomers, comparing quantitation with established NMR methods, and exploring isomer distribution in environmental matrices.

Methodology

Liquid chromatography enabled initial retention-based separation using a C18 reverse-phase column with a gradient of water and methanol both containing ammonium acetate. Effluent was directed to a cyclic ion mobility spectrometry IMS cell allowing multiple passes to increase collision cross section resolution. Up to six passes were performed to distinguish closely related branched PFOS isomers and three passes for PFOA fragments. Drift-specific extracted ion chromatograms facilitated relative quantitation. Authentic standards and calculated collision cross section values supported structural assignments.

Used Instrumentation

• LC system: ACQUITY I-Class PLUS with PFAS kit, CORTECS Premier C18 column
• Mobile phases: water and methanol with 2 mM ammonium acetate
• Flow rate 0.3 mL/min, gradient duration 16 min, injection volume 5-10 µL
• MS platform: SELECT SERIES cyclic IMS QTOF, ESI in negative mode
• IMS settings: multi-pass cyclic path (3 to 6 cycles), ion trap fragmentation for PFOA
• Mass range m/z 50–1200, resolution ~60000 FWHM at MS stage
• Data processing: waters_connect software within UNIFI application

Main Results and Discussion

Combining LC with multi-pass IMS enabled detection of 18 structural PFOS isomers in the technical standard, exceeding previously reported counts. Six-cycle IMS separation resolved most single-branched isomers; additional targeted selection further distinguished closely eluting species. Quantitation of isomer abundances correlated well with 19F NMR reference data. Analysis of drinking water samples revealed unique PFOS isomer profiles, indicating variable source contributions. PFOA isomer fragments were successfully separated after directed fragmentation and three-cycle IMS, highlighting the method’s versatility for different PFAS classes.

Benefits and Practical Applications

• Improved isomer resolution supports forensic source tracing and contamination fingerprinting.
• Relative quantitation aligns with established NMR methods, providing confidence in IMS-MS results.
• High-throughput screening of environmental samples becomes feasible with enhanced selectivity.
• Method extends to both sulfonic and carboxylic PFAS, broadening applicability in regulatory and industrial settings.

Future Trends and Opportunities

Further developments may integrate automated multi-pass IMS workflows for routine environmental monitoring. Expanded libraries of collision cross sections and authentic isomer standards will strengthen identification confidence. Coupling IMS with high-resolution fragmentation and machine learning algorithms could enable rapid pattern recognition of PFAS sources. Emerging cyclic IMS platforms may achieve even higher resolution with minimal sample preparation, opening avenues for in vivo and real-time exposure studies.

Conclusion

The multi-pass cyclic IMS-MS approach coupled with liquid chromatography significantly advances the separation, identification, and quantitation of PFAS isomers. Detecting previously unreported PFOS isomers and mapping unique isomer distributions in drinking water underscores the method’s power for environmental forensics. Strong agreement with NMR quantitation and adaptability to different PFAS classes suggest this technique as a valuable tool in analytical laboratories focused on environmental and public health assessments.

References

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• Greaves AK Letcher RJ 2013 Chemosphere 93 574-580
• McCullagh M et al 2021 Talanta 234 122604
• Dodds JN et al 2020 Analytical Chemistry 92 4427-4435
• Riddell N et al 2009 Org Halogen Compounds 70 001322