Integration of Ultra-short Chain PFAS Into Routine Analysis Methods: Addressing Retention and Confirmatory Ions

Significance of the Topic

Per- and polyfluoroalkyl substances (PFAS) are increasingly regulated due to their persistence and health risks. As long-chain PFAS (≥C8) are phased out, short-chain (C4–C7) and ultra-short (

Study Objectives and Overview

This work aims to integrate ultra-short chain PFAS into a single LC-MS/MS method by combining a mixed-mode chromatographic column with enhanced low-mass transmission on a tandem quadrupole mass spectrometer. Key targets include improving retention of compounds like trifluoroacetic acid (TFA) and perfluoropropionic acid (PFPrA) and establishing a confirmatory ion (m/z 19) for analytes historically lacking one.

Methodology

Water samples (5 mL) from surface and wastewater sources were prepared via ASTM 8421: dilution with methanol, syringe filtration, and pH adjustment to 4 using acetic acid. LC separation was performed on an Atlantis Premier BEH C18 AX column under a gradient of ammonium acetate in water and methanol with ammonium hydroxide. MS detection used a Xevo TQ Absolute mass spectrometer in ESI mode, with automated low-mass (≤50 Da) transmission settings for the m/z 19 fragment.

Instrumentation

• LC System: ACQUITY Premier with PFAS Kit and Atlantis Premier BEH C18 AX columns (2.1 × 50 mm, 5 µm; 2.1 × 100 mm, 1.7 µm)
• MS System: Xevo TQ Absolute, ESI source, waters_connect software, capillary voltage 0.5 kV, desolvation 350 °C, cone gas 150 L/h

Main Results and Discussion

Mixed-mode chromatography provided strong retention of TFA and PFPrA, preventing early elution in the void volume and improving peak shape. Adjusting sample pH to 4 stabilized retention times across matrices. Enhancing low-mass transmission on the Xevo TQ Absolute dramatically increased response for the m/z 19 fragment. This allowed use of m/z 19 as a confirmatory ion for PFBA and PFPeA over a wide calibration range (1–1 000 ng/L) with stable ion ratios within ±30%. In landfill leachate, C4–C14 PFAS were quantified and confirmed in one injection, with percent differences below 15% versus reverse-phase results.

Benefits and Practical Applications

• Single-injection analysis of ultra-short to long-chain PFAS streamlines workflow
• Mixed-mode column eliminates co-elution of early eluting acids
• m/z 19 fragment provides a reliable confirmatory ion for C2–C4 PFAS
• Method compatible with existing LC-MS/MS platforms, removing need for additional columns or HRMS

Future Trends and Opportunities

Further advancements may include exploration of alternative mixed-mode chemistries targeting emerging PFAS classes, automated on-line sample preparation for high throughput, and integration with machine-learning algorithms for non-target screening. Expanding the confirmatory ion library and refining low-mass MS settings will support regulatory compliance and broader environmental surveillance.

Conclusion

The combination of a mixed-mode BEH C18 AX column and enhanced low-mass transmission on a Xevo TQ Absolute enables robust retention and confirmation of ultra-short chain PFAS. This integrated approach broadens analytical coverage from C2 to C14 PFAS in a single LC-MS/MS run, improving confidence in environmental monitoring.