Sensitive Perfluoroalkyl Substance (PFAS) Screening Using High Resolution Accurate Mass Spectral Library

Importance of the Topic

Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants found in many consumer and industrial products and are linked to adverse health effects. Sensitive detection and accurate identification of PFAS at trace levels are critical for environmental monitoring, regulatory compliance and risk assessment.

Study Objectives and Overview

This study aimed to develop a highly sensitive liquid chromatography–quadrupole time-of-flight (LC-QTOF) method, complemented by a high-resolution accurate mass spectral library, to improve PFAS screening performance. The approach focused on enhancing detection confidence, reducing false positives and false negatives, and achieving reliable quantitation across complex matrices.

Methodology and Instrumentation

An advanced QTOF mass spectrometer (LCMS-9030) with electrospray ionization was optimized for PFAS analysis. Chromatographic separation was performed on a Restek Raptor C18 column using a Nexera-X2 UHPLC system. Accurate mass spectral library entries were generated by injecting pure standards and validated against the EPA’s DSSTox database and formula prediction software. Standard EPA Method 537.1 served as a reference for compound selection and method criteria.

Used Instrumentation

• UHPLC System: Shimadzu Nexera-X2
• Column: Restek Raptor C18, 150×2.1 mm, 2.7 µm
• Mass Spectrometer: Shimadzu LCMS-9030 QTOF
• Ion Source: Electrospray Ionization (ESI)
• MS Scan Range: 100–800 m/z

Main Results and Discussion

• Mass Accuracy Stability: The QTOF exhibited stable mass accuracy over three days without recalibration, with mass errors consistently within ±2 ppm for all target PFAS.
• Quantitative Performance: Calibration curves showed r2 > 0.99. LLOQ repeatability at 5 ng/L met acceptance criteria for most compounds. Mid-range precision at 25 ng/L yielded recoveries between 70–130% and relative standard deviations below 15% for the majority of analytes.
• Isomer Resolution: The high-resolution method differentiated linear and branched isomers of PFHxS and PFOS, supported by library matching scores above 90.
• Library Matching: Accurate MS and MS/MS spectral matching reduced false identifications in complex samples, with library similarity scores typically above 75.

Benefits and Practical Applications

• Enhanced detection confidence through accurate mass library matching.
• Comparable quantitative capabilities to triple quadrupole MS methods.
• Reduced risk of false positives and false negatives in environmental and biological matrices.
• Ability to screen a broad range of PFAS compounds in a single run.

Future Trends and Potential Applications

The expansion of high-resolution spectral libraries, integration of retention time prediction, and non-targeted screening approaches will further strengthen PFAS analysis. Automation and data processing advancements will enable high-throughput environmental monitoring and regulatory compliance.

Conclusion

The developed LC-QTOF method with an accurate mass spectral library offers a robust and sensitive solution for PFAS screening. It delivers stable mass accuracy, reliable quantitation, and improved compound identification, making it suitable for complex sample analysis and regulatory applications.

Reference

• EPA Method 537.1
• EPA DSSTox and CompTox Databases