UC Irvine

Trifluoroacetic acid (TFA) is an ultrashort-chain per- and polyfluoroalkyl substance (PFAS) that is small in molecular size, with strong acidity, high water solubility, and low hydrophobicity. These properties contribute to high environmental mobility and substantial analytical challenges. Other than direct environmental release, TFA also serves as the degradation endpoint for various anthropogenic precursors, such as fluorinated refrigerants, pesticides, pharmaceuticals, and industrial chemicals. Conventional reversed-phase chromatography PFAS methods provide insufficient TFA retention because its small size, high polarity, negative charge, and low hydrophobicity limit interaction with C18 phases. This poor retention can cause early elution with matrix constituents and greater sensitivity to background contamination from various laboratory materials such as storage tubing and instrumentation used during dilution. Hydrophilic column chemistries, such as hydrophilic interaction liquid chromatography (HILIC), can improve the retention of highly polar compounds like TFA and help overcome limitations associated with conventional reversed-phase PFAS separations. HILIC columns overcome some of these limitations by providing greater retention of highly polar analytes through partitioning into a water-rich layer on the polar stationary phase, along with additional polar and ionic interactions that can improve separation from early-eluting matrix components.This study developed and evaluated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining TFA, using laboratory-prepared aqueous samples as a foundation for future application to environmental surface water. The analysis was performed on an Agilent 6470 triple-quadrupole mass spectrometer operated in negative electrospray ionization mode with an Agilent AdvanceBio HILIC column. Method development evaluated chromatographic retention, mobile-phase conditions, injection parameters, multiple-reaction-monitoring conditions, dwell time, calibration strategy, and control of laboratory background. The final TFA acquisition method monitored the transition m/z 113 → 69 with a 100 ms dwell time, and TFA eluted at approximately 2.20 min. Calibration standards from 75 to 300 ng/L produced a concentration-dependent response, with a 1/x-weighted linear calibration yielding an R² of 0.9972. Blank responses were more than two orders of magnitude lower than the lowest calibration standard. Preliminary calculations based on calibration slope and blank variability produced estimated detection and quantitation limits of approximately 0.42 and 1.27 ng/L. However, this was not confirmed with low-concentration validation samples.The results show the feasibility of the developed HILIC LC-MS/MS approach for TFA measurement under controlled laboratory conditions. Formal assessment of accuracy, precision, low-level quantitative performance, matrix effects, and performance in surface water remains crucial before the method can be considered validated for environmental monitoring.