Detecting Hexafluoroisopropanol Using Soft Chemical Ionization Mass Spectrometry and Analytical Applications to Exhaled Breath

Here we explore the potential use of proton transfer reaction/selective reagent ion-time-of-flight-mass spectrometry (PTR/SRI-ToF-MS) to monitor hexafluoroisopropanol (HFIP) in breath. Investigations of the reagent ions H₃O⁺, NO⁺, and O₂^+• are reported using dry (relative humidity (rH) ≈ 0%) and humid (rH ≈ 100%)) nitrogen gas containing traces of HFIP, i.e., divorced from the complex chemical environment of exhaled breath. HFIP shows no observable reaction with H₃O⁺ and NO⁺, but it does react efficiently with O₂^+• via dissociative charge transfer resulting in CHF₂⁺, CF₃⁺, C₂HF₂O⁺, and C₂H₂F₃O⁺. A minor competing hydride abstraction channel results in C₃HF₆O⁺ + HO₂^• and, following an elimination of HF, C₃F₅O⁺. There are two issues associated with the use of the three dominant product ions of HFIP, CHF₂⁺, CF₃⁺, and C₂H₂F₃O⁺, to monitor it in breath. One is that CHF₂⁺ and CF₃⁺ also result from the reaction of O₂^+• with the more abundant sevoflurane. The second is the facile reaction of these product ions with water, which reduces analytical sensitivity to detect HFIP in humid breath. To overcome the first issue, C₂H₂F₃O⁺ is the ion marker for HFIP. The second issue is surmounted by using a Nafion tube to reduce the breath sample's humidity prior to its introduction into drift tube. The success of this approach is illustrated by comparing the product ion signals either in dry or humid nitrogen gas flows and with or without the use of the Nafion tube, and practically from the analysis of a postoperative exhaled breath sample from a patient volunteer.