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

[Image: see text] 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 H(3)O(+), NO(+), and O(2)(+•) 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 H(3)O(+) and NO(+), but it does react efficiently with O(2)(+•) via dissociative charge transfer resulting in CHF(2)(+), CF(3)(+), C(2)HF(2)O(+), and C(2)H(2)F(3)O(+). A minor competing hydride abstraction channel results in C(3)HF(6)O(+) + HO(2)(•) and, following an elimination of HF, C(3)F(5)O(+). There are two issues associated with the use of the three dominant product ions of HFIP, CHF(2)(+), CF(3)(+), and C(2)H(2)F(3)O(+), to monitor it in breath. One is that CHF(2)(+) and CF(3)(+) also result from the reaction of O(2)(+•) 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, C(2)H(2)F(3)O(+) 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.