As a part of an ongoing study to determine the concentrations of inhalation anaesthetics in the exhaled breath of patients following surgery, separate investigations are being undertaken to determine which soft chemical ionisation mass spectrometric techniques are most suitable for real-time breath measurements. Towards that goal, we present here details of a selective reagent ion-time-of-flight-mass spectrometer study investigating the reactions of O₂^+· with isoflurane, enflurane, desflurane, and sevoflurane. Information on the product ions as a function of reduced electric field and the influence of humidity in the drift (reaction) tube is presented. With increasing humidity in the drift tube, secondary product ion-water reactions lead to significant decreases in the intensities of many of the primary product ions, resulting here in a reduced analytical sensitivity for the four fluranes. However, for breath analysis this is found not to be a major issue owing to the high concentrations of inhalation anaesthetics found in exhaled breath even several days after surgery. This is demonstrated in a clinical measurement involving a patient who had undergone an operational procedure, with sevoflurane being used for maintenance of general anaesthesia. Graphical abstract

The first High Kinetic Energy-Ion Mobility Spectrometry-Mass Spectrometry (HiKE-IMS-MS) studies involving six volatiles (acetone, acetonitrile, methanol, ethanol, 2-propanol, and 1-butanol) and their fully deuterated analogues are reported. The goal is to further our understanding of the ion–molecule chemistry occurring in the HiKE-IMS. This is needed for its full analytical potential to be reached. Product ions are identified as a function of the reduced electric field (30–115 Td) and the influence of sample air humidity in the reaction region on deuterium/hydrogen (D/H) exchange reactions is discussed. Reagent ions include H₃O⁺(H₂O)_m (n = 0, 1, 2 or 3), NO⁺(H₂O)_n (m = 0 or 1) and O₂^+·. Reactions with H₃O⁺(H₂O)_m lead to protonated monomers (through either proton transfer or ligand switching). Reactions with NO⁺ involve association with acetone and acetonitrile, hydride anion abstraction from ethanol, 2-propanol, and 1-butanol, and hydroxide abstraction from 2-propanol and 1-butanol. With the exception of acetonitrile, O₂^+· predominantly reacts with the volatiles via dissociative charge transfer. A number of sequential secondary ion-volatile processes occur leading to the formation of dimer and trimer-containing ion species, whose intensities depend on a volatile’s concentration and the reduced electric field in the reaction region. Deuterium/hydrogen (D/H) exchange does not occur for product ions from acetone-d₆ and acetonitrile-d₃, owing to their inert methyl functional groups. For the deuterated alcohols, rapid D/H-exchange reaction at the hydroxy group is observed, the amount of which increased with the increasing humidity of the sample air and/or lowering of the reduced electric field. Graphical abstract

The first detailed selected reagent ion-time-of-flight-mass spectrometric fundamental investigations of 2,6-diisopropylphenol, more commonly known as propofol (C₁₂H₁₈O), and its metabolite 2,6-diisopropyl-1,4-benzoquinone (C₁₂H₁₆O₂) using the reagent ions H₃O⁺, H₃O⁺.H₂O, O₂^+• and NO⁺ are reported. Protonated propofol is the dominant product ion resulting from the reaction of H₃O⁺ with propofol up to a reduced electric field strength (E/N) of about 170 Td. After 170 Td, collision-induced dissociation leads to protonated 2-(1-methylethyl)-phenol (C₉H₁₃O⁺), resulting from the elimination of C₃H₆ from protonated propofol. A sequential loss of C₃H₆ from C₉H₁₃O⁺ also through collision-induced processes leads to protonated phenol (C₆H₇O⁺), which becomes the dominant ionic species at E/N values exceeding 170 Td. H₃O⁺.H₂O does not react with propofol via a proton transfer process. This is in agreement with our calculated proton affinity of propofol being 770 kJ mol⁻¹. Both O₂^+• and NO⁺ react with propofol via a charge transfer process leading to two product ions, C₁₂H₁₈O⁺ (resulting from non-dissociative charge transfer) and C₁₁H₁₅O⁺ that results from the elimination of one of the methyl groups from C₁₂H₁₈O⁺. This dissociative pathway is more pronounced for O₂^+• than for NO⁺ throughout the E/N range investigated (approximately 60–210 Td), which reflects the higher recombination energy of O₂^+• (12.07 eV) compared to that of NO⁺ (9.3 eV), and hence the higher internal energy deposited into the singly charged propofol. Of the four reagent ions investigated, only H₃O⁺ and H₃O⁺.H₂O react with 2,6-diisopropyl-1,4-benzoquinone, resulting in only the protonated parent at all E/N values investigated. The fundamental ion-molecule studies reported here provide underpinning information that is of use for the development of soft chemical ionisation mass spectrometric analytical techniques to monitor propofol and its major metabolite in the breath. The detection of propofol in breath has potential applications for determining propofol blood concentrations during surgery and for elucidating metabolic processes in real time.

Here, we present proof of principle studies to demonstrate how the product ions associated with the ion mobility peaks obtained from a High Kinetic Energy-Ion Mobility Spectrometer (HiKE-IMS) measurement of a volatile can be identified using a Proton Transfer Reaction/Selective Reagent Ion-Time-of-Flight-Mass Spectrometer (PTR/SRI-ToF-MS) when operating both instruments at the same reduced electric field value and similar humidities. This identification of product ions improves our understanding of the ion chemistry occurring in the ion source region of a HiKE-IMS. The combination of the two analytical techniques is needed, because in the HiKE-IMS three reagent ions (NO⁺, H₃O⁺ and O₂^+•) are present at the same time in high concentrations in the reaction region of the instrument for reduced electric fields of 100 Td and above. This means that even with a mass spectrometer coupled to the HiKE-IMS, the assignment of the product ions to a given reagent ion to a high level of confidence can be challenging. In this paper, we demonstrate an alternative approach using PTR/SRI-ToF-MS that allows separate investigations of the reactions of the reagent ions NO⁺, H₃O⁺ and O₂^+•. In this study, we apply this approach to four nitrile containing organic compounds, namely acetonitrile, 2-furonitrile, benzonitrile and acrylonitrile. Both the HiKE-IMS and the PTR/SRI-ToF-MS instruments were operated at a commonly used reduced electric field strength of 120 Td and with gas flows at the same humidities.