Studies pertaining to the monitoring of volatile halogenated anaesthetics in breath by proton transfer reaction mass spectrometry.

Post-operative isoflurane has been observed to be present in the end-tidal breath of patients who have undergone major surgery, for several weeks after the surgical procedures. A major new non-controlled, non-randomized, and open-label approved study will recruit patients undergoing various surgeries under different inhalation anaesthetics, with two key objectives, namely (1) to record the washout characteristics following surgery, and (2) to investigate the influence of a patient's health and the duration and type of surgery on elimination. In preparation for this breath study using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), it is important to identify first the analytical product ions that need to be monitored and under what operating conditions. In this first paper of this new research programme, we present extensive PTR-TOF-MS studies of three major anaesthetics used worldwide, desflurane (CF3CHFOCHF2), sevoflurane ((CF3)2CHOCH2F), and isoflurane (CF3CHClOCHF2) and a fourth one, which is used less extensively, enflurane (CHF2OCF2CHFCl), but is of interest because it is an isomer of isoflurane. Product ions are identified as a function of reduced electric field (E/N) over the range of approximately 80 Td to 210 Td, and the effects of operating the drift tube under 'normal' or 'humid' conditions on the intensities of the product ions are presented. To aid in the analyses, density functional theory (DFT) calculations of the proton affinities and the gas-phase basicities of the anaesthetics have been determined. Calculated energies for the ion-molecule reaction pathways leading to key product ions, identified as ideal for monitoring the inhalation anaesthetics in breath with a high sensitivity and selectivity, are also presented.

Proton transfer reaction time-of-flight mass spectrometric measurements of volatile compounds contained in peppermint oil capsules of relevance to real-time pharmacokinetic breath studies.

With the growing interest in the use of breath volatiles in the health sciences, the lack of standardization for the sampling and analysis of exhaled breath is becoming a major issue leading to an absence of conformity, reproducibility and reliability in spectrometric measurements. Through the creation of a worldwide 'peppermint consortium', the International Association of Breath Research has set up a task force to deal with this problem. Pharmacokinetic studies are proposed, and a real-time analytical technique that is being used is proton transfer reaction-time-of-flight-mass spectrometry (PTR-ToF-MS). This paper presents details on how the volatile compounds contained in a peppermint oil capsule, and hence on breath, appear in a PTR-ToF-MS. To aid that study, the key volatiles in the headspace of peppermint oil were first identified using gas chromatography-mass spectrometry, notably: menthol, menthone, 1,8-cineole, menthofuran, limonene, α-pinene and ß-pinene. A PTR-ToF-MS analysis of these compounds has been undertaken, divorced from the complexity of the peppermint oil matrix using 'normal' and 'saturated' humidity drift-tube conditions, with the latter used to mimic breath samples, and over a range of reduced electric fields. There are no characteristic product ions that can distinguish monoterpenes and 1,8-cineole, and hence, without pre-separation, a combined washout for these volatiles can only be provided. By operating the drift tube above about 130 Td, there are characteristic product ions for menthone, menthofuran and menthol, namely m/z 155.14 (protonated menthone), m/z 151.11 (protonated menthofuran), m/z 139.15 (loss of H2O from protonated menthol) and m/z 83.09 (a fragment ion, C6H11 +, from menthol). These have been used to monitor, with a high specificity, the temporal profile of these three compounds in breath following the ingestion of a peppermint oil capsule. To aid in the analyses, the proton affinities and gas-phase basicities for the key volatiles investigated have been determined using density functional theory.