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

Abstract

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.

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

“…Humidity-dependent measurements are important because of potential secondary reactions of volatile’s primary product ions with any water vapor present in the drift tube of the PTR/SRI-ToF-MS. These secondary reactions were found to be significant for the primary ions produced from the reactions of both H 3 O + and O 2 +• with sevoflurane (and other fluranes) − and agree with an earlier selected ion flow tube-mass spectrometry (SIFT-MS) investigation of sevoflurane by Wang et al Similar problems with the product ions resulting from HFIP may also occur, which, if they do, would significantly diminish their concentrations and in turn reduce the PTR/SRI-ToF-MS’s analytical sensitivity for monitoring HFIP in exhaled breath.…”

“…Although there have been a number of soft chemical ionization mass spectrometric studies of volatile anesthetics in terms of fundamental ion molecule chemistry processes − , and for exhaled breath analysis, − ,− to our knowledge, none has investigated any associated volatile metabolites in any detail. In this study, we have investigated the chemical ionization of the metabolite of the inhalation anesthetic sevoflurane, namely HFIP with H 3 O + , NO + , and O 2 +• , as the reagent ions.…”

“…This type of product ion intensity behavior has been observed before in other PTR/SRI-ToF-MS studies when the primary product ions resulting from a compound react with water that is present in the drift tube. 5,6,18,37 Although we operated the drift tube under what is defined as dry conditions to record the data represented in Figure 1a, water vapor is always present in the drift tube, as is apparent from reagent ions H 3 O + and H 3 O + •H 2 O being observed. Even when using dry nitrogen carrier gas, there is sufficient water in the drift tube for the product ions signals to be reduced (see section 3.4.2 below).…”

Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD

“…PTR-MS and SESI-MS can be, and have been, used offline to analyse breath samples, but they come into their own for online analysis. However, the advantages of real-time analysis, which allows rapid changes in volatile concentrations to be detected, comes at the expense of identifying the volatiles with a high level of confidence [ 96 , 97 , 98 , 99 ]. Nevertheless, the near patient analyses mean that samples do not need to be transported and hence storage is not necessary.…”

4.2 - Compact Electrospray Ionization Ion Mobility Spectrometer

“…Furthermore, a variety of other applications exist, e.g. breath analysis [11], further medical applications [12,13] and environmental analysis [14].…”