Minimal retarded Propofol signals in human breath using ion mobility spectrometry

Abstract

Propofol is a short-acting, intravenously administered hypnotic agent. Since the introduction of propofol into clinical practice, it has become the intravenous induction agent of choice for anaesthesia providers (Fig. 1). The physicochemical properties of Propofol are given in Table 1. Currently, there are no simple, reliable and clinically useful measures available to quantify Propofol in humans at the bedside. For investigations in pharmacokinetics and dynamics Propofol is measured in serum samples, which are invasive, time-consuming and therefore results are not directly available. The level of Propofol in the exhaled air can potentially be used as an indicator of patients’ hypnotic depth and would provide the possibility to measure the Propofol concentration on-line. Generally, several methods are under investigation to monitor the concentration of Propofol in exhaled breath. For example, mass spectrometry with emphasis on proton transfer reaction mass spectrometry, ion-molecule reaction mass spectrometry or GC/MS have been described [1–7]. The detection of Propofol in exhaled air using ion mobility spectrometry coupled to multi-capillary (MCC) columns was shown most recently [8–11]. The MCC provides the possibility to work within humid environment. The reactant ion peak (RIP) is clearly separated from the peak of Propofol using MCC combined with an IMS. The identification uses the drift time of the ions formed from Propofol and the retention time within the MCC. The signal intensity can be related to the concentration range with relevance for clinical diagnostics[8] . Further details with respect to the advantages and disadvantages of MCC [12–17] and the IMS [18–25] are well known. With respect to the detection of Propofol, a retention time of about 10 min was realized keeping the MCC adjusted at 40 °C. Perl et al. [9] estimated, that at higher MCC temperatures, retention times in the range of 1 min could be achieved. Zhou et al. [26] used a membrane inlet system for on-line measurement of Propofol in an anesthetized mouse and showed direct Propofol concentration in a time series. In their mouse model, the time profile showed a gap of about 10 min before the Propofol signal was observable. A close relation to serum Propofol concentration in air was found using mass spectrometric methods [4, 7]. Recently, a strong correlation between the serum Propofol concentration and signal intensity of ion mobility spectrometry has also been shown [8, 9, 11]. The goal of the present pilot is to show that by modifying the MCC/IMS peak of Propofol values can be obtained online within 60 s. To demonstrate biologically meaningful variations the MCC/IMS was applied in a conventional operation room. The peak intensities delivered by BioScout could then directly be correlated to the BIS-values of brain activity, where Propofol is expected to have its major effects in vivo.