## 2 Materials and Methods
### Sample Preparation  
Given their low vapour pressure, reliable direct headspace measurements of propofol and 2,6-diisopropyl-1,4-benzoquinone are difficult. Therefore, we adopted a technique more suitable for the chemical analysis of compounds that are semi-volatiles at room temperature. A 1 L glass gas bulb (Supelco Analytical, PA, USA) was placed in an oven (Memmert GML, Innsbruck, Austria) at 60 \({}^{\circ}\)C. This bulb was evacuated using a vacuum pump (Vacuumbrand GmbH + Co KG, Wertheim, Germany) for about 30 min. Following this, 1 \(\upmu\)L of neat propofol or its metabolite was injected into the preheated and evacuated gas bulb through a septum. The gas bulb was then connected via a valve to a 3 L Tedlar gas bag (SKC Ltd., Dorset, UK) which was filled with high-purity nitrogen (99.9999%, <3 ppmv water). Once the valve was opened, the gas bulb was brought-up to atmospheric pressure. To limit condensation of the compounds, the gas bulb was maintained at 60 \({}^{\circ}\)C throughout the measurements. In order to obtain a constant compound volume mixing ratio (~600 ppbv) in the drift tube, 1.25 mL of the standard from the gas bulb was introduced into a 250 mL glass syringe filled with either dry (~0% relative humidity (rH)) or humid (~100% rH) high-purity nitrogen for the normal and humid drift tube condition measurements, respectively. The humid sample, which mimics breath samples, was only used for the propofol measurements and was achieved by bubbling the high-purity nitrogen through distilled water kept at room temperature. The 250 mL syringe was also held at 60 \({}^{\circ}\)C throughout the measurements. The Proton Transfer Reaction-Time-of-Flight-Mass Spectrometer/Selective Reagent Ionisation-Time-of-Flight-Mass Spectrometer  
The PTR/SRI-ToF-MS used in this study was a compact high-performance extended PTR-TOF 6000 X2 (Ionicon Analytik GmbH, Innsbruck, Austria) [24; 25; 26; 27] that has a high mass resolving power (m/\(\Delta\)m) of approximately 6000 at \(m/z\) 147, which provides high confidence in accurately identifying the product ions from the \(m/z\) values. Information on the operational procedures of PTR/SRI-ToF-MS is discussed in detail in the literature [28; 29]. In brief, the drift tube was maintained at a constant pressure of 2.6 mbar for H\({}_{3}\)O\({}^{+}\) and 2.3 mbar for O\({}_{2}{}^{+\bullet}\) and NO\({}^{+}\) using a dry or humid nitrogen carrier gas and at a temperature of 353 K. Owing to the fixed number density, \(N\), only the drift tube voltage needed to be varied to alter the value of the reduced electric field. By varying the applied drift voltage from about 220 V up to about 660 V, an \(E\)/\(N\) range of approximately 60-210 Td was covered. The reagent ions H\({}_{3}\)O\({}^{+}\) and H\({}_{3}\)O\({}^{+}\).H\({}_{2}\)O (PTR-mode) and NO\({}^{+}\) and O\({}_{2}{}^{+\bullet}\) (SRI-mode) investigated in this study were created in the hollow cathode ion source by introducing water vapour, a 3:1 mix of nitrogen (99.9999% purity) and medical grade oxygen (>99.5% purity), into the ion source, respectively. Figure 1 displays the signal intensities in counts per second (cps) for all reagent ions as a function of \(E\)/\(N\) ranging from about 60 Td up to about 210 Td in steps of 20 Td under both _normal_ and _humid_ drift tube conditions. In contrast to SIFT-MS, for which the reagent ion is actively selected [30], soft chemical ionisation mass spectrometric analytical instruments rely solely on ion chemistry to form the dominant reagent ion. As a consequence of this, impurity reagent ions are always present in the drift tube but generally in very low concentrations. The only exception is H\({}_{3}\)O\({}^{+}\).H\({}_{2}\)O, whose levels can be higher than those of H\({}_{3}\)O\({}^{+}\) depending on the \(E\)/\(N\) value applied and the humidity of the buffer gas within the drift tube. It is the responsibility of the experimentalist to ensure that the contributions of the impurity reagent ions to product ion formation are either negligible or properly accounted for.