The bi-directional β-radiation MCC/IMS operated with synthetic air under ambient pressure and temperature used for the study was custom designed at ISAS and has been described in detail in literature as well as the software used for data acquisition and evaluation [6–8]. For pre-separation, a 20 cm un-polar multi-capillary chromatographic column (OV-5, MULTICHROM, Novosibirsk, Russia) was operated isothermal at 40 °C. Sampling was controlled by a CO2 sensor (IRMA, Fa. PhaseIn, Danderyd, Sweden), which was used to flush the sample loop (8 mL volume) only if carbon dioxide exceeded 25 mmHg, thus sampling only end-tidal breath. The volume of the sample loop was then introduced directly into the MCC without any pre-treatment of the sample.
Propofol (2,6-diisopropylphenol) is characterised by a molecular mass of 178 u and a phenolic chemical structure. Propofol and Thymol (used as internal standard) for calibration were obtained from Sigma–Aldrich (Seelze, Germany). A calibration gas generator (HovaCAL 3834SC VOC, Inspire Analytical Systems GmbH, Frankfurt am Main, Germany, see ) was used for calibration of MCC/IMS. The generator provided Propofol concentrations (1, 3, 5, 7, 9 and 10 ppbv) in humid air (100% relative humidity at 37 °C). The calibration results (correlation coefficient of 0.984, n= 24) are presented in Fig. 1. The Propofol concentration could be determined by the MCC/IMS in breath with a mean standard deviation of 2.5% and by GC/MS in serum with 12.2%.
Thirteen patients scheduled for an elective ear–nose–throat surgery procedure (nine male, four female, all classified as American Society of Anaesthetist physical status I or II, see ) were involved in the study. In the mean, patients were 45 years of age and their body-mass-index (BMI) was 24.6 (Table 1). The study was approved by the ethics committee of the University of Göttingen, Germany (protocol No. 01/07/08). All patients gave written informed consent to participate in the investigation.
Anaesthesia and sample acquisition
The patients received a standard total intravenous anaesthesia (TIVA) with Propofol (Disoprivan 1%; Astra Zeneca, Wedel, Germany) as hypnotic agent, Remifentanil for analgesia and optional Rocuronium as muscle relaxant. Anaesthesia was induced with intravenous application of 2.1 (±0.7) mg/kg Propofol bolus and 30 μg/kg/h Remifentanil. After tracheal intubation, the lung was ventilated with a standard anaesthesia respirator (Cato, Dräger, Lübeck, Germany). Propofol (3.9 (±1.8) mg/kg/h) and Remifentanil (30 μg/kg/h) were applied continuously to maintain anaesthesia adjusted to clinical parameters. Sampling was performed as described above and in Total Intravenous Anaesthesia in analogy to Schubert et al.  measuring CO2 in breath with mainstream capnography (IRMA, Fa. PhaseIn, Danderyd, Sweden). Breath samples were drawn when the CO2 level exceeded 25 mmHg and venous blood samples were obtained via a separate venous access at the opposite site of the drug infusion simultaneously. All samples were collected at steady state conditions (achieved by administration of Propofol and Remifentanil for 15 min). Depending on the duration of surgery, one or two sample pairs of breath and serum were taken per patient.
Determination of propofol concentrations by GC/MS
Breath samples have been adsorbed on Tenax tubes (1 L of breath, controlled by the sampling control of the MCC/IMS) and were thermally desorbed and analysed just as the blood samples (injected in one bolus at 250 °C) using a GC/MS with EI-ionisation (70 eV) by Agilent Technologies 6,890 N GC-system connected to an Agilent Technologies 5,973 mass selective detector (MSD; Gerstel, Mülheim, Germany). The operating parameters were: SSL-injector 180 °C; column DB-5: 30 m; 0,25 mm ID; 0,25 μm FD; 1 mL/min He const.; T-program 40 °C/5 °C/min–100 °C/20 °C/min–200 °C (5 min). Integrated signals from the internal standard Thymol (m/z 135,150) and from Propofol (m/z 163,178) were evaluated by AMDIS/NIST (Automated Mass Spectral Deconvolution and Identification System; version 2.62, 2005; NIST version 2.0, 2005).
Simultaneously to breath sampling, venous blood was from the arm that was not used for the infusion. All samples were collected under steady-state conditions (Achieved by administration of Propofol and Remifentanil for 15 min). Depending on the duration of surgery, 1–2 samples were obtained from each patient.