BACKGROUND: Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical methods and robust correlations between drug concentrations in breath and blood can be established. We therefore applied headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to assess breath and blood concentrations of the intravenous drug propofol in patients under anesthesia or sedation. METHODS: Arterial, central- and peripheral-venous blood and alveolar breath samples were drawn in parallel from 16 mechanically ventilated patients. In addition, six patients undergoing lung resection were investigated. Substances were preconcentrated by means of HS-SPME, separated by GC and identified by MS. RESULTS: Propofol detection limits were 0.006 nmol/L in breath and 72.20 nmol/L in blood, the quantitation limits were 0.009 nmol/L and 75.89 nmol/L (end tidal breath/blood). Intraday precision was 8-11%, recovery 97-103%. Propofol concentrations were 0.04-0.5 nmol/L in breath and 2-120 micromol/L in blood. Only arterial propofol concentrations showed a correlation with concentrations in breath. Impaired ventilation/perfusion ratios in patients under lung resection resulted in changes of correlation coefficients. CONCLUSIONS: Reliable and precise analytical methods such as HS-SPME-GC-MS represent basic requirements if breath analysis is to be set up for non-invasive monitoring of intravenous drugs and control of anesthesia.
BACKGROUND:Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical methods and robust correlations between drug concentrations in breath and blood can be established. We therefore applied headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to assess breath and blood concentrations of the intravenous drug propofol in patients under anesthesia or sedation. METHODS: Arterial, central- and peripheral-venous blood and alveolar breath samples were drawn in parallel from 16 mechanically ventilated patients. In addition, six patients undergoing lung resection were investigated. Substances were preconcentrated by means of HS-SPME, separated by GC and identified by MS. RESULTS:Propofol detection limits were 0.006 nmol/L in breath and 72.20 nmol/L in blood, the quantitation limits were 0.009 nmol/L and 75.89 nmol/L (end tidal breath/blood). Intraday precision was 8-11%, recovery 97-103%. Propofol concentrations were 0.04-0.5 nmol/L in breath and 2-120 micromol/L in blood. Only arterial propofol concentrations showed a correlation with concentrations in breath. Impaired ventilation/perfusion ratios in patients under lung resection resulted in changes of correlation coefficients. CONCLUSIONS: Reliable and precise analytical methods such as HS-SPME-GC-MS represent basic requirements if breath analysis is to be set up for non-invasive monitoring of intravenous drugs and control of anesthesia.