Validation of liquid and gaseous calibration techniques for quantification of propofol in breath with sorbent tube Thermal Desorption System GC-MS

Plasma concentrations of intravenous drugs cannot currently be evaluated in real time to guide clinical dosing. However, a system for estimating plasma concentration of the anesthetic propofol from exhaled breath may soon be available. Developing reliable calibration and analytical validation techniques is thus necessary. We therefore compared the established sorbent tube liquid injection technique with a gas injection procedure using a reference gas generator. We then quantified propofol with Tenax sorbent tubes in combination with gas-chromatography coupled mass spectrometry in the breath of 15 patients (101 measurements). Over the clinically relevant concentration range from 10 to 50 ppbv, coefficient of determination was 0.995 for gas calibration; and over the range from 10 to 100 ng, coefficient of determination was 0.996 for liquid calibration. A regression comparing gas to liquid calibration had a coefficient of determination of 0.89; slope 1.05 ± 0.01 (standard deviation). The limit of detection was 0.74 ng and the lower limit of quantification was 1.12 ng for liquid; the limit of detection was 0.90 ppbv and the lower limit of quantification was 1.36 ppbv for gas. Loaded sorbent tubes were stable for at least 14 days without significant propofol loss as determined with either method. Measurements from liquid or gas samples were comparably suitable for evaluation of patient breath samples.