DETERMINATION OF PLASMA PROPOFOL LEVELS USING GAS-CHROMATOGRAPHY MASS-SPECTROMETRY WITH SELECTED-ION MONITORING

Propofol (2,6-diisopropylphenol, I.C.I. 35 868) is a rapid-acting, int ravenous anesthetic agent recently introduced for the induction and ma intenance of general anesthesia. This paper describes a gas chromatogr aphic-mass spectrometric procedure using selected-ion monitoring for t he determination of plasma propofol levels. The drug and the internal standard (thymol) were extracted from plasma into diethyl ether-pentan e, and derivatized to their trimethylsilyl derivatives before analysis . The reproducibility of the daily standard curves had coefficients of variation ranging from 2.7% to 10.2%. The precision of the assay yiel ded a coefficient of variation ranging from 4.5% to 5.6%, and the conc entration means for the seeded control samples were found to be within -1.6% to +0.6% of the theoretical values for propofol. No interfering peaks have been observed in application of this procedure to either n ormal volunteer or patient samples. The minimum detectable level under the conditions described was 0.20 ng propofol/ml plasma. This assay a nd a high-performance liquid chromatographic assay with fluorescence d etection were both used to measure plasma propofol concentrations in 8 9 human plasma samples, and the correlation between the two methods wa s excellent.