HPLC-MS/MS determination and pharmacokinetic study of propofol in human plasma

Objective:To develop a rapid,simple and sensitive high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for the quantitative determination and pharmacokinetic study of propofol in human plasma.Methods:Separation was performed on a Zorbax Eclipse XDB-C18 column column(50 mm×4.6 mm,5 μm)with gradient elution at a flow rate of 0.3 mL·min-1.The mobile phase was 0.1% aqueous ammonium hydroxide and methanol.Detection was performed in a triple-quadruple tandem mass spectrometer by multiple-reaction-monitoring mode via electrospray ionization.Results: Linear calibration curve was obtained in the concentration range of 0.010-12 μg·mL-1(r≥0.99),with a lower limit of quantification of 0.010 μg·mL-1.The intra-and inter-day precision(RSD)values were below 15% and accuracy(RE)ranged from-2.0% to 5.0% at all QC levels.A three-compartment pharmacokinetic model best described the pharmacokinetics of propofol.Clearance was 0.029 L·min-1·kg-1,the volume of distribution of the central compartment was 0.60 L·kg-1,elimination half-life t1/2α was 0.84 min,t1/2β was 6.7 min and t1/2γ was 128.7 min.Conclusion: A rapid,accurate and sensitive method was developed and successfully applied to the pharmacokinetic study of propofol in healthy Chinese volunteers following intravenous administration.