Determination of propofol in human plasma with C18 pipette-tip based solid-phase extraction followed by liquid chromatography atmospheric-pressure chemical ionization tandem mass spectrometry analysis

Abstract Propofol is a widely used intravenous anesthetic for sedation during the surgery and worldwide propofol abuse has been frequently reported also. As an essential procedure for sample pretreatment, solid-phase extraction (SPE) is generally time-consuming and labor-intensive, which hindered the further improvement in the analysis of propofol from biological fluids. In this study, a rapid C18 pipette-tip based SPE method was developed to pretreat human plasma samples directly, bypassing the need for protein precipitation. The experiment conditions were optimized for the best extraction recovery (23.6 ± 4.1%). After pretreatment, the plasma propofol was determined with liquid chromatography atmospheric-pressure chemical ionization-tandem mass spectrometry (LC-APCI-MS/MS) using propofol-d17 as the internal standard. The quantification method showed good linearity in the range of 0.005 - 5 μg mL−1 ( r2 = 0.9992). The sensitivity, specificity, accuracy (90.0 - 113.3%), precision (2.0 - 8.9%), and stability (95.6 - 102.1%) were satisfied for bioanalytical analysis. Finally, the concentrations of propofol in the plasma of a patient under anesthesia were determined with the proposed method and compared with the theoretical concentrations calculated with a population pharmacokinetics (popPK) model. In general, this work provided a rapid and straightforward method for the study of propofol in pharmacokinetics and forensic science.