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

J Pharm Biomed Anal. 2021 Jan 30:193:113714. doi: 10.1016/j.jpba.2020.113714. Epub 2020 Oct 20.

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.

Keywords: Atmospheric-pressure chemical ionization (APCI); C18 pipette-tip; Mass spectrometry; Pharmacokinetics; Propofol; Solid-phase extraction (SPE).

MeSH terms

  • Atmospheric Pressure
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Humans
  • Propofol*
  • Reproducibility of Results
  • Solid Phase Extraction
  • Tandem Mass Spectrometry*

Substances

  • Propofol