Determination and pharmacokinetic study of chiisanogenin in rat plasma by ultra performance liquid chromatography‐tandem mass spectrometry

Abstract

Chiisanogenin existing in many Acanthopanax species has been reported to possess anti-inflammatory, antibacterial and antiplatelet aggregatory activities. To develop and validate a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method for the determination of chiisanogenin in rat plasma and to investigate its pharmacokinetics after oral administration of chiisanogenin or the extract of Acanthopanax sessiliflorus fruits. The sample pretreatment involved a one-step extraction of 0.2 mL plasma with diethyl ether. Acetaminophen was used as the internal standard. The separation was carried out on an ACQUITY UPLC™ BEH C₁₈ column with a mobile phase of acetonitrile-5 mM ammonium acetate (90:10, v/v) at a flow rate of 0.2 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. A high sample throughput was achieved with an analysis time of 1.1 min per sample. The calibration curve was linear (r² ≥ 0.99) over the concentration range of 5-500 ng/mL with a lower limit of quantification (LLOQ) of 5 ng/mL. The intra-day and inter-day precision (relative standard deviation, R.S.D.) values were below 11% and the accuracy (relative error, R.E.) was within 8% at all three quality control (QC) levels. The method was successfully applied to the pharmacokinetic study of chiisanogenin in rat after oral administration of chiisanogenin and the extract of Acanthopanax sessiliflorus fruits. Other constituents in the extract affected the pharmacokinetic behavior of chiisanogenin.