Determination of Pseudoginsengenin DQ in rat plasma by UPLC–MS/MS and application of the method in a pharmacokinetic study

Pseudoginsengenin DQ (pseudoginsengenin of diol derivatives quest, PDQ), the product of the oxidative cyclization of protopanaxadiol, exhibits a significant pharmacological effect as an antiarrhythmic agent. A sensitive and rapid analytical method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS) was initially developed for the detection of PDQ in rat plasma. Pre-treatment of the sample obtained from the plasma involved a single protein precipitation step, using methanol. PDQ and an internal standard (IS), physcion, were separated on a Waters ACQUITY UPLC BEH C18 analytical column (50 mm × 2.1 mm, 1.7 μm) using acetonitrile-0.1% formic acid in water (70:30, v/v) as the mobile phase, at a flow rate of 0.3 mL/min. Chromatography of the PDQ and IS was performed within 3 min. Detection was performed through positive ion electrospray ionization (ESI+) in multiple reaction-monitoring (MRM) mode. The assay was linear over the concentration range of 5–1000 ng/mL (r > 0.9980). The limit of detection (LOD) and the lower limit of quantification (LLOQ) were 0.5 ng/mL and 5.0 ng/mL, respectively. The intra- and inter-day deviations (expressed as relative standard deviation, RSD) were ≤9.5% and ≤1.7%, respectively, and the accuracy (expressed as relative error, RE) was in the range of −1.1 to 2.7%. The recoveries of PDQ and IS were 95.2% and 100.7%, respectively, and the matrix effects were satisfactory in all of the biological matrices examined. This fully validated method was successfully applied to the pharmacokinetic study of rats after a single initial intragastric administration of 15 mg/kg PDQ. The main pharmacokinetic parameters: Tmax (the time to peak), Cmax (the concentration to peak), and t1/2 (the biological half time) were 4.0 ± 0.0 h, 3265.12 ± 700.26 ng/mL, 5.97 ± 0.43 h, respectively.