Abstract
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 (50mm×2.1mm, 1.7μm) using acetonitrile-0.1% formic acid in water (70:30, v/v) as the mobile phase, at a flow rate of 0.3mL/min. Chromatography of the PDQ and IS was performed within 3min. Detection was performed through positive ion electrospray ionization (ESI(+)) in multiple reaction-monitoring (MRM) mode. The assay was linear over the concentration range of 5-1000ng/mL (r>0.9980). The limit of detection (LOD) and the lower limit of quantification (LLOQ) were 0.5ng/mL and 5.0ng/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 15mg/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±0.0h, 3265.12±700.26ng/mL, 5.97±0.43h, respectively.
Published Version
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