Pharmacokinetic and Relative Bioavailability of Three Secoiridoid Glycosides in Beagle Dog Plasma After Oral Administration of Conventional and Enteric-Coated Capsules of Gentianella acuta Extract

摘要

Objective: To simultaneously investigate the pharmacokinetics of gentiopicroside, sweroside, and swertiamarin, which are constituents of Gentianella acuta, by developing and validating a simple, sensitive, and fast ultra-high-performance liquid chromatography–tandem mass spectrometry method. Materials and Methods: Blood samples were collected from the forward limb veins of six beagle dogs following oral gavage with G. acuta, the whole plant extract（39.90 mg/kg）. Plasma samples were processed using liquid–liquid extraction. The analytes and paeoniflorin（internal standard [IS]） were separated using an Acquity? UPLC ethylene bridged hybrid amide column（2.1 mm × 100 mm, 1.7 μm） with isocratic elution using a mobile phase consisting of acetonitrile and 0.1% formic acid in water（80:20, v/v） at a flow rate of 0.4 mL/min. Quantification was performed using multiple reaction monitoring of the fragmentation transitions at m/z 401.1→179.0, 403.1→195.0, 419.1→179.0, and 525.2→449.1 for gentiopicroside, sweroside, swertiamarin, and the IS, respectively. Results: The linearity of the analytical response was good and the calibration curves were linear over concentration ranges of 1.20–192.0, 0.40–159.0, and 0.20–209.3 ng/mL for gentiopicroside, sweroside, and swertiamarin, respectively. The extraction recovery was in the range of 84.72%–91.34%, 84.58%–93.43%, and 82.75%–91.37% for gentiopicroside, sweroside, and swertiamarin, respectively. Conclusions: The method was successfully used to evaluate the pharmacokinetic parameters of gentiopicroside, sweroside, and swertiamarin in beagle dogs.