Dose‐dependent exposure profile and metabolic characterization of notoginsenoside R 1 1 in rat plasma by ultra‐fast liquid chromatography–electrospray ionization–tandem mass spectrometry

摘要

Abstract Notoginsenoside R 1 (NGR 1 ), a diagnostic protopanaxatriol‐type (ppt‐type) saponin in Panax notoginseng , possesses potent biological activities including antithrombotic, anti‐inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR 1 in rats after oral and intravenous administration and to explore the metabolic characterization of NGR 1 . A simple and sensitive ultra‐fast liquid chromatographic–tandem mass spectrometric method was developed and validated for the quantitative determination of NGR 1 and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0?min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR 1 exhibited dose‐independent exposure behaviors with t 1/2 over 8.0?h and oral bioavailability of 0.25–0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20( R )‐notoginsenoside R 2 /20( S )‐notoginsenoside R 2 and 20( R )‐ginsenoside Rh 1 /20( S )‐ginsenoside Rh 1 , with the 20( R ) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20( S )‐notoginsenoside R 2 , ginsenoside Rg 1 , ginsenoside F 1 and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.