Pharmacokinetics, bioavailability, and metabolism of Notoginsenoside Fc in rats by liquid chromatography/electrospray ionization tandem mass spectrometry

Abstract

Notoginsenoside Fc (NGFc) is a protopanaxadiol-type (PPD-type) saponin from Panax notoginseng, which has perfect anti-platelet aggregatory effect. However, its pharmacokinetics and metabolism in vivo remain unknown. In this study, a simple and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC–MS/MS) method was first developed for the determination of NGFc in rat plasma. After methanol-mediated protein precipitation, separation was achieved on a C18 column with MS detection operated in negative SRM mode at m/z 604.56→m/z 783.90 and m/z 799.93→m/z 637.64 for NGFc and IS, respectively. The assay was linear over the concentration range (r>0.995) with the LLOQ of 0.002μg/ml. The intra- and inter-day precisions (R.S.D.) were 2.45–12.36% and 3.67–14.22%, respectively; whereas accuracy ranged from (R.R.) 93.90% to 99.41%. The extraction recovery, stability, and matrix effect were within the acceptable limits. The validated LC–MS/MS method was successfully applied to the pre-clinical pharmacokinetic studies of NGFc in rat. After oral and intravenous administration, NGFc showed dose-independent pharmacokinetic behaviors with a t1/2 of >22h and its oral bioavailability was 0.10–0.14%. In addition, a total of 10 metabolites were detected and structurally characterized by UPLC–Q/TOF-MS technique, which suggested that deglycosylation was the major metabolic pathway for NGFc in rats.