title: 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.
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai 201203, China.
authors.forename: Chunyong
authors.initials: C
authors.lastname: He
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai 201203, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Thermo Fisher Scientific, Chromatography and Mass spectrometry Division, Shanghai 201206, China.
authors.forename: Niusheng
authors.initials: N
authors.lastname: Xu
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai 201203, China.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Wang
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zeyun
authors.initials: Z
authors.lastname: Li
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai 201203, China. Electronic address: yangli7951@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai 201203, China. Electronic address: ztwang@shutcm.edu.cn.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D036145:Ginsenosides / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D036145:Ginsenosides; C000603656:notoginsenoside Fc
keywords: Bioavailability; LC–MS/MS; Metabolism; Notoginsenoside Fc; Pharmacokinetics