title: Stereoselective pharmacokinetic and metabolism studies of 20(S)- and 20(R)-ginsenoside Rg₃ epimers in rat plasma by liquid chromatography-electrospray ionization mass spectrometry.
abstract: 20(S)- and 20(R)-ginsenoside Rg3 are a pair of epimers which could be deglycosylated to ginsenoside Rh2 and protopanaxadiol (PPD) in vivo. To better understand the differences of pharmacokinetic parameters and metabolism behaviors of Rg3 epimers in rat plasma, a sensitive and specific liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and fully validated. This chromatographic method separate 20(S)-/20(R)-Rg3, 20(S)-/20(R)-Rh2 and 20(S)-/20(R)-PPD by gradient elution of 10 mM ammonium acetate solution (pH 5.0) and acetonitrile on a C18 column with a total run time of 15 min. 20(S)-protopanaxatriol (PPT) was used as internal standard, and multiple reaction monitoring (MRM) mode with negative electrospray ionization were performed. The lower limit of quantitations (LLOQs) were between 4.2 and 4.8 ng/ml, and the accuracies were between 91.7% and 112.2% with intra- and inter-day precisions less than 11.6%. This method was successfully applied to a pharmacokinetic study of intravenous and intra-gastric administration of 20(S)-Rg3 and 20(R)-Rg3 to rats. It has been found that both epimers can be deglycosylated to their corresponding chiral metabolites, i.e., Rh2 and PPD, with different extents. However, 20(R)-Rg3 underwent single direction chiral inversion to 20(S)-Rg3 in rats. Stereoselective pharmacokinetic parameters, metabolic degrees and chiral inversion extents of Rg3 epimers in rats were also discussed for the first time.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China; Department of Chemistry, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Peng
authors.affiliation: College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Li
authors.affiliation: Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China. Electronic address: zhangtongshutcm@hotmail.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ding
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Department of Chemistry, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Le
authors.affiliation: Department of Chemistry, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D036145:Ginsenosides / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D010949:Plasma / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D036145:Ginsenosides; D012502:Sapogenins; C097367:ginsenoside Rg3; C081552:protopanaxatriol; C055305:ginsenoside Rh2; C062916:protopanaxadiol
keywords: Chiral inversion; Ginsenoside Rg(3); LC–MS/MS; Pharmacokinetics; Rat metabolism; Stereoselective