title: Simultaneous quantification of twenty-one ginsenosides and their three aglycones in rat plasma by a developed UFLC-MS/MS assay: Application to a pharmacokinetic study of red ginseng.
abstract: To track the pharmacokinetic features of red ginseng (RG), a rapid and sensitive ultra fast liquid chromatographic coupled with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous quantification of twenty-one ginsenosides and their three aglycones, including 18 prototype compounds (ginsenosides Rb1, Rb2, Rc, Rd, Re, Rg1, Rg5, Rh4, Rk1, Rk3, 20(S)-Rf, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(R)-Rh1, 20(S)-NG-R2), and 6 metabolites (ginsenosides 20(S)-Rh2and Rh3, 20(S)-protopanaxadiol (PPD), 20(S)-protopanaxatriol (PPT), 20(R)-PPT, ginseng saponin compound K) of RG in rat plasma after oral administration of RG water extract at a single dose of 4g/kg body weight to rats. All analytes with internal standard (digoxin) were detected by multiple reaction monitoring in negative ionization mode and separated on an ACQUITY UPLC®BEH RP-C18column (1.7μm, 100×2.1mm). This established method was well validated in terms of linearity, sensitivity, intra- and inter-day precisions, accuracy, recovery, matrix effect, stability, and had a lower limit of quantification at the concentration range of 0.12-8.12ng/mL for all of analytes. This UFLC-MS/MS approach was successfully applied to the pharmacokinetic study for RG water extract in rats. We firstly proposed that Rb1, Rb2, Rc, Rd, Rg1, Rg5, 20(S)-Rg3, 20(S)-Rh2, and 20(S)-PPD measured in rat plasma were suitable pharmacokinetic markers of RG extract in rats due to their high systemic exposure levels. Thus, this specific and reliable method will be useful for future applications to pharmacokinetic studies for various sources of ginsenoside samples and Panax herbs in vivo.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Qi-Le
authors.initials: QL
authors.lastname: Zhou
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100088, China; College of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: Di-Na
authors.initials: DN
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: xwyang@bjmu.edu.cn.
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Yang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics; D036145:Ginsenosides / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D005894:Panax / Q000737:chemistry*; D010949:Plasma / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D012503:Saponins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D012502:Sapogenins; D012503:Saponins; C081552:protopanaxatriol; C062916:protopanaxadiol
keywords: Ginsenoside; Pharmacokinetics; Rat plasma; Red ginseng; UFLC–MS/MS