title: Simultaneous determination of four furostanol glycosides in rat plasma by UPLC-MS/MS and its application to PK study after oral administration of Dioscorea nipponica extracts.
abstract: A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for simultaneous quantification of four furostanol glycosides in rat plasma was established and validated. Ginsenoside Rb1 was used as an internal standard. Plasma samples were pretreated by liquid-liquid extraction with n-butanol and chromatographed on a C18 column (2.1×50 mm i.d., 2.6 μm) using a gradient elution program consisting of acetonitrile and water (containing 0.03% formic acid and 0.1 mM lithium acetate) at a flow rate of 0.4 mL/min. Lithium adduct ions were employed to enhance the response of the analytes in electrospray positive ionization mode and multiple reaction monitoring transitions were performed for detection. All calibration curves exhibited good linearity (r>0.999) over the range of 10-20,000 ng/mL for protodioscin and 2-4000 ng/mL for protogracillin, pseudoprotodioscin and pseudoprotogracillin. The recoveries of the whole analytes were more than 80.3% and exhibited no severe matrix effect. Meanwhile, the intra- and inter-day precisions were all less than 10.7% and accuracies were within the range of -8.1-12.9%. The four saponins showed rapid excretion and relative high plasma concentrations when the validated method was applied to the PK study of Dioscorea nipponica extracts by intragastric administration at low, medium and high dose to rats. Moreover, the T(1/2) and AUC(0-t) of each compound turned out to behave in a dose-dependent pattern by comparing them at different dose levels.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Dai
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Mengping
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Jiefeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Zuanguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: yaomeicun@gmail.com.
authors.forename: Meicun
authors.initials: M
authors.lastname: Yao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D027742:Dioscorea; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D006027:Glycosides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013261:Sterols / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004365:Drugs, Chinese Herbal; D006027:Glycosides; D013261:Sterols; C574436:furostanol glycoside
keywords: Dioscorea nipponica; Furostanol glycosides; Lithium adduct; Pharmacokinetics; Rat plasma; UPLC–MS/MS