title: Development and validation of an UFLC-MS/MS assay for the absolute quantitation of nine notoginsenosides in rat plasma: Application to the pharmacokinetic study of Panax Notoginseng Extract.
abstract: Notoginsenosides, the main active gradients of Chinese traditional medicine Panax notoginseng, possesses a variety of biological activities including antioxidant property, anti-hyperglycemic, anti-obese, etc. However, pharmacokinetic evaluation for notoginsenosides is still a formidable task due to their low concentrations and complex components in vivo. The summation of this work generated a rapid and sensitive method for quantitative analysis of multi-notoginsenoside in rat plasma based on ultra fast liquid chromatographic-tandem mass spectrometric. After liquid-liquid extraction by n-butanol, notoginsenoside R1, Rg3, Rd, Rg2, Rb2, Rf, Rg1, Rb1 and Re were simultaneously monitored in negative ionization mode after separating on a Thermo ODS C18 column (5mm 50mm×2.1mm) by a binary gradient elution, and all compounds were analyzed within 9min. Multiple reaction monitoring (MRM) was performed as follows: R1 (m/z 967.7→637.4), Rg3 (m/z 819.6→621.4), Rd (m/z 981.6→783.5), Rg2 (m/z 819.6→475.4), Rb2 (m/z 1113.4→783.4), Rf (m/z 835.6→475.4), Rg1 (m/z 835.6→637.6), Rb1 (m/z 1143.7→945.6), Re (m/z 981.6→637.4), internal standard (digoxin, m/z 815.5→779.4). Validation parameters (linearity, sensitivity, intra-and inter-assay precision and accuracy, recovery and matrix effect) were within acceptable ranges and biological extracts were stable during the entire storing and preparing process. This UFLC-MS/MS approach was further validated by being applied to the pharmacokinetic study for P. Notoginseng extract in rats, and the pharmacokinetic parameters were calculated by Winolin software. Thus, the presently developed methodology was simple, robust, accurate, precise, and would be useful for the pharmacokinetic studies for all kinds of notoginsenosides and other herbal saponins.
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China; Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xing
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Tai
authors.initials: T
authors.lastname: Rao
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Hanxu
authors.initials: H
authors.lastname: Fu
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China; Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China; Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China; Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Dian
authors.initials: D
authors.lastname: Kang
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China. Electronic address: liangyan0679@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics; D036145:Ginsenosides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; C519374:Panax notoginseng extract
keywords: Notoginsenosides; Panax Notoginseng extract; Pharmacokinetics; UFLC–MS/MS