title: Simultaneous determination of three Panax notoginseng saponins at sub-nanograms by LC-MS/MS in dog plasma for pharmacokinetics of compound Danshen tablets.
abstract: Compound Danshen tablets are composed of Panax notoginseng, Salvia miltiorrhiza and Borneol. The tablets are prescribed for treatment of cardiovascular diseases in China. The present study aimed at developing a specific and sensitive LC-MS/MS method to simultaneously determine three bioactive P. notoginseng saponins, i.e., notoginsenoside R1, ginsenoside Rg1 and Rb1, in dogs after a single oral administration of the compound tablets in order to obtain the clinically relevant saponin-related pharmacodynamics of the tablets in patients. The R1, Rg1 and Rb1 were extracted from dog plasma with acetone-methanol (80:20, v/v), separated by reversed phase liquid chromatography and determined by tandem mass spectrometry (LC-MS/MS) with positive electrospray ionization (ESI). The developed method reached lower limit of quantitation (LLOQ) at 0.10 ng/ml for the three saponins. The method was validated in terms of selectivity, matrix effects, linearity, precision and accuracy, and then was applied to a pharmacokinetic study of the three bioactive saponins simultaneously in dogs after a single oral administration of compound Danshen tablets at a clinical equivalent dose. The C(max) and AUC((0-∞)) for R1, Rg1 and Rb1 were 1.91, 3.34 and 28.6 ng/ml, and 7.5, 11.0, and 1712 (h ng/ml), respectively.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China. cqsongmin@yahoo.cn
authors.forename: Min
authors.initials: M
authors.lastname: Song
authors.forename: Siyun
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Taijun
authors.initials: T
authors.lastname: Hang
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D004285:Dogs / Q000097:blood*; D004355:Drug Stability; D036145:Ginsenosides / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D016014:Linear Models; D053723:Panax notoginseng / Q000737:chemistry*; D015203:Reproducibility of Results; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012680:Sensitivity and Specificity; D013607:Tablets; D053719:Tandem Mass Spectrometry
chemical_list: D036145:Ginsenosides; D013607:Tablets