title: Pharmacokinetic study of five ginsenosides using a sensitive and rapid liquid chromatography-tandem mass spectrometry method following single and multiple oral administration of Shexiang Baoxin pills to rats.
abstract: Shexiang Baoxin pills (SBP) are a traditional Chinese medicine that are used for treating coronary heart disease. Ginsenosides are the main effective components of SBP, but a comprehensive and deep pharmacokinetic study of ginsenosides in SBP, including multiple dosing and linear or nonlinear properties, is lacking. This study was designed to investigate and compare the pharmacokinetic characteristics of ginsenosides in SBP at a single dose and in multiple doses. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of the ginsenosides Rg1, Re, Rb3, Rc and Rb1 in rat plasma. Rats were randomly assigned to receive a single dose of 4, 8 or 12 g/kg and multiple doses (4 g/kg) of SBP for 8, 15 or 22 consecutive days. The results revealed that ginsenosides, following a single oral dose of 4 or 8 g/kg, were absorbed rapidly, with a Tmax ranging from 0.250 to 1.08 h. The AUC0-t and Cmax of the ppd-type ginsenosides Rb3, Rc and Rb1 were greater than those of the ppt-type ginsenosides Rg1 and Re. Nondose-dependent exposure was observed at doses of 4-12 g/kg for all of the ginsenosides. After multiple dosing, the plasma levels of the ppt-type ginsenosides decreased, whereas those of the ppd-type ginsenosides did not change significantly. In conclusion, the LC-MS/MS method was successfully applied to investigate the pharmacokinetics of ginsenosides after single and multiple oral administrations of SBP. The ginsenosides did not accumulate after multiple dosing. The ppd-type ginsenosides displayed more favorable pharmacokinetic properties compared with the ppt-type ginsenosides.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Peng
authors.forename: Yongge
authors.initials: Y
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.forename: Huizi
authors.initials: H
authors.lastname: Jin
authors.forename: Jianfei
authors.initials: J
authors.lastname: Tao
authors.forename: Xing
authors.initials: X
authors.lastname: Yuan
authors.forename: Huimei
authors.initials: H
authors.lastname: Huang
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.forename: Wanlin
authors.initials: W
authors.lastname: Chang
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D004334:Drug Administration Schedule; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D036145:Ginsenosides / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; 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; C526712:shexiang baoxin
keywords: LC-MS/MS; Shexiang Baoxin Pills; ginsenosides; pharmacokinetic study