title: Pharmacokinetic studies of novel berberine derivatives with ultra-performance liquid chromatography-tandem mass spectrometry.
abstract: An ultra-performance liquid chromatography with tandem mass spectrometric detection method was developed for the detection of berberine and its derivatives (A4, B4) in rat plasma and other organs. This validated method was successfully applied to our pharmacokinetic study of BBR derivatives in rats. At the same dose of administration, the Cmax of B4 was about eight times higher than BBR, and its half-life was approximately two times longer than BBR, according to the bigger areas under plasma concentration curves. Inversely, the pharmacokinetic parameter levels of A4 were all inferior to BBR, suggesting a tight structure-activity relationship of these compounds. Small dose of parenteral administration was used for the study of absolute oral bioavailability of A4, B4, and BBR, and the results calculated were 0.12%, 3.4% and 0.7%, respectively. The accumulations of B4 among all organs were intestine>liver>heart>kidney>lung>spleen>plasma, proving a deeply targeting property of B4, which met our experimental assumption. Together, the experimental results proved that compared with BBR and A4, the derivative B4 had higher absolute oral bioavailability and the ability of deeply targeting so that can be likely used in some organ-targeted diseases.
authors: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310032, China.
authors: Wenchao
authors: W
authors: Wang
authors: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310032, China.
authors: Qin
authors: Q
authors: Shen
authors: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310032, China.
authors: Hui
authors: H
authors: Liang
authors: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310032, China.
authors: Changlong
authors: C
authors: Hua
authors: Department of Neurobiology, key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Provine Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310032, China.
authors: Yuhui
authors: Y
authors: Liu
authors: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute (RPCI), NY 14263, USA.
authors: Fengzhi
authors: F
authors: Li
authors: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: liqy@zjut.edu.cn.
authors: Qingyong
authors: Q
authors: Li
mesh_terms: D000818:Animals; D001599:Berberine / Q000097:blood / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D001599:Berberine
keywords: Berberine (BBR); Berberine derivatives; Pharmacokinetics; Targeting; Tissue distribution; UPLC–MS/MS