title: Excretion of berberine and its metabolites in oral administration in rats.
abstract: Berberine (BBR) has been confirmed to show extensive bioactivities for the treatments of diabetes and hypercholesterolemia in clinic. However, there are few pharmacokinetic studies to elucidate the excretions of BBR and its metabolites. Our research studied the excretions of BBR and its metabolites in rats after oral administration (200 mg/kg). Metabolites in bile, urine, and feces were detected by liquid chromatography coupled to ion trap time-of-flight mass spectrometry; meanwhile, a validated liquid chromatography coupled with tandem mass spectrometry method was developed for their quantifications. Sixteen metabolites, including 10 Phase I and six Phase II metabolites were identified and clarified after dosing in vivo. Total recovered rate of BBR was 22.83% (19.07% of prototype and 3.76% of its metabolites) with 9.2 × 10(-6) % in bile (24 h), 0.0939% in urine (48 h), and 22.74% in feces (48 h), respectively. 83% of BBR was excreted as thalifendine (M1) from bile, whereas thalifendine (M1) and berberrubine (M2) were the major metabolites occupying 78% of urine excretion. Most of BBR and its metabolites were found in feces containing 84% of prototype. In summary, we provided excretion profiles of BBR and its metabolites after oral administration in rats in vivo.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Ma
authors.forename: Ru
authors.initials: R
authors.lastname: Feng
authors.forename: Xiang-Shan
authors.initials: XS
authors.lastname: Tan
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Jia-Wen
authors.initials: JW
authors.lastname: Shou
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: He
authors.forename: Shuo-Nan
authors.initials: SN
authors.lastname: Chen
authors.forename: Zhen-Xiong
authors.initials: ZX
authors.lastname: Zhao
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000652:urine; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005243:Feces / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D001599:Berberine; C115958:berberrubine; C477156:thalifendine
keywords: analytical chemistry; berberine; excretion; mass spectrometry; metabolism; pharmacokinetics