title: Pharmacokinetics, excretion of 8-cetylberberine and its main metabolites in rat urine.
abstract: Berberine (BBR) is a bioactive plant ingredient derived from the roots and bark of Berberis aristata and Coptis chinensis and has a wide variety of pharmacological effects. 8-cetylberberine (8-BBR-C16) is the berberine (BBR) derivative reconstructed from adding octadecyl at C-8 of BBR to enhance its activity. This study presents a reliable method for the determination of BBR and 8-BBR-C16 in rat plasma, urine and feces. BBR and 8-BBR-C16 were determined by HPLC-UV after liquid-liquid extraction for plasma samples, and solid-phase extraction for urinary and fecal samples. The method was linear over the concentration range of 10-300 ng·ml-1for the plasma samples, 25-2000 ng·ml-1for the urinary samples, and 100-2000 ng·g-1for the fecal samples. Furthermore, a metabolic investigation on urine was performed by LC/MS/MS analysis to identify the structures of 8-BBR-C16 metabolites by full scan and product ion scan. Adult Sprague-Dawley rats were divided into two groups. In the control group, rats received 80 mg·kg-1BBR, and in the drug-treated group, rats received 80 mg·kg-18-BBR-C16. The results indicate that there were significant differences in the pharmacokinetic parameters and in the accumulated excretion levels between the control group and the drug-treated group. The Cmaxand AUC0-tof 8-BBR-C16 were 2.8 and 12.9 times higher than those of BBR, and the relative bioavailability of BBR to 8-BBR-C16 was 7.7%. The total excretion amount through the urine and feces of 8-BBR-C16 was 76.9%, but that of BBR was only 20.5%. Additionally, 8-BBR-C16 was metabolized in rat urine with phase I demethylation and phase II glucuronidation or sulfation.
authors.affiliation: College of Pharmaceutical Science, Southwest University, Chongqing, 400715, China; Chongqing Prevention and Control Center of Animal Desease, Chongqing, 400120, China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Chongqing Prevention and Control Center of Animal Desease, Chongqing, 400120, China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Fan
authors.affiliation: Thermo Fisher Scientific, Shanghai, 201206, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Liao
authors.affiliation: College of Pharmaceutical Science, Southwest University, Chongqing, 400715, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Chongqing Prevention and Control Center of Animal Desease, Chongqing, 400120, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Su
authors.affiliation: College of Pharmaceutical Science, Southwest University, Chongqing, 400715, China. Electronic address: xuegangli@swu.edu.cn.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001599:Berberine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D001682:Biological Availability; D001826:Body Fluids; D002851:Chromatography, High Pressure Liquid; D039323:Coptis / Q000737:chemistry; D005243:Feces; D016014:Linear Models; D008297:Male; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: C000604411:8-cetylberberine; D010936:Plant Extracts; D001599:Berberine
keywords: 8-cetylberberine; LC/MS/MS; excretion; metabolite; pharmacokinetics