Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS.
Berberrubine is an isoquinoline alkaloid isolated from Berberis vulgaris L, and it is readily derived from berberine. In this study, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of berberrubine in rat plasma and mouse tissue has been developed. Magnoflorine was employed as an internal standard (IS), and liquid-liquid extraction by ethyl acetate was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1mm×100mm, 1.7μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 322.0→307.0 for berberrubine and m/z 342.8→298.2 for IS. Calibration plots were linear in the range of 2-2000ng/mL for berberrubine in rat plasma and mouse tissue. Mean recoveries of berberrubine in rat plasma ranged from 79.6% to 84.8%. Intra-day and inter-day precision were less than 11%. The accuracy ranged from 93.6% to 106.8%. The method has also been successfully applied in pharmacokinetics and tissue distribution study of berberrubine. The absolute bioavailability of berberrubine was determined to be 31.6%. The results also show that berberrubine is rapidly absorbed and widely distributed in various tissues. The level of berberrubine in liver is highest, and followed by kidney, spleen and heart. Furthermore, the concentration of berberrubine in various tissues could also be predicted by a BP-ANN model.
College of Plant Protection, Anhui Agricultural University, Hefei 230036, China; Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
Xianqin
X
Wang
Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Lishui 323000, China.
Shuanghu
S
Wang
Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
Jianshe
J
Ma
College of Plant Protection, Anhui Agricultural University, Hefei 230036, China.
Tao
T
Ye
Department of Pharmaceutical Sciences, University of California at Irvine, Irvine, USA.
Mengrou
M
Lu
College of Plant Protection, Anhui Agricultural University, Hefei 230036, China.
Miao
M
Fan
College of Plant Protection, Anhui Agricultural University, Hefei 230036, China; Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
Mingjie
M
Deng
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Lufeng
L
Hu
College of Plant Protection, Anhui Agricultural University, Hefei 230036, China. Electronic address: gaozhimou@126.com.
Zhimou
Z
Gao
D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051379:Mice; D008954:Models, Biological; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards; D014018:Tissue Distribution
D001599:Berberine; C115958:berberrubine
BP-ANN; Berberrubine; Pharmacokinetics; Tissue distribution; UPLC-MS/MS