title: Pharmacokinetic studies of phellodendrine in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry.
abstract: Phellodendrine, a quaternary ammonium alkaloid extracted from the dried bark of Phellodendrom chinensis Schneid and Phellodendrom amurense Rupr, has the effect of suppressing cellular immune response, reducing blood pressure and antinephritis. However, few investigations have been conducted for the pharmacokinetic study of phellodendrine. Thus, a rapid, simple and reliable ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ MS/MS) method has been established for quantification of phellodendrine in rat plasma and tissues by using magnoflorine as internal standard. The chromatographic separation was achieved on an Agilent ZORBAX SB-C18 column (4.6mm×50mm, 1.8μm) by gradient elution using 0.1% aqueous formic acid (A) and methanol (B). Triple quadrupole mass detection with multiple reaction monitoring mode was used to monitor the ion transitions, at m/z 342.20→192.20 for phellodendrine and m/z 342.20→58.20 for internal standard, respectively. The developed method was fully validated and successfully applied to the pharmacokinetics and tissue distribution study of phellodendrine after intravenous administration. The lower limits of quantification were 0.5ng/mL for plasma samples, 2.5ng/g for brain and 1ng/g for other tested tissues. Precisions and accuracy values were within the Food and Drug Administration acceptance criteria, the recovery and matrix effects were between 87.8-113.5%. The area under the curve (AUC0-t) ranged from 15.58 to 57.41mg/L min and Cmax were between 1.63-4.93mg/L. The results showed that phellodendrine was eliminated in 120min in plasma and most of tissues and the highest concentrations of phellodendrine were found in the kidney. This study may provide a basis for the further study of phellodendrine.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xin-Guang
authors.initials: XG
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 104yang104@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D057230:Limit of Detection; D008099:Liver / Q000378:metabolism; D008297:Male; D011807:Quinolizines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D004365:Drugs, Chinese Herbal; D011807:Quinolizines; C079418:phellodendrine
keywords: Cortex phellodendri; Pharmacokinetic; Phellodendrine; Tissue distribution; UHPLC–MS/MS