title: Determination of protein-unbound rhynchiphylline brain distribution by microdialysis and ultra-performance liquid chromatography with tandem mass spectrometry.
abstract: The stem with hook of Uncaria rhynchophylla (Chinese herbal name Gou-Teng) is a traditional Chinese medicine that has been ethnopharmacologically used to extinguish wind and clean interior heat. Rhynchophylline (RHY), a tetracyclic oxindole alkaloid isolated from U. rhynchophylla, displays significant antineuroinflammatory effects. However, there is no evidence to indicate that rhynchophylline can cross the blood-brain barrier and be detected in the brain. In this study, an in vivo microdialysis sampling method coupled with UPLC/MS/MS was employed for the continuous simultaneous monitoring of unbound RHY in rat blood and brain. The precursor ion → product ion transition at m/z 385.2 → 160.0 for rhynchophylline was monitored. A calibration curve gave good linearity (r>0.996) over the concentration range from 0.5 to 1000 ng/mL. The results demonstrated that rhynchophylline could be detected in the brain and plasma from 15 min to 6 h after its administration (1 or 10 mg/kg, i.v.). All the pharmacokinetic parameters of rhynchophylline in the brain and plasma were obtained. These results show that rhynchophylline can cross the blood-brain barrier and they provide useful clinical information.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Lee
authors.forename: Thomas Y
authors.initials: TY
authors.lastname: Hsueh
authors.forename: Lie-Chwen
authors.initials: LC
authors.lastname: Lin
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D026121:Indole Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D000078183:Oxindoles; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D032070:Uncaria / Q000737:chemistry
chemical_list: D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D000078183:Oxindoles; D011506:Proteins; C052714:rhyncophylline
keywords: UPLC/MS/MS; blood-brain barrier; microdialysis; pharmacokinetic parameters; rhynchiphylline