title: Pharmacokinetics, tissue distribution, and excretion studies of l-isocorypalmine using ultra high performance liquid chromatography with tandem mass spectrometry.
abstract: l-Isocorypalmine is a newly identified metabolite of l-tetrahydropalmatine with a unique dual pharmacological profile as a partial dopamine receptor 1 agonist and dopamine receptor 2 antagonist properties for treating cocaine use disorder. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, and excretion of l-isocorypalmine in Sprague-Dawley rats. A sensitive and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for determination of l-isocorypalmine in biological samples. The biological samples were extracted by liquid-liquid extraction and separated on a Bonshell ASB C18column (2.1 × 100 mm, 2.7 μm, Agela) with gradient mobile phase at the flow rate of 0.2 mL/min. The detection was performed by positive electrospray ionization with multiple reaction monitoring mode. Satisfactory linearity, precision, accuracy, extraction recovery, and acceptable matrix effect were achieved. The quantitative method was successfully applied to the pharmacokinetics, tissue distribution, and excretion study of l-isocorypalmine. The results showed that l-isocorypalmine was rapidly distributed, and eliminated from rat plasma and manifested linear dynamics in a dose range of 7.5-15 mg/kg. In addition, the results would be helpful for further clinical reference of l-isocorypalmine as a potential candidate drug for the treatment of cocaine addiction.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Wang
authors.affiliation: McLean Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Wang
authors.affiliation: McLean Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: David Y W
authors.initials: DY
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Dai
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D001600:Berberine Alkaloids; C000589018:isocorypalmine
keywords: 
  l-isocorypalmine; excretion; pharmacokinetics; tissue distribution; ultra performance liquid chromatography