title: Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method.
abstract: A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid-liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two-compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetamino-isocorydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In vivo, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetamino-isocorydine could not easily pass through the blood brain barrier. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful information for the in vivo pharmacology of 8-acetamino-isocorydine, and can be applied to new drug research.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmacy, Lanzhou University, Lanzhou 730000, China ; Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Junxi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Duolong
authors.initials: D
authors.lastname: Di
authors.affiliation: Institute of Biology, Gansu Academy of Sciences, Lanzhou 730000, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Liu
keywords: 8-Acetamino-isocorydine; AICD, 8-acetamino-isocorydine; AUC, area under concentration-time curve; Alkaloids; F, absolute bioavailability; HPLC-DAD, high-performance liquid chromatography with diode-array detection; HPLC-UV, high-performance liquid chromatography coupled with ultraviolet detection; High-performance liquid chromatography with diode-array detection; ICD, isocorydine; IS, internal standard; LC-ESI-MS/MS, high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry; LLE, liquid-liquid extraction; LLOQ, lower limit of quantification; LOD, limit of detection; Pharmacokinetics; QC, quality control; RE, relative error; RP, reverse phase; RSD, relative standard deviation; SD, standard deviation.; Tissue distribution