Acta Pharmaceutica Sinica B 2015;5(3):238-245

doi:10.1016/j.apsb.2015.03.012

Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method.

Yali CHEN 1 ; Qian YAN 2 ; Mei ZHONG 2 ; Quanyi ZHAO 3 ; Junxi LIU 2 ; Duolong DI 2 ; Jinxia LIU 4

Affiliations

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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

Country

China

Language

English

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.