Dataset Information

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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC4629263 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chen Yali Y Yan Qian Q Zhong Mei M Zhao Quanyi Q Liu Junxi J Di Duolong D Liu Jinxia J

Acta pharmaceutica Sinica. B 20150416 3

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 ...[more]

PMID: 26579452

Similar Datasets

Project description:Background:In China, the combination of herb Salvia miltiorrhiza Bge. (Danshen) and Carthamus tinctorius L. (Honghua) is an effective treatment for stroke. A previous study showed that the combination of four herbal components: danshensu (DSS), hydroxysafflor yellow A (HSYA), salvianolic acid A (SAA), and salvianolic acid B (SAB) was effective for treatment of cerebral ischemia-reperfusion (I/R) injury in rats. However, the pharmacokinetic characteristics of this formula require further investigation. The present study investigated the pharmacokinetic differences between each component of in two formulas in cerebral I/R injury rats. The influencing factors may affect the compatibility of components were analyzed. Methods:Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO). Rats that underwent MCAO were randomly divided into two groups and administered treatments through the tail vein. Blood samples were collected at predetermined time points following administration. The concentrations of DSS, HSYA, SAB, and SAA in rat plasma were determined using HPLC-DAD, and the main pharmacokinetic parameters were calculated. Pharmacokinetic parameters were calculated using DAS 3.2.6 software and SPSS 23.0 statistical analysis software. Results:Our results showed that DSS, HSYA, SAB, and SAA in MCAO model rats had statistically significant differences in two formulas. For DSS and SAA, pharmacokinetic parameters with statistically significant differences including AUC(0-t), AUMC(0-t), MRT(0-t), VRT(0-t), t1/2z, Vz, CLz, and Cmax (P < 0.01). For HSYA, significant differences in the parameters including AUC(0-t), AUMC(0-t), MRT(0-t), VRT(0-t) (P < 0.01), CLz and Cmax (P < 0.05). Conclusion:The difference in pharmacokinetic parameters in response to each component may have been due to differences in the dosages of the components (HSYA, SAA, SAB) and the compatibility of components. Meanwhile, there were many influencing factors could affect the compatibility of components, such as the metabolism by CYP450 enzymes, plasma protein binding rates, and effects related to the blood-brain barrier (BBB). Moreover, our study provided new insights, such as choosing appropriate dosages of active components of traditional Chinese medicine (TCM) to aid in prevention and treatment of cerebral ischemic diseases. The method and results in this study could provide a foundation for future pharmacological studies of the active components in Danshen and Honghua.

Project description:Lipid nanoparticles (LNPs) have shown great success as drug delivery systems, especially for mRNA vaccines, as those developed during the Covid-19 pandemics. Lipid analysis is critical to monitor the formulation process and control the quality of LNPs. The present study is focused on the development and validation of a high-performance liquid chromatography - diode array detector -evaporative light scattering detector (HPLC-DAD/ELSD) based method for the simultaneous quantification of 7 lipids, illustrating the main components of LNPs: ionizable lipids, the neutral co-lipid cholesterol, phospholipids, hydrophilic polymer-lipids for colloidal stability (e.g., a PEGylated lipid). In particular, this study focuses on two innovative synthetic lipids: a switchable cationic lipid (CSL3) which has demonstrated in vitro and in vivo siRNA transfection abilities, and the palmitic acid-grafted-poly(ethyloxazoline)5000 (PolyEtOx), used as an alternative polymer to address allergic reactions attributed to PEGylated lipids. The HPLC separation was achieved on a Poroshell C18 column at 50 °C using a step gradient of a mobile phase composed of water/methanol mixtures with 0.1% (v/v) trifluoroacetic acid (TFA). This method was validated following ICH Q2(R1) & (R2) guidelines in terms of linearity (R² ≥ 0.997), precision (relative standard deviation on peak areas < 5% for intermediate repeatability), accuracy (recoveries between 92.9% and 108.5%), and sensitivity. Indeed, low detection and quantitation limits were determined (between 0.02 and 0.04 µg and between 0.04 and 0.10 µg, respectively). Due to its high selectivity, this method allowed the analysis of lipid degradation products produced through degradation studies in basic, acidic, and oxidative conditions. Moreover, the method was successfully applied to the analysis of several liposome formulations at two key steps of the development process. Consequently, the reported HPLC method offers fast, versatile, selective and quantitative analysis of lipids, essential for development optimization, chemical characterization, and stability testing of LNP formulations.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets