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建立一种用于测定大鼠血浆和组织中钩吻素子的液相色谱-质谱联用方法:应用于药代动力学和组织分布研究。

Development of a liquid chromatography with mass spectrometry method for the determination of gelsemine in rat plasma and tissue: Application to a pharmacokinetic and tissue distribution study.

作者信息

Zhang Shuangshuang, Hu Shuping, Yang Xiangxiang, Shen Jiaqi, Zheng Xiaoyong, Huang Kexin, Xiang Zheng

机构信息

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

出版信息

J Sep Sci. 2015 Mar;38(6):936-42. doi: 10.1002/jssc.201401168. Epub 2015 Feb 10.

Abstract

Gelsemine from Gelsemium elegans Benth is a potential anesthetic and analgesic agent with no physical dependence and opiate addiction. This study was aimed at developing an ultrafast liquid chromatography coupled to tandem mass spectrometry method to quantify gelsemine in rat plasma and tissues. Plasma and tissues were processed with acetonitrile precipitation, and dendrobine was chosen as the internal standard. Sample separation was performed on an ACQUITY HSS T3 column. The mobile phase consisted of acetonitrile and 0.1% formic acid aqueous solution. Multiple reactions monitoring mode was utilized to detect the compounds of interest. The mass spectrometer was operated in the positive ion mode for detection. The MS/MS ion transitions monitored were m/z 323.2→70.5 for gelsemine and 264.2→108.05 for dendrobine, respectively. The calibration curves were linear over the range of 1-500 ng/mL in all biological matrices. The lower limit of quantification for rats plasma and tissues was 1.0 ng/mL. The values for inter- and intraday precision and accuracy were well within the ranges acceptable (< 15%). It was successfully applied to the pharmacokinetic and tissue distribution studies of gelsemine after intravenous doses of 5, 2, and 0.5 mg/kg in rats. These data of gelsemine would be useful for clinical application and further development.

摘要

来自断肠草的钩吻素是一种潜在的麻醉和镇痛剂,无身体依赖性和阿片类成瘾性。本研究旨在建立一种超快速液相色谱-串联质谱法来定量大鼠血浆和组织中的钩吻素。血浆和组织采用乙腈沉淀法处理,选择石斛碱作为内标。样品在ACQUITY HSS T3柱上进行分离。流动相由乙腈和0.1%甲酸水溶液组成。采用多反应监测模式检测目标化合物。质谱仪在正离子模式下运行进行检测。监测的MS/MS离子跃迁分别为钩吻素的m/z 323.2→70.5和石斛碱的m/z 264.2→108.05。在所有生物基质中,校准曲线在1-500 ng/mL范围内呈线性。大鼠血浆和组织的定量下限为1.0 ng/mL。日内和日间精密度和准确度的值均在可接受范围内(<15%)。该方法成功应用于大鼠静脉注射5、2和0.5 mg/kg剂量钩吻素后的药代动力学和组织分布研究。这些钩吻素的数据将有助于临床应用和进一步开发。

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