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采用液相色谱-串联质谱法同时测定大鼠血浆中催吐萝芙木中的五种生物碱:在正常和2型糖尿病大鼠中的比较药代动力学研究应用

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC-MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats.

作者信息

Wang Ning, Xie Yue-Wu, Li Meng-Yu, Li Fei-Fei, Zhang Li-Yuan, You Yu-Lin, Wang Shu-Qi

机构信息

School of Pharmaceutical Sciences, Shandong University, Jinan, P. R. China.

Department of general surgery, People's Hospital Binzhou, Binzhou, P. R. China.

出版信息

J Sep Sci. 2021 Apr;44(7):1391-1403. doi: 10.1002/jssc.202000914. Epub 2021 Feb 10.

Abstract

Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple-reaction-monitoring mode with an electrospray positive-ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single-dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.

摘要

催吐萝芙木广泛分布于非洲和亚洲的热带地区,在中国已被用于传统民间医学。吲哚生物碱被发现是主要的生物活性成分,而糖尿病对这些成分药代动力学参数的影响在体内尚未得到体现。在本研究中,开发并验证了一种高效灵敏的液相色谱 - 串联质谱法,用于同时测定大鼠体内催吐萝芙木的五种成分。采用电喷雾正离子源在多反应监测模式下进行检测。验证参数均符合现行标准。所建立的方法有效地用于比较正常大鼠和2型糖尿病大鼠体内五种生物碱(利血平、育亨宾、阿马林、阿马里新和蛇根碱)的药代动力学行为。在正常大鼠和糖尿病大鼠口服100和200 mg/kg体重后,测定了这五种生物碱的单剂量药代动力学参数。结果表明,糖尿病显著改变了大鼠口服给药后育亨宾、阿马林和阿马里新的药代动力学特征。这是一次尝试,为临床医生提供一些证据,可能作为临床实践中使用抗糖尿病药物的指导。

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