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LC-MS/MS法测定大鼠血浆和组织中朝藿定B:在药代动力学和组织分布研究中的应用

Determination of Epimedin B in Rat Plasma and Tissue by LC-MS/MS: Application in Pharmacokinetic and Tissue Distribution Studies.

作者信息

Feng Qianru, Xu Shunjun, Yu Jiejing, Sun Shuai, Yang Liu

机构信息

Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.

Guangzhou ImVin Pharmaceutical Co., Ltd., Guangzhou 510663, China.

出版信息

J Anal Methods Chem. 2017;2017:7194075. doi: 10.1155/2017/7194075. Epub 2017 Jun 1.

Abstract

A simple, sensitive, and specific liquid chromatography tandem mass-spectrometric method was developed and validated for the determination of epimedin B in rat plasma and tissue samples. After being processed with a protein precipitation method, these samples were separated on an Agilent Eclipse XDB-C column with an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution (32 : 68, v/v). The calibration curve of epimedin B was linear over the concentration range from 1 to 500 ng/mL in plasma and tissue homogenate. The method was then applied to pharmacokinetic and tissue distribution studies after a single oral administration of Herba Epimedii extract to SD rats. Results showed that epimedin B reached the plasma peak concentration at 0.4 h and the terminal elimination half-life was 1.6 h in rat plasma, and the plasma area under the curve from time zero to infinity (AUC ) was 14.35 g/L·h. The concentration distribution of epimedin B in rat tissue was in the following order: liver > ovary > womb > lung > kidney > spleen > heart > brain, indicating that the compound could be widely distributed in rat, and the reproductive system may be the principal target of epimedin B for female rat.

摘要

建立了一种简单、灵敏、特异的液相色谱串联质谱法,用于测定大鼠血浆和组织样品中的朝藿定B,并进行了方法学验证。采用蛋白沉淀法处理后,样品在Agilent Eclipse XDB-C柱上分离,流动相为乙腈和0.1%甲酸水溶液(32∶68,v/v)的等度洗脱体系。朝藿定B在血浆和组织匀浆中的校准曲线在1~500 ng/mL浓度范围内呈线性。将该方法应用于SD大鼠单次口服淫羊藿提取物后的药代动力学和组织分布研究。结果表明,大鼠血浆中朝藿定B在0.4 h达到血药峰浓度,末端消除半衰期为1.6 h,血浆药时曲线下面积(AUC)为14.35 μg/L·h。朝藿定B在大鼠组织中的浓度分布顺序为:肝脏>卵巢>子宫>肺>肾>脾>心脏>脑,表明该化合物在大鼠体内分布广泛,生殖系统可能是朝藿定B对雌性大鼠的主要作用靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2132/5471579/d30c07b5fb76/JAMC2017-7194075.001.jpg

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