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液相色谱-质谱联用法同时测定大鼠血浆中5种三萜酸及其在枇杷叶有效部位口服给药后药代动力学研究中的应用

Simultaneous determination of five triterpene acids in rat plasma by liquid chromatography-mass spectrometry and its application in pharmacokinetic study after oral administration of Folium Eriobotryae effective fraction.

作者信息

Li Zhen-Hua, Zhu He, Cai Xue-Ping, He Dan-Dan, Hua Jun-Lei, Ju Jian-Ming, Lv Han, Ma Li, Li Wei-Lin

机构信息

Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210046, People's Republic of China.

Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, 210028, People's Republic of China.

出版信息

Biomed Chromatogr. 2015 Dec;29(12):1791-7. doi: 10.1002/bmc.3497. Epub 2015 Jun 1.

DOI:10.1002/bmc.3497
PMID:26033261
Abstract

Folium Eriobotryae effective fraction (FEA), the extract of Folium Eriobotryae, had been used as anti-hyperglycemia and anti-hyperlipemia medicine in China. A previous study indicated that euscaphic acid, maslinic acid, corosolic acid, oleanolic acid and ursolic acid, the five structurally similar triterpene acids (containing two groups of structural isomers), are the major components of FEA. In the present study, we developed a specific and reliable LC-MS method for simultaneous determination of the five triterpene acids in rat plasma, and further investigated their pharmacokinetic properties after oral administration of FEA. Following a simple sample preparation, chromatographic separation was achieved on a C18 column with a mobile phase composed of methanol-0.1% ammonium acetate (80:20, v/v). Quantification was achieved by monitoring the selected ions at m/z 487.6 for euscaphic acid, m/z 471.5 for maslinic acid and corosolic acid, m/z 455.5 for oleanolic acid and ursolic acid and m/z 469.5 for internal standard. The method was validated to be specific, accurate and precise over the concentration ranges of 10-3000 ng/mL with limits of detections of 5 ng/mL for the five triterpene acids. Finally, the method was successfully applied to the pharmacokinetic study of the five structurally similar triterpene acids in rats after oral administration of FEA.

摘要

枇杷叶有效部位(FEA),即枇杷叶提取物,在中国已被用作抗高血糖和抗高血脂药物。先前的一项研究表明,委陵菜酸、山楂酸、科罗索酸、齐墩果酸和熊果酸这五种结构相似的三萜酸(包含两组结构异构体)是FEA的主要成分。在本研究中,我们开发了一种特异性强且可靠的LC-MS方法,用于同时测定大鼠血浆中的这五种三萜酸,并进一步研究了口服FEA后它们的药代动力学性质。经过简单的样品制备后,在C18柱上进行色谱分离,流动相为甲醇-0.1%醋酸铵(80:20,v/v)。通过监测委陵菜酸的m/z 487.6、山楂酸和科罗索酸的m/z 471.5、齐墩果酸和熊果酸的m/z 455.5以及内标的m/z 469.5处的选定离子来进行定量。该方法在10 - 3000 ng/mL的浓度范围内被验证具有特异性、准确性和精密度,这五种三萜酸的检测限均为5 ng/mL。最后,该方法成功应用于大鼠口服FEA后这五种结构相似的三萜酸的药代动力学研究。

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