A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite madecassic acid in rat plasma: comparison pharmacokinetics in normal and collagen-induced arthritic rats  

作　　者：WANG Ting LENG Dan-Dan GAO Fei-Fei JIANG Chun-Jie XIA Yu-Feng DAI Yue 

机构地区：[1]Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University [2]Department of Chinese Materia Medica Analysis, China Pharmaceutical University

出　　处：《Chinese Journal of Natural Medicines》2014年第12期943-951,共9页中国天然药物（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(No.81374038,81173631);the Jiangsu Overseas Research&Training Program for University Prominent Young&Middle-aged Teachers and Presidents;sponsored by Qing Lan Project,College Students Innovation Project for the R&D of Novel Drugs(No.J1030830);partially funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions

摘　　要：To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric(LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis(CIA) rats. Glycyrrhetinic acid was used as the internal standard(IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1%(V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring(SIM) mode. In normal and CIA rats, madecassoside(30 mg·kg-1) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10–1 000 ng·mL-1 with the square regression coefficient(r) of 0.998 9, while for madecassic acid, the linear range was 10–500 ng·mL-1 with the square regression coefficient(r) of 0.996 1. The lower limit of quantification was 10 ng·mL-1 for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between –0.95% and 6.30% for madecassoside and between –1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA rats compared with normal rats. Along with repeated adminiTo develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric （LC-ESI-MS） method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis （CIA） rats. Glycyrrhetinic acid was used as the internal standard （IS）. Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% （V/V） formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring （SIM） mode. In normal and CIA rats, madecassoside （30 mg·kg^-1） was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10-1 000 mg·kg^-1 with the square regression coefficient （r） of 0.998 9, while for madecassic acid, the linear range was 10-500 mg·kg^-1 with the square regression coefficient （r） of 0.996 1. The lower limit of quantification was 10 mg·kg^-1 for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between -0.95% and 6.30% for madecassoside and between -1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were 〉 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the Cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, Cmax and A UC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA rats compared wit

关 键 词：MADECASSOSIDE Madecassic acid LC-ESI-MS PHARMACOKINETICS Collagen-induced arthritis 

分 类 号：R965[医药卫生—药理学]