中国药理学通报2011，Vol.27Issue(9)：1313-1316,4.DOI:10.3969/j.issn.1001-1978.2011.09.031
LC-MS/MS法测定人血浆中甘草次酸及其临床药代动力学研究
A sensitive LC/MS/MS method for the determination of glycyrrhetic acid in human plasma and application to pharmacokinetic study
摘要
Abstract
Aim To establish a LC-MS-MS method for the determination of glycyrrhetic acid( CA ), a major metabolite of glycyrrhizin( CLY ) in human plasma,and to investigate the pharmacokinetics of GA in Glycyrrhizinate Capsules in Chinese healthy volunteers.Methods Glycyrrhizinate Capsules were orally administrated to healthy volunteers at a single dose of 150 mg. Blood samples were then collected and extracted by ethyl acetate. GA and internal standard ( IS ),prednisolone. were subjected to LC-MS/MS analysis with electro-spray ionization ( ESI ) in the multiple reaction monitoring ( MRM ) mode. Chromatographic separation was performed on an Agilent ZORBAX SB Cl8( 3.0 mm × 100 mm id,5 μm ) within 5 min, with the mobile phase of methanol : acetonitrile : water( 15 : 60 : 25 .Ⅴ : Ⅴ : Ⅴ) containing 0. 2％ acetic acid and 5 mmol · L-1ammonium acetate. The precursor to produce transitions monitored for GA and IS were m/z 469. 4→355. 2 and 358. 9→279. 9 respectively. Results Calibration curves were linear ( r2 ＞ 0. 995 ) over the concentration range from 1. 5 to 192 μg · L-1 for GA with the absolution recovery greater than 78. 0％ . The pharruacokinetic parameters after a single dose were as follows: ( 73. 85 ± 25. 25 ) μg · L-1 ( Cmax ), 11. 50 ±3. 07 h( Tmax ), ( 11. 82 ±3. 56 ) h ( T1/2β ), ( 1252. 49 ±489. 06 )μg · h · L-1( AUC060 ).Conclusion The assay method is proved to be sensitive. accurate and convenient. It can be applied to the pharmacokinetic study of glycyrrhetic acid. The peak time of GLY in human is long after taking Glycyrrhizinate Capsule orally. The drug-time curve appears double peak in about 50% of healthy volunteers.关键词
甘草酸二铵胶囊/甘草次酸/代谢产物/LC-MS/MS/血药浓度/药代动力学Key words
glycyrrhizinate capsule / glycyrrhetic acid /metabolite/ LC/MS/MS/ drug plasma concentration/pharmacokinetic study分类
医药卫生引用本文复制引用
张军,陈玟,居文政,刘芳,邹冲..LC-MS/MS法测定人血浆中甘草次酸及其临床药代动力学研究[J].中国药理学通报,2011,27(9):1313-1316,4.基金项目
国家重大新药创制课题:中药新药临床评价研究技术平台(南京)建设资助项目(No 2008ZX09312-004) （南京）
江苏省中医药领军人才资助项目(No LJ200906) （No LJ200906）
