中国药理学通报Issue(1)：108-112,5.DOI:10.3969/j.issn.1001-1978.2014.01.023
酶解法与LC-MS-MS相结合研究灯盏乙素在健康人体内的药代动力学
Pharmacokinetic study of scutellarin in healthy volunteers by enzymatic hydrolysis and LC-MS-MS analysis
摘要
Abstract
Aim To establish a combined method ofβ-glucuronidase hydrolysis and LC-MS-MS analysis for the determination of scutellarein in human plasma, and investigate the pharmacokinetics of scutellarin prepara-tion in healthy male volunteers. Methods Plasma samples were prepared by enzymolysis with β-glucu-ronidase and protein precipitation with methanol. The analytes scutellarein and quercetin ( IS ) were separa-ted on an Agilent ZORBAX SB C18 column ( 2. 1 mm × 150 mm, 5 μm) with the mobile phases consisting of acetonitrile, methanol and water. Multiple reaction monitoring ( MRM) on MS was used to monitor precur-sor to produce ion transitions of m/z 285. 0→136. 8 for scutellarein and m/z 301. 1→120. 8 for IS. After method validation, this method was applied to deter-mine the plasma concentration of scutellarein in 12 male volunteers following single oral administration of 120 mg scutellarin preparation. Drug And Statistic soft-ware (1. 0) was used to process data and the pharma-cokinetic parameters were calculated. Results The assay was validated with linear range of 4 . 01-513. 38μg · L-1 for scutellarein. The intra- and inter-batch precisions ( RSD%) were within 7. 22%. The absolute recoveries were more than 84. 23%. The pharmacoki-netic parameters after a single dose were as follows:Cmax (μg · L-1 ): 159. 97 ± 58. 14; AUC(0-19) (μg · L-1·h):1151. 37 ±279. 80; AUC(0-∞)(μg·L-1· h):1194. 13 ± 264. 51; Tmax ( h):6. 33 ± 1. 67; T1/2 (h):2. 83 ± 0. 60. Conclusion The assay method is proved to be sensitive, accurate and convenient. It can be successfully applied to a pharmacokinetic study of scutellarin in healthy male volunteers.关键词
灯盏乙素/灯盏乙素苷元/β-葡萄糖醛酸苷酶/酶解/LC-MS-MS/药代动力学Key words
scutellarin/scutellarein/β-glucuroni-dase/enzymatic hydrolysis/LC-MS-MS/pharmacoki-netics分类
医药卫生引用本文复制引用
储继红,张军,李长印,邹冲,刘芳,居文政..酶解法与LC-MS-MS相结合研究灯盏乙素在健康人体内的药代动力学[J].中国药理学通报,2015,(1):108-112,5.基金项目
国家科技部“重大新药创制”科技重大专项( No 2012ZX09303009-002) （ No 2012ZX09303009-002）
江苏省中医药领军人才( No LJ200906) （ No LJ200906）
