丹参二萜醌组分及其固体分散体微丸中主要成分在大鼠体内的药动学研究  

Pharmacokinetics of main components in Salvia Miltiorrhizae Radix et Rhizoma diterpene quinones composition and its solid dispersion micro-pellets in rats in vivo

作　　者：郁丹红[1,2] 贾晓斌[1,2] 施亚琴[2] 萧伟[3] 

机构地区：[1]南京中医药大学,江苏南京210046 [2]江苏省中医药研究院国家中医药管理局中药释药系统重点研究室,江苏南京210028 [3]江苏康缘药业股份有限公司中药制药过程新技术国家重点实验室,江苏连云港222001

出　　处：《中草药》2013年第7期851-857,共7页Chinese Traditional and Herbal Drugs

基　　金：江苏省中医药领军人才项目(2006);中药制药过程新技术国家重点实验室开放基金(SKL2010Z0303)

摘　　要：目的建立大鼠血浆中丹参二萜醌组分中4个主要成分二氢丹参酮I、丹参酮I、隐丹参酮及丹参酮IIA的UPLC-MS／MS测定方法，用于丹参二萜醌组分及其固体分散体微丸的药动学研究。方法SD大鼠分别ig给予丹参二萜醌组分固体分散体微丸及其原料药后，于不同时问点采集血浆样本，UPLC—MS／MS（以多反应离子监测方式）进行正离子检测，测定二氢丹参酮I、丹参酮I、隐丹参酮及丹参酮IIA血药浓度，DAS2．1．1软件计算丹参二萜醌组分固体分散体微丸及其原料药在大鼠体内的主要药动学参数。结果血浆中丹参二萜醌组分中4个主要成分目内、日间精密度（RSD）均小于14．6％，提取回收率均大于74．49％。药动学研究结果表明，与ig丹参二萜醌组分原料药相比，ig给予其固体分散体微丸后，丹参二萜醌组分中4个主要成分的Cmax和AUC0-∞均不同程度地提高（尸〈0．05）。结论本方法专属性强、灵敏度高，适用于丹参二萜醌组分及其固体分散体微丸中多成分的药动学研究；固体分散体微丸技术通过增加丹参二萜醌组分的溶解性，促进其在体内的吸收，各主要成分的相对生物利用度为原料药的138％-204％。Objective To establish a UPLC-MS/MS method for determining the plasma concentration of dihydrotanshinone I, tansbinone I, cryptotanshinone, and tanshinone IIA in rats, and to study the pharmacokinetics of Salvia miltiorrhiza diterpene quinones composition （SMDQC） and its solid dispersion micro-pellets （SDMP）. Methods Sprague-Dawley rats were ig administered with SMDQC and its SDMP, respectively. Then the blood samples were obtained at different time points. Electrospray ionization （ESI） source was applied and operated in the positive ion mode. The plasma concentration of dihydrotanshinone I, tanshinone I, cryptotanshinone, and tanshinone IIA was then detected by UPLC-MS/MS, and the pharmcoknetic parameters were calculated by DAS 2.1.1 program. Results The RSDs of intra- and inter-day precisions of all analytes were less than 14.6%, and the average recoveries of the four active constituents were more than 74.49%. The pharmacokinetic results showed that after ig administration of SDMP, Cmax and AUC0-∞ of the four active constituents increased significantly compared with those of SMDQC. Conclusion The method has the high sensitivity and selectivity, and proves to be suitable for the pharmacokinetic study of SMDQC and its SDMP. The results show that the SDMP could enhance the solubility of SMDQC to improve its absorption. The relative bioavailability of the four representative constituents is 138%--204% of the crude drug.

关 键 词：丹参二萜醌组分 固体分散体微丸 二氢丹参酮I 丹参酮I 隐丹参酮 丹参酮IIA 药动学 UPLC-MS MS 

分 类 号：R969.1[医药卫生—药理学]