目的 建立大鼠血漿中丹參二萜醌組分中4個主要成分二氫丹參酮I、丹參酮I、隱丹參酮及丹參酮II_A的UPLC- MS/MS測定方法，用于丹參二萜醌組分及其固體分散體微丸的藥動學(xué)研究。方法 SD大鼠分別ig給予丹參二萜醌組分固體分散體微丸及其原料藥后，于不同時間點采集血漿樣本，UPLC-MS/MS（以多反應(yīng)離子監(jiān)測方式）進行正離子檢測，測定二氫丹參酮I、丹參酮I、隱丹參酮及丹參酮II_A血藥濃度，DAS 2.1.1軟件計算丹參二萜醌組分固體分散體微丸及其原料藥在大鼠體內(nèi)的主要藥動學(xué)參數(shù)。結(jié)果 血漿中丹參二萜醌組分中4個主要成分日內(nèi)、日間精密度（RSD）均小于14.6%，提取回收率均大于74.49%。藥動學(xué)研究結(jié)果表明，與ig丹參二萜醌組分原料藥相比，ig給予其固體分散體微丸后，丹參二萜醌組分中4個主要成分的C_max和AUC_0~∞均不同程度地提高（P＜0.05）。結(jié)論 本方法專屬性強、靈敏度高，適用于丹參二萜醌組分及其固體分散體微丸中多成分的藥動學(xué)研究；固體分散體微丸技術(shù)通過增加丹參二萜醌組分的溶解性，促進其在體內(nèi)的吸收，各主要成分的相對生物利用度為原料藥的138%～204%。

Objective To establish a UPLC-MS/MS method for determining the plasma concentration of dihydrotanshinone I, tanshinone I, cryptotanshinone, and tanshinone II_A 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 II_A 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, C_max and AUC_0-∞ 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.

江蘇省中醫(yī)藥領(lǐng)軍人才項目（2006）；中藥制藥過程新技術(shù)國家重點實驗室開放基金（SKL2010Z0303）