隐丹参酮及丹参酮提取物在大鼠体内药动学比较研究

 目的建立LC-MS-MS测定大鼠血浆隐丹参酮的浓度,比较隐丹参酮单体及丹参酮提取物在大鼠体内的药动学特点,评价丹参酮提取物中其他成分对隐丹参酮药动学的影响。方法大鼠分别ig给予隐丹参酮5.7 mg·kg^-1或丹参酮提取物(相当于隐丹参酮5.7 mg·kg^-1)后,眼底静脉丛取血,分离血浆,经甲基叔丁基醚液-液萃取后进行LC-MS-MS分析,测定血浆隐丹参酮浓度,经3P97程序处理数据。结果隐丹参酮在0.1～50μg·L^-1内线性良好,最低检测限为0.1μg·L^-1,方法回收率为94.0%～103.8%。大鼠灌胃隐丹参酮和丹参酮提取物后的药-时曲线分别符合一房室和二房室模型。灌胃丹参酮提取物后,与灌胃隐丹参酮相比,前者测得的隐丹参酮ρ_max和AUC_0-t分别比后者增大3.4和3.5倍。结论本实验建立的LC-MS-MS测定法,专属、准确、灵敏,适用于隐丹参酮单体和丹参酮提取物中隐丹参酮的药动学研究。研究结果表明,脂溶性丹参酮成分可促进隐丹参酮的吸收和/或转化,提高隐丹参酮的生物利用度,对认识丹参酮成分的协同作用和临床药效提供了依据。

Comparative Study on Pharmacokinetics of Cryptotanshinone and Tanshinones Extract of Salvia miltiorrhiza Bge. in Rats

OBJECTIVE To develop a LC-MS-MS method for determination of the concentration of cryptotanshinone in rat plasma and comparative study of the pharmacokinetics of cryptotanshinone and tanshinones extract of Salvia miltiorrhiza Bge.in rat,and to assess the effect of other tanshinone components on the pharmacokinetics of cryptotanshinone.METHODS Rats received 5.7 mg·kg^-1 cryptotanshinone or extract from Salvia miltiorrhiza Bge.(equal to cryptotanshinone 5.7 mg·kg^-1) by oral gavarge.Blood samples were collected from the eye ophthalmic vein jungle venous plexus.After liquid liquid extraction with methyl t-butyl ether,plasma concentrations of cryptotanshinone was measured.The pharmacokinetic parameters were calculated with 3P97 program.RESULTS A good linear relationship of cryptotanshinone was obtained from 0.1 to 50 μg·L^-1,the lowest limits of determination were 0.1 μg·L^-1.The method recoveries were all from 94.0%～103.8%.The plasma concentration-time curves of cryptotanshinone were best fitted with one-compartment and two-compartment models for cryptotanshinone and tanshinones extract of Salvia miltiorrhiza Bge.,respectively.The AUC_0-t and ρ_max of cryptotanshinone were much greater when the extract was administrated.CONCLUSION The LC-MS-MS method was selective,accurate and sensitive.The results indicated that the tanshinones extract of Salvia miltiorrhiza Bge.had significant effect on the absorption and/or transformation of cryptotanshinone therefore affecting the bioavailability of cryptotanshinone significantly.These results are important for the clinical indication and understanding of the pharmacokinetics and synergism of cryptotanshinone and tanshinones extract of _{Salvia miltiorrhiza} Bge.