负载肿节风活性组分的聚多巴胺滴丸在大鼠体内的药代动力学研究

Pharmacokinetic study of Polydopamine Guttate Pills loaded with active components of Sarcandrae Herba in rats

建立用于血浆中肿节风活性成分含量测定的超高效液相色谱-串联质谱(UHPLC-MS/MS),并应用于多剂型的药物动力学研究。SD大鼠灌胃肿节风提取液、市售肿节风滴丸和负载肿节风活性组分的聚多巴胺(PDA-Sg)滴丸3种不同制剂后,于不同时间点经眼眶静脉丛取血,血浆样品经蛋白沉淀,采用Acquity UPLC C色谱柱(2.1 mm×100 mm, 1.7μm)分离,流动相为0.2%甲酸水-乙腈,梯度洗脱;在多反应监测(MRM)模式下负离子测定;采用DAS 2.0软件拟合计算药动学参数。结果显示,除肿节风提取液组无法直接检测到新绿原酸和隐绿原酸外,各组大鼠血浆的各时间点均可检测到4种成分(新绿原酸、隐绿原酸、异嗪皮啶和迷迭香酸)。滴丸制剂组在各时间点均表现出显著的药物含量增加;通过PDA对肿节风主要成分的负载,能够有效提高药物在血液中的暴露量(新绿原酸、隐绿原酸、异嗪皮啶和迷迭香酸的AUC分别达到了市售滴丸的2.45、32.90、1.54、4.81倍)。该研究证明了上述多成分体外-体内传递过程的可测性,表明PDA-Sg滴丸能够有效延缓药物在血液中的消除时间,提高生物利用度,为该剂型的生产提供相应的理论数据。

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC Ccolumn(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUCof neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.