乳糖脂修饰氧化苦参碱脂质体在家兔体内的药代动力学研究

目的: 建立高效液相色谱法检测乳糖酰磷脂酰乙醇胺修饰的氧化苦参碱脂质体(glycosylation oxymatrine liposome,LML)和普通氧化苦参碱脂质体(oxymatrine liposome,OM-L)在新西兰家兔体内血药浓度。方法: 分别给新西兰家兔耳缘静脉注射LML和OM-L后,于不同时间点从颈静脉取血。血浆经处理后采用高效液相色谱法检测,以槐定碱为内标,采用Hanbon Hedera ODS-2(4.6 mm×150 mm,5 μm)色谱柱,流动相0.05 mol·L^-1磷酸二氢钾-乙腈(93:7),流速1 mL·min^-1,检测波长215 nm。数据使用3P87药代动力学程序进行计算。结果: LML平均包封率为55.48%,平均粒径为80 nm。OM浓度在1.00~120 μg·mL^-1范围内,线性关系良好。血浆中OM提取回收率(n=5)为80.0%~84.0%,RSD≤0.60%。结论: 本方法符合方法学验证基本要求,适合测定OM在新西兰家兔体内的血药浓度;OM在新西兰家兔体内的消除符合二室消除模型。与OM-L相比,LML在体内的AUC值明显增大,清除率明显降低,提高了OM在体内的驻留时间。

Objective: To establish an HPLC method for measurement of serum concentration of glycosylation oxymatrine liposome (LML)and oxymatrine liposome (OM-L)in New Zealand rabbits and explore their pharmacokinetics. Methods: After the administration of LML and OM-L respectively to the New Zealand rabbit ears by intravenous injection,the plasma concentration-time curves were detected.The plasma after treatment was determined by HPLC,sophoridine was employed as an internal standard.The separation was performed on a Hanbon Hedera ODS-2 (4.6 mm×150 mm,5 μm)column and the mobile phase consisted of 0.05 mol·L^-1 potassium dihydrogen phosphate and acetonitrile (93:7)at a flow rate of 1 mL·min^-1,and the detection wavelength was 215 nm.The pharmacokinetics were explored by 3P87 pharmacokinetic program. Results: The average entrapment efficiency of LML were 55.48% and the average particle size were 80 nm.OM had a good linear relationship in 1.00-120 μg·mL^-1 concentration range.The average extraction recovery (n=5)of OM in plasma was 80.0%-84.0%,RSD≤0.60%. Conclusion: The method is convenient,sensitive,and suitable for the determination of OM concentration in plasma of New Zealand rabbits;the elimination of OM in New Zealand rabbits is conformed to two compartment model elimination.Compared with OM-L,the in vivo AUC values of LML increase and the clearance rates decrease obviously,which increases the in vivo retention time of OM.