HPLC - 荧光检测法研究半乳糖化阿霉素白蛋白纳米粒在小鼠体内的药动学分布

 目的 建立反相高效液相色谱 - 荧光检测法研究 半乳糖化阿霉素白蛋白纳米粒在小鼠体内的药动学 。 方法 α - 萘酚为内标，采用 C₁₈ 色谱柱，流动相为甲醇 - 乙腈 -0.02 mol·L^-1 磷酸二氢铵 - 冰醋酸（ 52 ∶ 5 ∶ 43 ∶ 0.6 ），流速： 0.9 mL · min^-1 ；荧光检测器 <> λ (Ex)=246 nm ； <> λ (Em)=555 nm 。 结果 小鼠尾静脉给药后，在规定时间取样，测定阿霉素在小鼠血浆、心、肝、脾、肺、肾中的浓度。与普通阿霉素注射剂相比， 半乳糖化 阿霉素白蛋白纳米粒对肝的靶向性明显提高。 结论 所建 HPLC 用于阿霉素体内分布研究结果良好， 阿霉素白蛋白纳米粒 和 半乳糖化阿霉素白蛋白纳米粒 具有良好的肝脏靶向性；与白蛋白纳米粒相比，半乳糖化白蛋白纳米粒的肝脏靶向性进一步提高，具有自身被动靶向和受体介导的主动靶向的“双靶向”特征。

Pharmacokinetics of Galactosyl Adriamycin BSA Nanoparticles in Mice by RP-HPLC with Fluorescence Detection

OBJECTIVE To study the pharmacokinetic parameters of glactosyl adriamycin bovine serum albumin nanoparticles (ADM-GBN) in mice. METHODS The sample was separated on a C18 column with α-naphthol as the internal standard. The mobile phase consisted of methanol-acetonitrile -0.02 mol·L-1 NH4H2PO4-acetic acid（52∶5∶43∶0.6） at the flow rate of 0.9 mL·min-1. The detection was completed at 246 nm as Ex wavelength and 555 nm as Em wavelength by a fluorescent detector. RESULTS After intravenous injection in mice, the concentrations of adriamycin in mice plasma, heart, liver, lung, kidney and spleen were determined respectively by HPLC. The drug concentration of ADM-GBN showed more remarkable hepatic accumulation than free adriamycin. CONCLUSION The established HPLC method is easy to be applied to study the pharmacokinetics and distribution of adriamycin. Both ADM-BN and ADM-GBN can change the body distribution of ADM and liver targeting. After coupling BN with IME-thioglactose, GBN showed even more remarkable hepatic accumulation, which may mainly result from passive and active liver targeting.