盐酸表阿霉素-紫杉醇复方脂质体的制备

Preparation of Epirubicin Hydrochloride-Paclitaxel Compound Liposomes

目的进行盐酸表阿霉素-紫杉醇复方脂质体的制备工艺研究并建立同时测定两药含量的高效液相色谱方法。方法采用薄膜分散-pH梯度法制备复方脂质体。Venusil MP C18色谱柱（250cm×4.6mm,5μm）;流动相：乙腈-甲醇-10mmol/L磷酸盐缓冲液（pH2.5）（36∶32∶32）;检测波长：227nm;流速：1.0ml/min。结果盐酸表阿霉素与紫杉醇出峰时间分别为4.2、14.8min;线性方程分别为Y=216300X-34525（r=0.9998,0.1~25μg/ml）,Y=161480X-84107（r=0.9998,0.3~75μg/ml）。盐酸表阿霉素和紫杉醇的回收率均在99%~101%范围内,日内和日间RSD均〈2%。制备的复方脂质体平均粒径162nm,盐酸表阿霉素与紫杉醇的含量分别为0.27、0.83mg/ml;包封率分别为98.6%、95.5%。结论本研究制备的复方脂质体粒径较小,包封率较高,建立的高效液相色谱法可以同时测定盐酸表阿霉素和紫杉醇的含量。

Objective To study the preparation of epirubicin hydrochloride-paclitaxel compound liposomes and to establish a high performance liquid chromatography quantitative method for simultaneous determination of the two drugs.Methods The chromatographic conditions included Venusil MP C 18 column（250 cm×4.6 mm,5 μm）.The mobile phase was a mixture of acetonitrile-methanol-water（36∶ 32∶ 32）with small amounts of phosphoric acid（pH 2.5）.The detection wavelength was at 227 nm and the flow rate was 1 ml/min.Results The retention time of epirubicin hydrochloride and paclitaxel was 4.2 min and 14.8 min,respectively.The regress equation for epirubicin hydrochloride and paclitaxel epirubicin hydrochloride was Y=216 300X-34 525（r= 0.9998,0.1-25 μg/ml）,Y=161 480X-84 107（r=0.9998,0.3-75 μg/ml）,respectively.The average recovery of epirubicin hydrochloride and paclitaxel was between 99%-101%.The intra-and inter day RSD was below than 2%.The particle sizes of compound liposomes were 162 nm.The drug content of paclitaxel and epirubicin hydrochloride was 0.83 mg/ml,0.27 mg/ml,respectively,and the encapsulation efficiency was 95.5% and 98.6% for paclitaxel and epirubicin hydrochloride,repectively.Conclusion The compound liposomes have a small particle size and high drug encapsulation efficiency.This liquid chromatography method can be used for quality control of paclitaxel and epirubicin hydrochloride.