紫杉醇热敏脂质体的制备与质量控制  

Preparation and Quality Control of Thermo-sensitive Paclitaxel Liposomes

作　　者：李志平[1] 赵希青 赵诗情[1,2] 张慧[1] 刘燕[1] 肖若蕾[2] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]湖北科技学院药学院,咸宁437100

出　　处：《医药导报》2014年第11期1486-1490,共5页Herald of Medicine

摘　　要：目的制备紫杉醇热敏脂质体,建立测定其含量、有关物质及溶血磷脂的方法,考察其含量、有关物质、溶血磷脂量以及体外溶血性。方法采用高效液相色谱（HPLC）-紫外法检测制剂含量及有关物质,HPLC-电雾式检测器检测制剂中溶血磷脂单棕榈酰磷脂酰胆碱的量,并对检测方法进行验证;分光光度法测定体外溶血百分率。结果紫杉醇在60.39-181.17μg·m L^-1范围内峰面积与浓度线性关系良好,回收率及精密度实验均符合要求;有关物质测定方法专属性、灵敏度和系统适用性均符合要求;溶血磷脂测定方法的专属性和灵敏度符合有关规定,在1.5-50.0μg·m L^-1范围内峰面积与浓度线性关系良好,回收率、重复性均符合要求;3批自制紫杉醇热敏脂质体的含量在90.0%-110.0%之间,单个杂质含量均〈0.5%,总杂质含量均〈2.0%,体外基本不引起溶血。结论含量、有关物质及溶血磷脂检测方法均可用于紫杉醇热敏脂质体的质量评价,自制紫杉醇热敏脂质体各项指标均符合要求,且质量稳定。Objective To prepare long-circulating temperature-sensitive liposomes with paclitaxel（ LTSLP）,develop methods for determination of paclitaxel,related substances and monostearoyl phosphatidylcholine（ MSPC） in LTSLP,and the haemolysis of LTSLP in vitro. Methods HPLC-UV methods for paclitaxel content and related substances and HPLC-CAD method for MSPC in LTSLP were established and validated. Spectrophotometric method was used to determine hemolysis in vitro. Results There was a good linear relationship between peak area and concentration within the range of 60. 39- 181. 17 μg·m L^-1.Recovery and precision of the method for determination of paclitaxel content met the requirements. Specificity,sensitivity,and system suitability for related substances were consistent with requirements. There was a good linear relationship between peak area and concentration within the range of 1. 5- 50. 0 μg · m L^-1for the determination of MSPC with good specificity,sensitivity and recovery. Paclitaxel contents in three batches of self-prepared LTSLP were between 90. 0% and 110. 0%,single related substances were below 0. 5% and total impurities were below 2. 0%. There was almost no hemolysis in vitro. Conclusion The methods for determining paclitaxel content,related substances and haemolysis can be used to assess the quality of LTSLP. Self-produced LTSLP consistently meet the quality standards.

关 键 词：紫杉醇热敏脂质体 溶血性 色谱法 高效液相 质量控制 

分 类 号：R97[医药卫生—药品] TQ460.6[医药卫生—药学]