目的: 对4个品牌聚山梨酯-80药用辅料以及4个厂家多西他赛注射液中的聚山梨酯-80进行组分分析和比较,评价血液中聚山梨酯-80组分差异对其与多西他赛结合能力的影响。方法: 采用Eclipse-XDB C18(150 mm×4.6 mm,3.5 μm)色谱柱,以乙腈-水(50∶50)为流动相A,四氢呋喃为流动相B梯度洗脱;采用HPLC-ELSD检测器对聚山梨酯-80进行组分分析,采用截留分子量为20 kD的纤维素酯透析膜进行血液平衡透析实验;使用SunfireTMC18(150 mm×4.6 mm,5 μm)色谱柱,以水-乙腈为流动相梯度洗脱测定多西他赛,考察聚山梨酯-80与药物的结合能力。结果: 不同品牌的聚山梨酯-80药用辅料以及不同品牌多西他赛注射液中的聚山梨酯-80在组分上存在一定差异;血液平衡透析实验结果显示聚山梨酯-80对多西他赛的结合能力远小于血液成分与药物的结合能力,血液环境下聚山梨酯-80的组分差异对其与多西他赛结合能力的影响不明显;不同厂家多西他赛注射液中聚山梨酯-80对血液中多西他赛的结合能力差异不明显。结论: 不同厂家多西他赛注射液中聚山梨酯-80对药物在血液中的分配没有显著影响,该研究结果较生理盐水中的透析实验结果更具有生物学意义。
Objective: To analyze and compare the components of 4 brands of Tween-80 excipient and of Tween-80 in 4 docetaxel injection products, and also to evaluate the influence of component differences on the binding ability of Tween-80 to docetaxel in the blood. Methods: HPLC-ELSD was employed to analyze the components of Tween-80. Separation was achieved using an Eclipse-XDB C18 column(150 mm×4.6 mm, 3.5 μm) and a gradient elution system with acetonitrile-water (50∶50) as mobile phase A and tetrahydrofunan as mobile phase B. The binding ability of Tween-80 with drugs in blood was investigated by hemo-equilibrium dialysis using cellulose easter memberane with a 20 kD molecular weight cut-off, where the docetaxel was detected by a SunfireTM C18 column (150 mm×4.6 mm, 5 μm) and acetonitrile-water gradient elution system. Results: Some differences in components were observed from different brands of Tween-80 excipient and also from Tween-80 in different brands of docetaxel injection. The result of hemo-equilibrium dialysis experiment showed that the binding ability of Tween-80 to docetaxel was far less than that of blood components and drugs. No significant change, caused by components difference of Tween-80, in binding ability of Tween-80 to docetaxel was found with the blood samples. The difference in the bindling ability of Tween-80 to docetaxel in the blood from different manufacturers of docetaxel injection was not found to be significant. Conclusion: No significant influence on the drug distribution of docetaxel in blood is caused Tween-80 from different manufactures of docetaxel injection. The result of this study is more biologically reliable than the result of the equilibrium dialysis experiment in saline.
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