超高效液相色谱法测定多西他赛注射液含量的研究

Determination of the docetaxel content by ultra performance liquid chromatography technology

目的建立快速、准确的超高效液相色谱方法,测定多西他赛注射液中多西他赛的含量,以便对多西他赛药物进行质量控制,保障患者合理用药。方法色谱条件:Hypersll BDS C18色谱柱(2.1×100 mm,3μm),以甲醇-水(55∶45,V/V),流速:0.4 ml/min,柱温30℃,进样量10μl,波长230 nm;配置紫杉醇、多西他赛和多西他赛空白辅料的标准溶液,进行专属性验证;配置系列浓度的多西他赛工作液,以多西他赛质量浓度对多西他赛与紫杉醇的峰面积比值做回归方程,建立多西他赛标准曲线并确定定量下限;配置多西他赛质控样品,每个浓度5份,进行精密度验证;在空白辅料溶液中,加入适量的多西他赛和紫杉醇,配置质控样品,每个浓度6份,进行回收率验证;配置质控样品,每个浓度配制6份,分别放置24 h,反复冻融3次,-20℃放置1周后进样测定,进行稳定性验证;移取适量多西他赛药物溶液配置成质量浓度为3μg/ml供试品溶液,平行配置3份,进样分析,测得多西他赛药物中多西他赛的含量。结果多西他赛在0.06~10μg/ml范围内具有良好的线性关系(R2=0.999 7),经过专属性、精密度、回收率和稳定性验证,符合相关要求,测得3个批次的多西他赛含量分别为99.4%、98.7%和101.5%。结论通过本实验建立的UPLC方法,可以快捷、灵敏地测定多西他赛药物含量。

Objective Ultra performance liquid chromatography（ UPLC） was established to determine the content of docetaxel in docetaxel injection in order to control the quality of docetaxel and to ensure the rational use of the drug. Methods The chromatographic conditions： Hypersll BDS C18 column（ 2. 1 × 100 mm,3 μm）,equilibrated with methanolwater（ 55∶ 45,V/V）,flow rate： 0. 4 ml/min,column temperature： 30 ℃,amount of sample： 10 μl,and the analysis wave length： 230 nm. The standard solution of paclitaxel,docetaxel and docetaxel blanks were mixed,and the specificity was verified. The docetaxel working fluid was set up in a concentration of docetaxel,and the docetaxel standard curve was established by determining the peak area ratio of docetaxel and paclitaxel. The docetaxel Quality control samples,each concentration of 5 copies,for precision verification; in the blank material solution,add the appropriate amount of docetaxel and paclitaxel,configure the quality control samples,each concentration of 6 copies,the recovery rate verification; configuration quality control Samples were prepared at each concentration of 6 parts,were placed for 24 h,repeated freezing and thawing 3 times,-20 ℃ for one week after the injection determination,stability verification; The dosage of docetaxel was dispensed into 3 μg/ml solution,and 3 parts were placed in parallel. The content of docetaxel in docetaxel was measured. Results Docetaxel had a good linearity in the range of 0. 06-10 μg/ml（ R2= 0. 999 7）,which was verified by specificity,precision,recovery and stability,and met the requirements. His race content was 99. 4%,98. 7% and 101. 5%,respectively. Conclusion UPLC method established by this experiment can be used quickly and sensitively to determine the content of docetaxel.