摘要
目的：研究建立高效液相色谱法（high performance liquid chromatography,HPLC）测定地拉罗司有关物质的方法。方法：采用CAPCELL PAK C18MGⅡ色谱柱（250 mm×4.6 mm,5μm）,以0.05 mol·L-1磷酸二氢钠溶液（磷酸调至p H 3.5）为流动相A、乙腈为流动相B进行梯度洗脱,检测波长为245 nm,流速为1.0 m L·min-1。结果：地拉罗司与原料、中间体及其他杂质峰分离良好;地拉罗司的线性范围为0.1～40μg·m L-1（R2=0.999 9,n=9）,水杨酸溶液的线性范围为0.2～80μg·m L-1（R2=0.999 9,n=6）,水杨酸酰胺溶液的线性范围为0.1～40μg·m L-1（R2=0.999 7,n=6）,中间体的线性范围为0.1～50μg·m L-1（R2=0.999 9,n=7）;精密度良好,地拉罗司0.1%自身对照溶液重复进样的RSD值为0.35%;分别以水杨酸、水杨酸酰胺和中间体进行回收率试验,平均回收率分别为99.83%（RSD=1.68%）,98.26%（RSD=1.47%）和99.24%（RSD=1.58%）;分别按杂质对照品外标法和主成分自身对照法计算杂质含量,3批样品最大单个杂质均不超过0.07%,总杂质含量不超过0.23%。结论：本方法准确、灵敏、专属性强,能有效地测定地拉罗司中的有关物质。
Objective： To establish a high performance liquid chromatography（ HPLC） method for the determination of related substances in deferasirox. Methods： The separation was performed on the CAPCELL PAK C18MGⅡ column（ 250 mm × 4. 6 mm,5 μm） with a gradient elution,the mobile phase was consisted of phosphate buffer solution（ 0. 05 mol·L^- 1dipotassium phosphate solution, adjusted to p H 3. 5 by phosphoric acid）-acetonitrile. The detection wavelength was set at 245 nm,and the flow rate was 1. 0 m L·min- 1. Results： The main peak was well separated from the peaks of raw materials and intermediate as well as other impurity peaks. The linearity range of deferasirox was 0. 1 - 40 μg·m L^- 1（ R2= 0. 999 9,n = 9）,the linearity ranges of salicylic acid and salicylamide were 0. 2 - 80 μg·m L^- 1（ R2= 0. 999 9,n = 6） and 0. 1 - 40 μg·m L^- 1（ R2= 0. 999 7,n = 6）,and the linearity range of intermediate was 0. 1 - 50 μg·m L^- 1（ R2= 0. 999 9,n = 7）. The precision was good,and RSD of duplicate deferasirox measeurements was 0. 35%. Average recovery of salicylic acid,salicylamide and intermediate were 99. 83%（ RSD = 1. 68%）,98. 26%（ RSD = 1. 47%） and 99. 24%（ RSD = 1. 58%）.Determined by external standard method and the main component self-comparison method,the content of individual impurity in deferasirox was lower than 0. 07%,and that of total impurities was lower than 0. 23%. Conclusion：The method was accurate,sensitive and specific,thus it is suitable for the determination of related substances in deferasirox.
作者
丁文宇
唐克慧
王宇驰
张春然
张静霞
李喆宇
邓思思
DING Wen-yu TANG Ke-hui WANG Yu-chi ZHANG Chun-ran ZHANG Jing-xia LI Zhe-yu DENG Si-si(Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2016年第20期2376-2381,共6页
Chinese Journal of New Drugs
