梯度洗脱HPLC法测定阿那曲唑及片中的有关物质

目的: 建立梯度洗脱HPLC法测定阿那曲唑原料药及片中的有关物质. 方法: 采用Welch Ultimate C₁₈色谱柱(4.6 mm×250 mm,5 μm),流动相A为乙腈-水(40: 60),流动相B为乙腈-水(60: 40),线性梯度洗脱,流速1.0 mL · min^-1,柱温35 ℃,检测波长215 nm. 结果: 阿那曲唑与6种中间体、副产物完全分离.各杂质的线性关系良好,平均回收率均在97%~113%之内,重复性RSD为5.1%,检测限为0.02~0.04 μg · mL^-1.有关物质测定结果:异构体为0~0.19%,杂质B为0~0.01%,杂质C为0~0.04%,杂质A为0~0.08%,杂质D为0~0.01%,杂质E为0~0.04%,其他单个最大杂质为0.05%~0.28%,杂质总量为0.06%~0.42%. 结论: 经方法学验证,本法可用于阿那曲唑及片剂中的杂质检测.

Objective :To develop a gradient HPLC method for the determination of related substances in raw materials of anastrozole and its tablets. Methods :The column was Welch Ultimate C₁₈(4.6 mm×250 mm,5 μm).The mobile phase consisted of acetonitrile-water(40: 60)(A)and acetonitrile-water(60: 40)(B)with gradient program.The flow rate was 1.0 mL · min^-1,and the column temperature was 35 ℃.The detection wavelength was 215 nm. Results :Good separation of anastrozole from six intermediates and by-products was achieved.The standard curves of anastrozole and its impurities were rectilinear in the certain range.The average recoveries of impurities ranged from 97% to 113%.The RSD of precision was 5.1%.The detection limits of impurities ranged from 0.02-0.04 μg · mL^-1.The contents of isomer,impurity B,impurity C,impurity A,impurity D,impurity E,other single largest impurity and total impurities were 0-0.19%,0-0.01%,0-0.04%,0-0.08%,0-0.01%,0-0.04%,0.05%-0.28%,and 0.06%-0.42%,respectively. Conclusion :The method accords with the requirement of methodology validation,and can be used for impurity detection of anastrozole.

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