加校正因子的主成分自身对照法测定阿托伐他汀钙中杂质D的含量

Determination of the Content of Impurity D in Atorvastatin Calcium with the Corretion Factor

目的建立加校正因子的主成分自身对照法测定阿托伐他汀钙中杂质D的含量。方法采用HPLC,色谱柱为Agilent ZORBAX SB-C8(4.6 mm×250 mm,5μm)和Agilent Eclipse XDB-C8(4.6 mm×250 mm,5μm),流动相A为乙腈-四氢呋喃-柠檬酸盐溶液(3.9 g·L?1一水合柠檬酸溶液用氨水调节p H值至5.0)(21∶12∶67);流动相B为乙腈-四氢呋喃-柠檬酸盐溶液(3.9 g·L?1一水合柠檬酸溶液用氨水调节p H值至5.0)(61∶12∶27),梯度洗脱;检测波长:244 nm;流速为1.5 m L·min?1,柱温35℃;进样量:20μL。通过测定阿托伐他汀钙和杂质D的线性方程,以斜率计算杂质D相对于阿托伐他汀钙的校正因子。结果测得杂质D相对于阿托伐他汀钙的保留时间为1.96,相对校正因子为0.94,采用外标法和加校正因子的主成分自身对照法分别测定3批阿托伐他汀钙中杂质D的含量,2组检测结果无差异。结论用加校正因子的主成分自身对照法测定阿托伐他汀钙中杂质D的含量,方法可行。

OBJECTIVE To establish a method using the correction factor to determine the content of the impurity D in atorvastatin calcium. METHODS An optimal HPLC method was set up to determine the concentration of impurity D in atorvastatin calcium. The column was Agilent ZORBAX SB-C8（4.6 mm×250 mm, 5 μm） and Agilent Eclipse XDB-C8（4.6 mm×250 mm, 5 μm）. The mobile phase A consisted of acetonitrile-tetrahydrofuran-buffer（3.9 g·L-1 citric acid solution adjust with ammonium hydroxide to a p H of 5.0）（21∶12∶67）, mobile phase B consisted of acetonitrile-tetrahydrofuran-buffer（3.9 g·L-1 citric acid solution adjust with ammonium hydroxide to a p H of 5.0）（61∶12∶27）, gradient elute. The detection wavelength was 244 nm and the flow was 1.5 m L·min-1. The column temperature was 35 ℃ and the injection volume was 20 μL. Then, used the slope of linear equation to determine the correction factor between impurity D and atorvastatin calcium. RESULTS The relative retention time between impurity D and atorvastatin calcium was 1.96, and the relative correction factor was 0.94. And there was no difference between the results determined by the external standard method and the self contrast and correction factor method. CONCLUSION The method using the correction factor between substance being examined and impurity to determine the content of impurity D in atorvastatin calcium is available.