阿齐沙坦原料药有关物质的检查

Related substances determination of azilsartan bulk drug

目的建立阿齐沙坦原料药有关物质检查方法并对其进行质量评价。方法色谱柱采用华谱Unitary-C18(250 mm×4.6 mm,5μm),流动相为磷酸盐缓冲液(1 000 m L中含40 mmol磷酸二氢钾和3 m L三乙胺,磷酸调节p H为3.60)-甲醇(体积比为40∶60),检测波长为227 nm,柱温为30℃,流速为1.0 m L·min-1,进样量为20μL。采用不加校正因子的主成分自身对照法计算有关物质含量。结果在建立的色谱条件下,阿齐沙坦原料药中阿齐沙坦峰和杂质峰之间分离度良好,杂质A在质量浓度0.06~0.72 mg·L^(-1)内线性关系良好(r=0.999 9),平均回收率为100.0%,RSD为1.52%(n=9);杂质B在质量浓度0.18~0.60 mg·L^(-1)内线性关系良好(r=0.999 7),平均回收率为101.5%,RSD为0.83%(n=9)。结论该方法可以用来控制阿齐沙坦原料药的质量。

Objective In order to evaluate the quality of azilsartan bulk drug,two main impurity A and impurity B of azilsartan were synthesized and HPLC method was established to determine the related substances of azilsartan. Methods The HPLC system was equipped with ACCHROMUnitary-C18column（ 250 mm ×4. 6 mm,5 μm） and phosphate buffer solution（ weighing potassium phosphate monobasic 5. 4 g and triethylamine 3 m L,adding 1 000 m L water to dissolve and adjusting the p H to 3. 60 with phosphoric acid）-methanol（ V / V,40：60） as mobile phase. Detection wavelength was set at 227 nm,column temperature was set at 30 ℃,and the flowrate was 1. 0 m L·min^- 1,the injection volume was 20 μL. The method of main component self-compare without correction factor was applied to the calculation of related substances.Results The chromatographic conditions established in this paper shows good separation between azilsartan peak and impurities peak. For impurity A,the linear ranges was 0. 06- 0. 72 mg·L^-1,r = 0. 999 9,and the average recovery was 100. 0%,RSD was 1. 52%（ n = 9）. And for impurity B,the linear ranges was 0. 18-0. 60 mg·L^-1,r = 0. 999 7,and the average recovery was 101. 5%,RSD was 0. 83%（n = 9）. Conclusions The method is sensitive,durability,accurate and can be used for quality control of azilsartan bulk drug.