苯甲酸阿格列汀原料药的有关物质及含量测定

Determination of alogliptin benzoate and its related substances

目的建立RP-HPLC法测定苯甲酸阿格列汀原料药的含量及有关物质。方法采用Thermo ODS-2 HYPERSIL色谱柱（250 mm×4.6 mm,5μm）,以乙腈-体积分数为0.1%甲酸水溶液（用三乙胺调p H值为3.0）为流动相,流速为1.0 m L·min^-1,检测波长为278 nm,柱温为30℃。结果在含量测定色谱条件下,阿格列汀在质量浓度8~80 mg·L^-1内与峰面积呈良好线性关系（r=0.999 8,n=5）,平均回收率为99.9%（n=9）;在有关物质测定色谱条件下,有关物质A、B、C、D和E在质量浓度0.1~2.0 mg·L^-1内与峰面积呈良好的线性关系（r在0.999 6~0.999 8内,n=6）;有关物质A、B、D和E含量均小于0.25‰,有关物质C含量小于0.4‰。结论该方法准确、专属性强,为苯甲酸阿格列汀原料药的质量控制提供了依据。

Objective To establish an RP-HPLC method for the determination of alogliptin benzoate and its related substances. Methods The method was performed on a Thermo ODS-2 HYPERSIL column（ 250 mm × 4. 6 mm,5 μm） using a mobile phase consisting of acetonitrile as the mobile phase A,0. 1% formic acid（ adjust the p H value to 3. 0 with triethylamine） as the mobile phase B. The flowrate was1. 0 m L·min- 1,the detection wavelength was set at 278 nm,and the column temperature was set at 30 ℃.Results For the content determination,a linearity between the area of alogliptin and its concentration was achieved in the range of 8-80 mg·L- 1（ r = 0. 999 8,n = 5）. The average recovery was 99. 9%（ n = 9）. For the impurities determination,the standard curves of impurities A-E were linear in the range of 0. 1-2. 0 mg·L- 1（ r = 0. 999 6-0. 999 8,n = 6）. The contents of impurities A,B,D,E were below0. 25‰,the content of impurity C was below0. 4‰ in the rawmaterial. Conclusions The method is accurate,specific,and provides a reference for the quality control of alogliptin benzoate.