目的 建立安立生坦原料药中有关物质的测定方法。方法 采用HPLC法。Waters Atlantis T3色谱柱(250 mm×4.6 mm,5 μm);以0.02%三氟乙酸水溶液-0.01%三氟乙酸乙腈溶液为流动相,进行梯度洗脱;柱温30 ℃;体积流量1.0 mL/min;自动进样器控温5 ℃;检测波长220 nm。结果 安立生坦与各杂质的分离度良好,杂质Z1、Z2、Z3、Z4、DP1的定量限分别为2.14、2.54、2.44、2.45、2.41 ng,平均回收率分别为102.9%、96.0%、93.1%、104.6%、115.2%,RSD值分别为2.1%、4.6%、2.9%、2.7%、4.9%(n=10)。结论 该方法检测灵敏度高,精密度好,可以用于安立生坦原料药中有关物质的质量控制。

Objective To establish a method for determination of related substances in ambrisentan active pharmaceutical ingredients. Methods HPLC method was adopted. The determination was performed on Waters Atlantis T3 column (250 mm × 4.6 mm, 5 μm) with mobile phase consisted of 0.02% trifluoroacetic acid-acetonitrile (containing 0.01% trifluoroacetic acid) with gradient elution. The temperature of column was set at 30 ℃. The flow rate was 1.0 mL/min with automatic injection volume of 5 μL. The detective wavelength was set at 220 nm. Results Ambrisentan and its related substances could be separated completely. The LOQ of the related substances, such as Z1, Z2, Z3, Z4, and DP1 were 2.14, 2.54, 2.44, 2.45, and 2.41 ng, respectively. They all had good linearity. The average recovery were 102.9%, 96.0%, 93.1%, 104.6%, and 115.2% with RSD values of 2.1%, 4.6%, 2.9%, 2.7%, and 4.9% (n=10), respectively. Conclusion The method is sensitive and accurate, and can be used for quality control of related substances in ambrisentan active pharmaceutical ingredients.