目的 建立安立生坦原料藥中有關物質的測定方法。方法 采用HPLC法。Waters Atlantis T3色譜柱(250 mm×4.6 mm,5 μm);以0.02%三氟乙酸水溶液-0.01%三氟乙酸乙腈溶液為流動相,進行梯度洗脫;柱溫30 ℃;體積流量1.0 mL/min;自動進樣器控溫5 ℃;檢測波長220 nm。結果 安立生坦與各雜質的分離度良好,雜質Z1、Z2、Z3、Z4、DP1的定量限分別為2.14、2.54、2.44、2.45、2.41 ng,平均回收率分別為102.9%、96.0%、93.1%、104.6%、115.2%,RSD值分別為2.1%、4.6%、2.9%、2.7%、4.9%(n=10)。結論 該方法檢測靈敏度高,精密度好,可以用于安立生坦原料藥中有關物質的質量控制。

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.