Study on the Content Analysis Method of Key Intermediates of Vilanterol and Its Related Substances

Abstract

Objective : In order to establish a new HPLC method for the determination of intermediate 5 of vilan-terol and its related substances. Methods : The chromatographic analysis was performed on C18 na-noscopic column (250 × 4.6 mm, 5 μm) with mobile phase acetonitrile (A) - water (B) and isodegree elution (80% A), and the flow rate was 1.0 min∙ mL − 1 . The detection wavelength was 220 nm, and the related substances were separated by preparative or semi - preparative chromatography. The quali t-ative and quantitative analysis of intermediate 5 and its related substances was realized by HPLC and LC - MS analysis. Results : The results showed that the intermediate 5 showed a good linear relationship in a certain concentration range (Y = 38705X + 21.565), the average recovery was 100.61%~104.81%, RSD < 0.2%, and the repeatability was good (RSD < 0.5%). The solution was stable within 12 h (RSD < 2.0%). The content of intermediate 5 and its related substances was determined by this method. The content of intermediate 5 was 98.0%~99.5%, and the total content of m a-jor impurities was 0.3%~0.6%. The impurity I (RT 1.47 min) was determined to be p - toluenesulfonic acid by qualitative structural analysis, and the impurity III (RT 2.82 min) was determined to be intermediate 4. It is the raw material not cleaned in synthesis. Conclusion : This study provides the o-retical and methodological support for process optimization, effective reduction or removal of impurities and quality control of key intermediates.