School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
Zhongcai Health (Beijing) Biological Technology Development Co., Ltd., Beijing 101500, China.
Eur J Pharm Sci. 2018 Jan 1;111:458-464. doi: 10.1016/j.ejps.2017.10.028. Epub 2017 Oct 21.
Trelagliptin succinate is a dipeptidyl peptidase IV (DPP-4) inhibitor which is used as a new long-acting drug for once-weekly treatment of type 2 diabetes mellitus (DM). In the present study, a rapid, sensitive and accurate high-performance liquid chromatography (HPLC) method was developed and validated for separation and determination of trelagliptin succinate and its eight potential process-related impurities. The chromatographic separation was achieved on a Waters Xselect CSH™ C (250mm×4.6mm, 5.0μm) column. The mobile phases comprised of 0.05% trifluoroacetic acid in water as well as acetonitrile containing 0.05% trifluoroacetic acid. The compounds of interest were monitored at 224nm and 275nm. The stability-indicating capability of this method was evaluated by performing stress test studies. Trelagliptin succinate was found to degrade significantly in acid, base, oxidative and thermal stress conditions and only stable in photolytic degradation condition. The degradation products were well resolved from the main peak and its impurities. In addition, the major degradation impurities formed under acid, base, oxidative and thermal stress conditions were characterized by ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). The method was validated to fulfill International Conference on Harmonisation (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness. The developed method in this study could be applied for routine quality control analysis of trelagliptin succinate tablets, since there is no official monograph.
琥珀酸曲格列汀是一种二肽基肽酶-4（DPP-4）抑制剂，被用作治疗 2 型糖尿病（DM）的每周一次长效新药。本研究开发并验证了一种快速、灵敏、准确的高效液相色谱（HPLC）方法，用于分离和测定琥珀酸曲格列汀及其八种潜在的工艺相关杂质。色谱分离在 Waters Xselect CSH™ C（250mm×4.6mm，5.0μm）柱上实现。流动相由 0.05%三氟乙酸水溶液和含 0.05%三氟乙酸的乙腈组成。在 224nm 和 275nm 处监测目标化合物。通过进行稳定性研究评估了该方法的指示能力。琥珀酸曲格列汀在酸、碱、氧化和热应激条件下显著降解，仅在光解降解条件下稳定。降解产物与主峰及其杂质完全分离。此外，在酸、碱、氧化和热应激条件下形成的主要降解杂质通过超高效液相色谱与线性离子阱-Orbitrap 串联质谱（UHPLC-LTQ-Orbitrap）进行了表征。该方法经过验证，符合国际人用药品注册技术协调会（ICH）的要求，该验证包括专属性、线性、检测限（LOD）、定量限（LOQ）、准确性、精密度和稳健性。由于没有官方专论，本研究开发的方法可用于琥珀酸曲格列汀片剂的常规质量控制分析。
