Kovačić Jelena, Amidžić Klarić Daniela, Turk Nikša, Krznarić Željko, Mornar Ana
Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Department of Gastroenterology, University Hospital Centre, Zagreb, Croatia.
Heliyon. 2024 Jul 4;10(13):e34066. doi: 10.1016/j.heliyon.2024.e34066. eCollection 2024 Jul 15.
Etrasimod, a novel selective sphingosine-1-phosphate receptor modulator, was recently approved by the U.S. Food and Drug Administration and the European Medicinal Agency for the treatment of moderately to severely active ulcerative colitis in adults. In this research, the forced degradation study as an integral part of drug product and packaging development, which generates data on degradation mechanisms, is published. The development and validation of the stability-indicating method using a superior high-performance liquid chromatography technique coupled with a diode array detector and tandem mass spectrometer was performed to support the forced degradation study and monitor the formation of degradation products. Etrasimod demonstrated good stability under elevated temperature and basic stress conditions, while acidic hydrolysis, oxidative, and photolytic degradation produced eight degradation products. The knowledge of degradation products will be useful in the long-term stability study for establishing the acceptance criteria of etrasimod as a drug substance and dosage form during quality control and stability assessment. The eco-friendliness of the developed forced degradation procedure was evaluated using various greenness appraisal tools. The green metric tools showed that the forced degradation procedure obeys eco-friendly conditions.
艾曲莫德是一种新型的选择性1-磷酸鞘氨醇受体调节剂，最近已获美国食品药品监督管理局和欧洲药品管理局批准，用于治疗成人中度至重度活动性溃疡性结肠炎。在本研究中，作为药品和包装开发不可或缺的一部分的强制降解研究已发表，该研究生成了降解机制的数据。采用一种结合二极管阵列检测器和串联质谱仪的高效液相色谱技术进行稳定性指示方法的开发和验证，以支持强制降解研究并监测降解产物的形成。艾曲莫德在高温和碱性应激条件下表现出良好的稳定性，而酸性水解、氧化和光解降解产生了8种降解产物。降解产物的相关知识将有助于长期稳定性研究，以便在质量控制和稳定性评估过程中确定艾曲莫德作为原料药和剂型的验收标准。使用各种绿色评估工具对所开发的强制降解程序的生态友好性进行了评估。绿色指标工具表明，强制降解程序符合生态友好条件。
