Analytical Discovery Chemistry, Aragen Life Sciences Pvt. Ltd., IDA Nacharam, Hyderabad, 500076, India.
Department of Chemistry, GITAM School of Science, GITAM Deemed to be University, Visakhapatnam, 530045, Andhra Pradesh, India.
Sci Rep. 2023 Jun 10;13(1):9472. doi: 10.1038/s41598-023-36289-9.
The research elucidates the stress degradation behavior of Ertugliflozin, which is used for the treatment of type-2 diabetics. The degradation was conducted as per ICH guidelines and Ertugliflozin is relatively stable in thermal, photolytic, neutral, and alkaline hydrolysis conditions; however, considerable degradation was detected in acid hydrolysis and oxidative hydrolysis. Degradation products were identified by ultra-high-performance liquid chromatography-mass spectrometry, isolated by semi-preparative high-performance liquid chromatography, and structural characterization using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Total four degradation products were identified and isolated in acid degradation, which are degradation products 1, 2, 3, and 4. Whereas in oxidative conditions, degradation product 5 was identified. All the five degradation products formed are novel, which was not reported earlier. This is the first time documented complete structural characterization of all five degradation products by using a hyphenated analytical technique. High-resolution mass, and nuclear magnetic resonance spectroscopy were used in the present study to get concrete confirmation of degradation products structures. The current method is also used to identify degradation products with shorter runtime in the future.
本研究阐明了用于治疗 2 型糖尿病的厄格列净的稳定性降解行为。降解是按照 ICH 指南进行的，厄格列净在热、光解、中性和碱性水解条件下相对稳定；然而，在酸水解和氧化水解中检测到相当大的降解。通过超高效液相色谱-质谱联用技术鉴定降解产物，通过半制备高效液相色谱法分离，并使用高分辨率质谱和核磁共振波谱法进行结构表征。在酸降解中鉴定并分离出了四个降解产物，分别为降解产物 1、2、3 和 4。而在氧化条件下，鉴定出了降解产物 5。所有形成的五个降解产物均为新化合物，此前未有报道。这是首次使用键合分析技术对所有五个降解产物进行完整的结构表征。在本研究中，高分辨率质谱和核磁共振波谱用于获得降解产物结构的确切确认。该方法还可用于在未来识别具有更短运行时间的降解产物。
