Sojitra Chandrakant, Dholakia Chintan, Sudhakar Padmaja, Singh Kumar K, Agarwal Sameer
API Division, Cadila Healthcare Limited, Sarkhej-Bavla N.H. No. 8 A, Changodar, Ahmedabad, 382 210 India.
Department of Chemistry, Faculty of Science, M.S. University of Baroda, Baroda, 390 002 India.
SN Appl Sci. 2021;3(6):660. doi: 10.1007/s42452-021-04660-y. Epub 2021 May 25.
Forced degradation study is a systemic characterization of degradation products of active pharmaceutical ingredient (API) at conditions which posses more harsh environment that accelerates degradation of API. Forced degradation and stability studies would be useful in selection of proper, packaging material and storage conditions of the API. These are also useful to demonstrate degradation pathways and degradation products of the API and further characterisation of the degradation products using mass spectrometry. TGR5 is a G protein-coupled receptor, activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The potent and orally bioavailable TGR5 agonist, ZY12201, shows activation of TGR5 which increase secretion of GLP-1 and help in lowering blood glucose level in animal models. Hence it is necessary to establish and study degradation pathway and stability of API for better handling and regulatory approval. Force degradation studies of ZY12201 have shown presence of one oxidative impurity during oxidative degradation in HPLC analysis. The oxidized product is further characterized by LC-MS to elucidate structure of impurity and characterize its degradation pathway.
The online version contains supplementary material available at 10.1007/s42452-021-04660-y.
强制降解研究是在比加速活性药物成分（API）降解的更恶劣环境条件下，对API降解产物进行的系统表征。强制降解和稳定性研究对于选择合适的API包装材料和储存条件很有用。这些研究对于证明API的降解途径和降解产物，以及使用质谱对降解产物进行进一步表征也很有用。TGR5是一种G蛋白偶联受体，其激活可促进胰高血糖素样肽-1（GLP-1）的分泌并调节胰岛素分泌。强效且口服生物可利用的TGR5激动剂ZY12201显示出TGR5的激活，这会增加GLP-1的分泌，并有助于降低动物模型中的血糖水平。因此，有必要建立并研究API的降解途径和稳定性，以便更好地处理和获得监管批准。ZY12201的强制降解研究表明，在高效液相色谱分析的氧化降解过程中存在一种氧化杂质。通过液相色谱-质谱联用对氧化产物进行进一步表征，以阐明杂质的结构并表征其降解途径。
在线版本包含可在10.1007/s42452-021-04660-y获取的补充材料。
