Abstract
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.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disorder sparked by insulin resistance and dysfunction of the β cells
Type-2 diabetes is generally characterized by increase in the resistant to insulin which leads to higher blood glucose level [1]
Further we have evaluated 2-mercapto imidazole and triazole derivatives as potential TGR5 agonist [17]. 2-((2-(4-(1H-imidazol-1-yl) phenoxy) ethyl) thio)-5-(2-(3,4-dimethoxyphenyl) propan-2-yl)-1-(4-fluoro phenyl)-1H-imidazole (ZY12201) (Fig. 1) is a potent, selective, and orally efficacious TGR5 agonist, having hTGR5 EC50 of 57 pM and mTGR EC50 of 62 pM with a favorable pharmacokinetic properties and demonstrated in-vivo glucose lowering effects in animal models (ED50 of 7.9 mg/ kg and ED90 of 29.2 mg/kg) [10]
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disorder sparked by insulin resistance and dysfunction of the β cells. Type-2 diabetes is generally characterized by increase in the resistant to insulin which leads to higher blood glucose level [1]. Early studies have revealed that about 25% of people who went to the hospital with severe COVID-19 infections had diabetes. Those with diabetes mellitus were more likely to have serious complications and to die from the virus. One reason is that high blood sugar weakens the immune system and makes it less able to fight off infections [3]. Dedicated in memory of chemistry teacher Late Shri Tilak Raj Taneja
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