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Degradation Pathway Proposal, Structure Elucidation, and In Silico Toxicity Prediction of Dapagliflozin Propane Diol Hydrolytic Degradation Products
Chromatographia ( IF 1.2 ) Pub Date : 2020-07-28 , DOI: 10.1007/s10337-020-03938-4
Prashant S. Devrukhakar , M. Shiva Shankar

Dapagliflozin (DAP) is therapeutic agent for diabetes mellitus type II patients with insufficient glycemic control by exercise and diet. Stability-indicating LC–MS method was developed and validated on C8 column and method was able to separate DAP and three major hydrolytic degradation products. Structure elucidation of three major identified hydrolytic degradation products (DPs) and establishment of degradation pathway were executed with the combine application of liquid chromatography-positive mode electrospray ionization tandem mass spectrometry and high-resolution mass spectrometry. Further ProTox-II was used to predict in silico toxicity for each DPs and compared with DAP.

中文翻译:

Dapagliflozin丙二醇水解降解产物的降解途径建议、结构解析和硅胶毒性预测

Dapagliflozin (DAP) 是针对运动和饮食控制血糖不足的 II 型糖尿病患者的治疗药物。在 C8 色谱柱上开发并验证了稳定性指示 LC-MS 方法,该方法能够分离 DAP 和三种主要的水解降解产物。结合液相色谱-正离子模式电喷雾串联质谱和高分辨率质谱,对三种主要鉴定的水解降解产物(DPs)进行了结构解析并建立了降解途径。进一步的 ProTox-II 用于预测每个 DP 的计算机毒性,并与 DAP 进行比较。
更新日期:2020-07-28
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