Degradation Pathway Proposal, Structure Elucidation, and In Silico Toxicity Prediction of Dapagliflozin Propane Diol Hydrolytic Degradation Products

被引：0
作者：
Prashant S. Devrukhakar
M. Shiva Shankar
机构：
[1] Vellore Institute of Technology (VIT),School of Advance Sciences
来源：
Chromatographia | 2020年 / 83卷
关键词：
Forced degradation study; Dapagliflozin propanediol; Degradation pathway; Degradation products; Stability indicating method; LC–MS and HRMS;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
页码：1233 / 1245
页数：12
相关论文
共 110 条
[1]  
Matthaei S(2000)Pathophysiology and pharmacological treatment of insulin resistance Endocr Rev 21 585-618
[2]  
Stumvoll M(2012)Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus Diabetes Metab Syndr Obes 5 135-516
[3]  
Kellerer M(2010)Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight Diabetes Obes Metab 12 510-56
[4]  
Haring HU(2013)The role of analytical chemistry in drug-stability studies, TrAC Trends Anal Chem 49 55-374
[5]  
Whaley JM(2013)Liquid chromatography/electrospray ionization tandem mass spectrometric study of milnacipran and its stressed degradation products Rapid Commun Mass Spectrom 27 369-736
[6]  
Tirmenstein M(2012)Identification and characterization of stressed degradation products of metoprolol using LC/Q-TOF-ESI-MS/MS and MSn experiments Biomed Chromatogr 26 720-471
[7]  
Reilly TP(2017)Forced degradation studies of lansoprazole using LC-ESI HRMS and 1H-NMR experiments: in vitro toxicity evaluation of major degradation products J Mass Spectrom 52 459-146
[8]  
Poucher SM(2019)Isolation and structural characterization of degradation products of afatinib dimaleate by LC-Q-TOF/MS/MS and NMR: cytotoxicity evaluation of afatinib and isolated degradation products J Pharm Biomed Anal 166 139-236
[9]  
Saye J(2017)A stability-indicating LC–MS/MS method for zidovudine: identification, characterization and toxicity prediction of two major acid degradation products J Pharm Anal. 7 231-15
[10]  
Parikh S(2018)Proposal of degradation pathway with toxicity prediction for hydrolytic and photolytic degradation products of timolol J Pharm Biomed Anal 154 7-353
12345678910