化学
四极飞行时间
色谱法
质谱法
环氧化物水解酶2
体内
表征(材料科学)
四极
环氧化物
鉴定(生物学)
串联质谱法
生物化学
酶
材料科学
物理
生物技术
植物
原子物理学
生物
纳米技术
催化作用
作者
Sanjay Dey,Renuka Biradar,Sayalee Sanjay Mane,KS Anandhu,Agneesh Pratim Das,Subhash Mohan Agarwal,Swapnil J. Dengale
标识
DOI:10.1016/j.jpba.2024.116116
摘要
EC5026 is a novel soluble epoxide hydrolase inhibitor being developed clinically to treat neuropathic pain and inflammation. In the current study, we employed the LC-ESI-Q-TOF-MS/MS technique to identify four in-vivo phase-I metabolites of EC5026 in rat model, out of which three were found to be novel. The identified metabolites include aliphatic hydroxylation, di-hydroxylation, terminal desaturation, and carboxylation. No phase-II metabolites were found. The pharmacokinetic profile of identified metabolites was established after a single oral dose of EC5026 to Wistar rats. The Tmax of the drug and metabolites were found to be in the range of 1-2 hours and 4-12 hours, respectively. The major metabolites M1 and M2 were found to have more than 2-fold (263.87% AUC) and equivalent exposure (96.33% AUC) compared to the parent drug, respectively. Further, the docking study revealed that the mono-hydroxylated and terminally desaturated metabolites possess better binding affinity than the parent drug. Therefore, these metabolites may hold sEH inhibition potential and can be followed through future research.
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