Abstract

The elafibranor (ELB) is a new drug approved by the US FDA to treat primary biliary cholangitis in adults, in combination with ursodeoxycholic acid (UDCA). In accordance with International Council for Harmonisation principles, the stress study of drug substances is very important as per Q1 guidelines. This research mainly focused on the ELB’s degradation behavior under stress circumstances, such as thermal, oxidative, photolytic, and hydrolytic (acid, base, and neutral) environments. It was observed that the drug ELB degraded noticeably in base hydrolysis (11.27%), oxidation (17.85%), and photolytic (7.10%) conditions. A newly optimized HPLC approach was used, using an XBridge BEH C18 column (150 × 4.6 mm, 3.5 μm) to isolate and quantify the degradation products. During the active pharmaceutical ingredient degradation, ELB was broken down into two products: DP-1 and DP-2. In oxidation and photolytic conditions, ELB also degraded into two new degradation impurities, DP-3 and DP-4. The degradation products are identified, and possible structures are established by employing the Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry fragmentation pattern. To our knowledge, no one has published degradation studies of ELB so far. This study may help with drug formulations for clinical studies and routine analysis.

Key words: Elafibranor, Forced degradation, Degradation products, ICH guidelines, LC-ESI-MS/MS