Identification, isolation and structural characterization of forced degradation products of sotorasib using advanced analytical techniques

Abstract

Sotorasib is a small molecule inhibitor and approved by USFDA for the treatment of non-small cell lung cancer (NSCLC). In the present study, forced degradation behavior of sotorasib was carried out by utilizing LC-MS/MS technique. As per ICH guidelines, the forced degradation is conducted in various conditions such as acidic, basic, oxidative, thermal and photolytic. A significant degradation was found in acidic, basic and oxidative conditions conversely sotorasib was found relatively stable in thermal and photolytic conditions. In acidic condition, two degradation products such as DP1 and DP3 were isolated. Also, DP3 is the common degradant obtained in both acidic and basic conditions. DP2 is obtained from oxidative conditions. All the isolated degradation products are new and not reported in the literature. All the degradation products are completely characterized by IR, 1H NMR and mass spectroscopy. In conclusion, the scope of study will certainly useful in the regulatory requirements such as physiochemical stability of sotorasib, pharmacokinetic studies and clinical research related.

Keywords

• Sotorasib
• Method development
• Validation
• Forced degradation studies