Determination of chemical stability of sitagliptin by LC-UV, LC-MS and FT-IR methods

Abstract

Sitagliptin was stored at high temperature/high humidity, dry hot air, UV/VIS light and different pH. Then, a selective LC-UV method was developed for determination of sitagliptin in the presence of degradation products and for estimation of degradation kinetics. Because parent drugs can react with excipients in final pharmaceutical formulations, stability of sitagliptin was also examined in the presence of excipients of different reactivity, using FT-IR and LC-UV methods. Finally, LC-MS method was used for identification of degradation products of sitagliptin. High degradation of sitagliptin, following the first order kinetics, was observed in strongly acidic, alkaline and oxidative media. The quickest degradation was found in 2 M HCl and 2 M NaOH. In addition, all excipients used in the present study, i.e. fumaric acid, lactose, mannitol and magnesium stearate showed potent interactions with sitagliptin. Some of these interactions were shown without any stress while others were accelerated by high temperature/high humidity and dry hot air, and less by UV/VIS light. Some mechanisms for the observed changes were proposed, i.e. the Michael addition in the presence of fumaric acid and the Maillard reaction in the presence of lactose. In addition, degradation of sitagliptin together with the occurrence of its impurities was stated in a broad range of stress conditions.

Keywords: FT-IR; High temperature/high humidity, dry hot air and UV/VIS light; Interactions with excipients; LC-UV and LC–MS methods; Sitagliptin and stability; pH and kinetics.