Predicting the photostability characteristics of active pharmaceutical ingredients using electron paramagnetic resonance spectroscopy.

Objective: The purpose of this study was to determine if electron paramagnetic resonance (EPR) spectroscopy could be used to develop a quick method to predict the longer-term photostability characteristics of active pharmaceutical ingredients (APIs) for use in the early development phase.

Materials And Methods: EPR spectroscopy was used to study the photodegradation of nearly fifty different APIs in the solid state.

Results: Free radical formation was detected in all but three of the APIs studied and singlet oxygen formation was also detected in the presence of five of the APIs tested.

Electron paramagnetic resonance spectroscopy studies of oxidative degradation of an active pharmaceutical ingredient and quantitative analysis of the organic radical intermediates using partial least-squares regression.

Electron paramagnetic resonance (EPR) spectroscopy was used to study the radical species formed during the oxidation of an active pharmaceutical ingredient in the solid state. It was found that the extent of radical generation correlated to the formation of an oxidative degradation product. Multifrequency EPR and electron nuclear double resonance spectroscopy gave additional information on the identity of the organic radical species involved in the oxidation process, and a mechanism was proposed for the degradation, involving the formation of both carbon-centered and peroxy radicals.