“Ghost peaks” of ezetimibe: Solution degradation products of ezetimibe in acetonitrile induced by alkaline impurities from glass HPLC vials

Unpredictable degradation of Ezetimibe solutions in pure acetonitrile occurs when they are stored in glass HPLC vials. The occurrence of the two main degradation peaks and one minor peak was unpredictable at the time of each sample preparation and over time, it appeared that approximately 15% of the sample solutions in glass HPLC vials would eventually show the degradation peaks. Once the degradation peaks occurred in a particular vial, typically within 24 h, they would keep growing until reaching a total yield of about 4-5%. Through a comprehensive investigation, it is determined that the solution degradation is caused by a base-catalyzed process, during which ezetimibe undergoes (1) dimerization to form two dimeric impurities, which have not been reported in the literature, and (2) to a less degree, isomerization to produce an isomeric impurity that has been reported before.