Characterization of Ranolazine Degradation Products by Advanced Spectroscopic Techniques

Ranolazine is a widely used antianginal drug indicated for the treatment of chronic stable angina. In the present study, the degradation behavior of ranolazine was evaluated under acidic, alkaline, and oxidative stress conditions in accordance with ICH guidelines. Forced degradation studies demonstrated that ranolazine was susceptible to acid hydrolysis and oxidative degradation, while remaining stable under alkaline conditions. LC–MS analysis revealed the formation of three degradation products under acidic conditions and two degradation products under oxidative conditions. Among the identified degradants, DP-1 was isolated by preparative HPLC and subjected to detailed structural characterization. The structure of DP-1 was elucidated using high-resolution mass spectrometry (HRMS), LC–MS, and one- and two-dimensional NMR spectroscopy, including ¹H NMR 1H NMR, ¹H NMR 13C NMR, COSY, HSQC, and HMBC experiments. Spectroscopic investigations established that DP-1 was formed through acid-catalyzed hydrolysis of the amide linkage followed by demethylation of the methoxy group, resulting in the formation of 2-(4-(2-hydroxy-3-(2-hydroxyphenoxy)propyl)piperazin-1-yl)acetic acid. A comprehensive literature survey indicated that DP-1 has not been described in earlier degradation studies of ranolazine. The findings provide valuable insight into the degradation pathway and stability profile of ranolazine and support impurity profiling, stability assessment, and pharmaceutical quality control.