ISOLATION AND STRUCTURAL ELUCIDATION OF DEGRADATION PRODUCTS OF RANOLAZINE

Degradation studies are important to know the potentials degradation products and to develop a stability indicating method. Ranolazine active pharmaceutical ingredients subjected to in detailed forced degradation study using several stressing agents (HCl, NaOH, H₂O₂). Degradation products of Ranolazine under hydrolytic and oxidative stress conditions were identified, and their stabilities were assessed. Three degradation products were formed when the drug was subjected to acid stress and two products were formed in oxidative stress condition. Ranolazine was stable to base hydrolysis. The degradants were separated on a C-8 column employing preparative HPLC using gradient elution. The structures of all the five degradation products (DP-1, DP-2, DP-3, DP-OX1, and DP-OX2) were established by extensive 1D (¹H, ¹³C) and 2D (COSY, HSQC and HMBC) NMR spectroscopic studies and mass spectra. The products were identified as 2-(4-(2-hydroxy-3-(2-hydroxyphenoxy) propyl) piperazine-1-yl) acetic acid (DP-1), 2-(4-(2-hydroxy-3-(2-methoxy phenoxy) propyl) piperazine-1-yl) acetic acid (DP-2), N-(2,6-dimethylphenyl)-2 -(4-(2-hydroxy-3 (2-hydroxyphenoxy) propyl) piperazine-1-yl) acetamide (DP-3), 1-(2-((2,6-dimethylphenyl)amino)-2oxoethyl)-4-(2-hydroxy-3-(2-methoxy phenoxy) propyl) piperazine 1, 4-dioxide (DP-OX1), 4-(2-((2, 6 dimethyl phenyl) amino)-2-oxoethyl)-1-(2-hydroxy-3-(2-methoxy phenoxy) propyl) piperazine 1-oxide (DP-OX2). All the degradants reported here are novel except DP-OX1.