STABILITY-INDICATING UPLC METHOD FOR DETERMINATION OF RAMELTEON AND THEIR DEGRADATION PRODUCTS IN ACTIVE PHARMACEUTICAL INGREDIENTS

Abstract

A novel stability-indicating mass compatible gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of purity of Ramelteon drug substance samples in the presence of its impurities and degradation products. The method was developed using Waters Acquity UPLC BEH SHIELD RP18 (100 mm × 2.1 mm, 1.7 µm) column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 230 nm, the run time was 10 min within which Ramelteon and its four impurities were well separated. Ramelteon was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Ramelteon was found to degrade significantly in acidic and slightly in oxidative stress conditions and stable in base, hydrolytic, and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness.