Dual Organic Modifier, Solid Core Technology and Quality by Design Based Tripartite Synergistic Model for Development and Validation of Stability Indicating Method by Reverse Phase-High Performance Liquid Chromatography for Assay and Impurities of Etoricoxib Tablets

Abstract

Tripartite synergistic model of solid core technology, dual organic modifiers and combined mixture design was implemented to achieve combined assay and related substances method by reverse phasehigh performance liquid chromatography with short run time, enhanced sensitivity and improved resolution between multiple impurity peaks. pH of mobile phase, ternary mobile phase composition and high performance liquid chromatography column temperature are experimented as variable parameters. Acetonitrile and isopropyl alcohol mixture was experimented as dual organic modifier. Special focus was given to detailed methodology of dealing with elution order changes by assigning negative sign for resolution. Separation of etoricoxib and related impurities was evaluated as a case study to prove this concept. The method was developed with Ascentis® Express C18, 150×4.6 mm, 2.7 μ column. Mobile phase comprised of buffer (0.1 % v/v ortho phosphoric acid, pH 3.6), acetonitrile and isopropyl alcohol (65.3:29:5.7 v/v) with a flow rate of 1.0 ml/min and ultraviolet detection at 285 nm. Forced degradation studies revealed that the method was stability indicating, suitable for both assay and impurities of drug product. The recoveries for impurities and assay were found to be in the range of 94.0 %-111.0 % and 97.9 %-101.8 %, respectively. Linearity was established for impurities and assay in the range of 0.25-2.0 μg/ml and 125-750 μg/ml, respectively. The method was validated as per international conference on harmonisation guidelines. The method can be successfully employed for determination of assay and impurities of etoricoxib in bulk drugs and formulations.