Application of Analytical Lifecycle Management and Monte-Carlo Simulation Approach for Development of a Liquid Chromatography Method for Estimation of Nitazoxanide

Abstract

A new liquid chromatography method was established for estimation of nitazoxanide in pharmaceuticals using a contemporary approach of analytical lifecycle management. The lifecycle approach consisted of designing the method utilizing sound science and risk management tools. During the initial studies % acetonitrile, pH and flow rate were found as critical method variables and were subsequently optimized using a Box-Behnken design, and the effects of method variables on critical quality attributes viz. retention time, theoretical plates and tailing factor were analyzed. Further, procedure performance qualification in terms of process robustness performance was evaluated utilizing Monte-Carlo simulation for the studied method variables. Optimized chromatography was performed on a C-18 column (250 mm × 4.6mm I.D., 5 μm particle size) using isocratic mobile phase of acetonitrile: water (pH 3.74), (80:20) flowing at 1.2 mL/min, with detection at 344 nm. Results for validation parameters viz. linearity (1-120 μg/mL), accuracy (>99%) and precision (<2%) advocated method reliability. Implementation of a lifecycle management approach revealed the influence of crucial method variables on quality attributes and provided a platform for continuous method performance improvement by procedure verification exercises. Development of analytical lifecycle management-oriented validated liquid chromatographic method ensured reliable and robust estimation of nitazoxanide in bulk and, pharmaceutical dosage form.