Design, Development, and Validation of a Stability Indicating RP-HPLC Method for Determination of Diazoxide and Organic Impurities in an Oral Suspension Formulation Using AQbD Approach

Abstract

An RP-HPLC method for the determination of diazoxide content and organic impurities from an oral suspension formulation was established and successfully validated. AQbD was applied to develop this stability-indicating assay method. By optimizing three main factors – buffer pH, organic modifier ratio and flow rate – through CCD, a scientifically and statistically valid MODR was determined. Selectivity was improved by choosing biphenyl as the stationary phase since it facilitates the formation of better aromatic interactions between the analytes, resulting in RRs > 2.0 between diazoxide and its impurities. Forced degradation under acidic, basic, oxidative, thermal and photolytic conditions verified the stability-indicating potential of the developed method, with mass balance maintained at 98–102% level. The study also included a detailed validation process in accordance with ICH Q2 (R2) and a lifecycle-based analytical control strategy was formulated, as stipulated by ICH Q14. Results obtained from method validation were within acceptable limits for the MODR with respect to linearity (r² ≥ 0.9996), percent RSD < 2.0%, and 98.7-101.4% accuracy. Overall, the developed assay procedure is ideal for quality control, stability and regulatory purposes for diazoxide oral suspension formulations.