Development And Validation of a Stability-Indicating RP-HPLC Method For Simultaneous Estimation of Sorafenib and Metapristone in a Synthetic Mixture

Abstract

In this study, a novel, fast, accurate, and stability-indicating Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the dual quantification of Sorafenib and Metapristone in a prepared mixture is developed and validated. A Phenomenex Luna C18 column (250 mm × 4.6 mm, 5 μm) and an isocratic mobile phase consisting of methanol: phosphate buffer: acetonitrile (60:20:20% v/v) at pH 3.2, adjusted with orthophosphoric acid, were used for the chromatographic separation. Detection was carried out at 225 nm while the flow rate was maintained at 0.8 ml/min. Under ideal circumstances, sorafenib and metapristone were eluted at retention periods of 4.1 and 6.7 minutes, respectively. In accordance with ICH Q2(R1) requirements, the method was validated by evaluating forced degradation experiments, specificity, linearity, precision, accuracy, and robustness. For Sorafenib and Metapristone, linearity was established in the range of 2–12 μg/ml and 4–24 μg/ml, respectively, with correlation values of 0.9971 and 0.9978. With %RSD values for intra-day and inter-day fluctuations below 2%, the approach provided exceptional accuracy. Repeatability and intermediate precision investigations confirmed the accuracy, which was 98.00–99.68% for Sorafenib and 98.11–99.58% for Metapristone. Sorafenib's LOD and LOQ were 0.36 μg/ml and 2.64 μg/ml, whereas Metapristone's were 1.19 μg/ml and 3.65 μg/ml. The specificity of the approach was further confirmed by forced degradation investigations conducted in acidic, alkaline, oxidative, thermal, and photolytic environments since the degradation products were effectively isolated from the parent medications. For regular analysis, stability testing, and quality control of formulations of sorafenib and metapristone, this robust technique can be effectively applied.