New RP-HPLC Method Development and Validation, Incorporating Quality by Design (QbD) with Force Degradation Study for Alectinib Estimation-A Green Approach

Objectives

The present research work focuses on development and validation of Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) for the estimation of alectinib with force degradation study based on Quality by Design (QbD) analysis.

Materials and Methods

Two-level optimal factorial design has been used for method optimization, using design expert software. The C18 column was used for chromatographic separations at a 265 nm wavelength, 1.00 mL min^⁻¹ flow rate, and the run time was 10 min at ambient temperature. Risk assessment and statistical analysis were performed to demonstrate the significance of design. The assessment of greenness of this study was performed using the AGREE tool.

Results

The validation was carried out using ICH Q2R1 guidelines and results found linearity R²=0.999. Retention Time (RT) was observed at 3.212, the Limit of Detection (LOD), and Limit of Quantitation (LOQ) were found to be 0.3861 μg/mL and 1.1701 μg/mL, respectively. The Relative Standard Deviation (RSD) for intra-day and inert-day precision was found to be 1.5652 and 1.730 respectively. The forced degradation studies results showed alectinib susceptible to acidic, thermal, and photolytic conditions. No degradation was found in alkaline conditions.

Conclusion

The resulting method with QbD and Green approach holds potential application in routine analysis of alectinib.