QbD-Based Analytical Method Development and Validation for Quantification of Lobeglitazone in Pharmaceutical Formulation.

Abstract

A systematic, accurate, and robust reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative estimation of Lobeglitazone in bulk and tablet dosage form by applying a Quality by Design (QbD) approach. A Central Composite Design (CCD) was employed to optimize the chromatographic method by evaluating the effects of two critical method parameters—methanol concentration in the mobile phase and flow rate—on three analytical responses: retention time, peak area, and theoretical plates

The chromatographic separation was carried out using a C18 column (250 × 4.6 mm, 5 µm) with a mobile phase comprising methanol and 0.1% orthophosphoric acid in the ratio of 57.49:42.51 v/v, at a flow rate of 0.91 mL/min, and detection at 248 nm. The method was validated in accordance with ICH Q2(R1) guidelines and showed excellent linearity (5–25 µg/mL, r² = 0.999), precision (intra- and inter-day %RSD < 2%), accuracy (recoveries between 98–102%), and specificity. The robustness of the method was assessed through small deliberate changes in chromatographic conditions, confirming method reliability.The optimized method was applied for assay of tablet formulations and was found suitable for routine quality control analysis. The application of the QbD approach ensured systematic development with better method understanding and enhanced regulatory compliance.