A Novel Analytical Method Development and Validation for Impurity Profiling of Lobeglitazone Sulfate in Bulk Drug Substance by RP HPLC

Background : In this study, a novel and robust reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantification of Lobeglitazone sulfate and its related impurities Impurity A and Impurity B in bulk drug substance. Extensive chromatographic trials were performed using various mobile phases, columns, and gradient programs to optimize separation efficiency. Results : The finalized RP-HPLC method employed a Platisil C18 column (150×4.6 mm, 3 µm) with gradient elution of KH₂PO₄ buffer (pH 4.0) and methanol, detected at 247 nm. The method showed excellent system suitability with sharp, symmetrical peaks, high theoretical plates, tailing factors < 2, and resolution > 2. Validation as per ICH guidelines confirmed specificity, linearity, precision, accuracy, robustness, and sensitivity. Linearity was achieved for Lobeglitazone (30–150 µg/mL), Impurity A (3–15 µg/mL), and Impurity B (2–10 µg/mL) with R² > 0.999. Recovery ranged between 98–102%, and %RSD < 2% demonstrated high precision. Forced degradation studies established the method as stability-indicating, effectively separating degradation products under acid, base, peroxide, thermal, and photolytic conditions, with maximum degradation (~7–8%) under peroxide stress. Conclusion : Overall, the developed RP-HPLC method is specific, precise, accurate, robust, and stability-indicating, making it suitable for routine quality control and stability testing of Lobeglitazone sulfate and its impurities in bulk drug substance.