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. 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.