Stability-indicating RP-HPLC method for palbociclib: validation and stress-degradation kinetics

Abstract

A stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative determination of palbociclib in bulk drug and capsule dosage form. Separation was achieved on a C18 column (250 × 4.6 mm, 5 µm) using an isocratic mobile phase of acetonitrile and 0.02 M potassium dihydrogen phosphate buffer (60:40, v/v; pH 3.2 ± 0.1) at 1.0 mL/min with UV detection at 267 nm. The palbociclib peak eluted at approximately 4.8 min with acceptable system suitability. The method was linear over 0.5–25 µg/mL and demonstrated adequate sensitivity (LOD 0.15 µg/mL; LOQ 0.45 µg/mL). Accuracy and precision complied with typical ICH acceptance criteria, and robustness was confirmed by deliberate variations in flow rate, mobile phase composition, and wavelength. Forced degradation under acidic, alkaline, oxidative, thermal and photolytic conditions confirmed specificity by resolving palbociclib from degradation products. First-order kinetic behavior under acidic and oxidative stress was evaluated using ln(% remaining) versus time. The method is suitable for routine quality control and stability testing in accordance with ICH guidance.