Development and validation of a robust RP-HPLC method for Landiolol using analytical quality by design

A systematic Analytical Quality by Design based reverse-phase high-performance liquid chromatography method was successfully developed and validated for the quantification of Landiolol in pharmaceutical formulations. The method optimization employed Central Composite Design with Analysis of Variance revealing a statistically significant model (F-value = 11.60, p = 0.0003). The optimized chromatographic conditions included an Inertsil ODS column (150 × 4.6 mm, 5 μm), mobile phase comprising 55% sodium dihydrogen phosphate and 0.2% orthophosphoric acid, f low rate of 1.25 mL/min, injection volume of 15 µL, and detection wavelength of 240 nm, yielding a retention time of 2.70 min. The validated method demonstrated excellent system suitability with USP tailing factor of 1.0, plate count of 10,925, and similarity factor of 98.4%. System precision showed exceptional reproducibility with %RSD of 0.3%, while linearity was established over the concentration range with R² = 0.9999. Accuracy studies revealed recoveries between 100.8 and 101.1% across 50%, 100%, and 150% levels. Forced degradation studies indicated Landiolol stability under thermal (3% degradation) and oxidative conditions (4% degradation) but significant photolytic degradation (9%). The greenness assessment yielded a score of 0.88, confirming environmental sustainability. This robust, precise, and environmentally conscious analytical method complies with regulatory guidelines for routine quality control and pharmaceutical analysis of Landiolol formulations.
Keywords Analytical quality by design, RP-HPLC, Landiolol, Method validation, Central composite design