Chemical stability of esomeprazole in biorelevant bicarbonate buffer and an exploratory study for specific degradation products

This study aimed to evaluate the impact of biorelevant bicarbonate buffer solutions (BCB) on drug degradation relative to phosphate buffer solutions (PPB). Esomeprazole (ESM) was selected as a model compound. Stability studies were conducted at 37 °C using 10 mM BCB and 31 mM PPB (both at pH 5.5; buffer capacity (β) = 4.0 mM/pH; ionic strength (I) = 0.14 M). Degradation products were quantified at 4 time points by HPLC. No significant difference was observed in the degradation rate constant of ESM between BCB and PPB. However, LC-MS analysis revealed a distinct tendency that two degradation products with m/z values of 330 and 298 were more abundant in BCB than in PPB. The putative structures of these degradation products matched the previously reported compounds. These findings suggest that buffer species can influence degradation pathways even under equivalent β and I. Consequently, the use of biorelevant buffer systems is essential for accurate assessments of degradation products.