Degradation Kinetic Study and Mechanistic Interpretation of Hydrolysis of Pidotimod by LC-MS/MS: A QbD Assisted Stability Indicating Method Development

The stability of pidotimod was investigated in this study under ICH-recommended stress degradation conditions. To explore the degradation kinetics of pidotimod, a QbD assisted stability indicating assay method was designed and validated according to ICH Q2 (R1) guidelines. The impacts of hydrogen and hydroxide ions were explored, with a focus on the kinetics of pidotimod hydrolytic degradation to identify the rate laws, which were parameterized using linear regression analysis. The degradation product (DP2) was formed as a major degradation product of hydrolysis. Four known and one unknown degradation product were formed under hydrolysis. Degradation of pidotimod in acid and base degradation follows first-order reaction kinetics while the neutral degradation follows zero-order reaction kinetics. The observed degradation products of pidotimod under hydrolytic degradation were identified by LC-MS/MS analysis and a mechanism of hydrolysis is proposed.