Integrating quantum chemical descriptors and Monte Carlo simulations for analytical quality assurance of antineoplastic agents under gamma sterilization.

contextThe sterilization of antineoplastic agents remains a critical challenge due to the high sensitivity of active pharmaceutical ingredients (APIs) to ionizing radiation. This study proposes a virtual validation protocol (VVP)-introduced here as a conceptual, computational screening framework rather than a regulatory recognized validation procedure-intended to support analytical quality assurance by prioritizing and guiding experimental stability testing rather than replacing it, thereby reducing the reliance on extensive trial-and-error laboratory work. Obtained results identify mercaptopurine as a significant outlier due to the "trap effect" induced by its sulfur-containing structure (Z

methodsThe protocol integrates density functional theory (DFT) and Monte Carlo (MCNPX) simulations. Molecular structures were optimized at the ωB97XD/def2TZVP level to determine spectroscopic behaviors and evaluate chemical reactivity through HOMO-LUMO energy gaps. Simultaneously, radiation interaction parameters were modeled across a 0.015-15 MeV energy range and validated against theoretical XCOM data.