Integrated RP-HPLC degradation profiling and Monte Carlo modeling for evaluating gamma-ray radiosterilization suitability of imidazole antifungals

This study introduces an integrated approach combining forced degradation analysis and Monte Carlo gamma modeling to assess the radiosterilization suitability of pharmaceutical compounds. Three imidazole antifungals were subjected to controlled UV (365 nm) and oxidative (3 % H 2 O 2 ) stress conditions, and their degradation behavior was quantitatively assessed using validated reversed phase high performance liquid chromatography (RP-HPLC), yielding percentage degradation, rate constants, and half-life values. UV degradation after 3h was highest for lanoconazole (70.97 %), followed by bifonazole (50.80 %) and butoconazole (15.44 %), confirming greater photostability for butoconazole. Under oxidative stress, bifonazole showed the highest resistance, while lanoconazole fully degraded within 12h. MCNPX Monte Carlo simulations revealed enhanced gamma attenuation and localized energy deposition for bifonazole, consistent with its experimental degradation resistance. Kerma and dose-rate analyses supported a balanced energy deposition profile for bifonazole, correlating with its experimental stability. The integration of chemical degradation profiling via RP-HPLC with physical interaction modeling via Monte Carlo simulations offers a predictive, quantitative framework for assessing radiosterilization tolerance. This approach reduces reliance on empirical irradiation trials, enables early identification of the most stable active pharmaceutical ingredients, and supports the optimization of sterilization protocols in pharmaceutical development. This framework enables early identification of radiation-stable APIs, minimizing empirical trials and supporting optimized sterilization strategies without compromising drug efficacy.