RESUMEN
PURPOSE: Study the radiolysis of solid-state metoclopramide hydrochloride at various absorbed doses. Elucidate the structure of the degradation products to gain information on the radiolysis mechanisms. METHODS: Solid-state metoclopramide samples were irradiated at several doses with gamma rays and high-energy electrons to evaluate the influence of the dose rate. High-performance liquid chromatography with a diode array detector was used to measure the chemical potency as a function of the absorbed dose and to quantify the degradation products. The characterization of degradation products was performed by liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry. RESULTS: The degradation of solid-state metoclopramide after irradiation was negligible. No qualitative or quantitative differences were observed between gamma and electron beam irradiations (no dose rate effect). Four degradation products that were similar to metoclopramide were detected in trace levels (below 0.1% of the drug concentration) and were not unique to irradiation because they were found in lower amounts in unirradiated metoclopramide. The major degradation product formed after radiation was due to the loss of the chlorine atom from the metoclopramide molecule. CONCLUSION: Solid-state metoclopramide is radioresistant from a chemical point of view and therefore could be a suitable candidate for radiosterilization studies by either gamma rays or high-energy electrons.