1: Pharm Res. 2006 Jun;23(6):1343-9. Epub 2006 Jun 8.

Electron beam and gamma radiolysis of solid-state metoclopramide.

Maquille A, Slegers C, Habib JL, Tilquin B.

Unite d'Analyse Chimique et Physico-chimique des Medicaments CHAM 7230,
Universite Catholique de Louvain, Avenue E. Mounier 72, B-1200, Brussels,
Belgium. aubert.maquille@cham.ucl.ac.be

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.

PMID: 16741660 [PubMed - in process]

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