Aubert Maquille

Electron-beam and gamma radiolysis of solid-state metoclopramide

PurposeStudy 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.MethodsSolid-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.ResultsThe 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.ConclusionSolid-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.

Cryo-irradiation as a terminal method for the sterilization of drug aqueous solutions

The aim of this study is to evaluate the specificities of the irradiation of drugs in frozen aqueous solution. The structures of the degradation products were determined to gain insight into the radiolysis mechanisms occurring in frozen aqueous solutions. Metoclopramide hydrochloride and metoprolol tartrate were chosen as models. The frozen solutions were irradiated at dry ice temperature by high energy electrons at various doses. The drug purity (chemical potency) and the radiolysis products were quantified by HPLC-DAD. Characterization of the degradation products was performed by LC-APCI-MS-MS. The structures of the radiolysis products detected in irradiated frozen aqueous solutions were compared to those detected in solid-state and aqueous solutions (previous studies). For both metoclopramide and metoprolol, solute loss upon irradiation of frozen aqueous solutions was negligible. Five radiolysis products present in traces were identified in irradiated metoclopramide frozen solutions. Three of them were previously identified in solid-state irradiated metoclopramide crystals. The two others were formed following reactions with the hydroxyl radical (indirect effect). Only one fragmentation product was observed in irradiated metoprolol frozen solutions. For both drugs, radiosterilization of frozen solutions, even at high doses (25 kGy), was found to be possible.

Chemical analysis applied to the radiation sterilization of solid ketoprofen

The aim of this work is to investigate the feasibility of radiation sterilization of ketoprofen from a chemical point of view. Although irradiated ketoprofen has already been studied in the literature [Katu[sbreve]in-Ra[zbreve]em et al., Radiat. Phys. Chem. 73 111–116 (2005)], new results, on the basis of electron spin resonance (ESR) measurements and the use of hyphenated techniques (GC-MS and LC-MS), are obtained. The ESR spectra of irradiated ketoprofen consists of four unresolved resonance peaks and the mean G-value of ketoprofen is found to be 4±0.9 nmoles/J, which is very small. HPLC-UV analyses indicate that no significant loss of ketoprofen is detected after irradiation. LC-MS-MS analyses show that the structures of the non-volatile final products are similar to ketoprofen. Benzaldehyde is detected in the irradiated samples after dynamic-extraction GC-MS. The analyses show that ketoprofen is radioresistant and therefore might be radiosterilized.