The extent of physico-chemical changes induced by irradiation of cefazolin sodium was investigated. The methods used were potency determination, impurity profile, colour measurements and pH measurements. The potency of irradiated samples at 25 kGy was 4 9 2% lower than that of the non irradiated ones. The total amount of related substances increased from 0.72 90.01% in the non irradiated samples to 4.9 9 0.7% in the samples irradiated at 25 kGy. Most of the peaks showed trace amounts ( B 0.01%), the largest one represented 1.2 9 0.5% of the total related substances. Only two peaks were identified by chromatography: the methyl-1,2,3-thiazol-2 thiol-5 and the 7-aminocephalosporanic acid. The latter related substance is only produced by the irradiation of cefazolin sodium. The pH values of the samples were within the specifications of the European Pharmacopoeia. The colour of the cefazolin sodium powder changed from white to yellow upon irradiation. The yellow colour persisted after the dissolution of the powder. Most of the tests carried out met the Pharmacopoeia's specifications, except the one concerning the colour of the solution.

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Radio-induced modifications in proteins have been studied using several techniques. Electron paramagnetic resonance (EPR) was used to characterize free radicals, and analysis methods (high-performance liquid chromatography, capillary electrophoresis) were employed to visualize final degraded forms. Whereas EPR indicates that perthiyl radicals are formed, analysis does not detect any compound in which such bonds would be broken. Since EPR signals decay with time, it is concluded that rearrangements occur at subsequent steps, in which the solvent used during the analysis might play a role.

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This article describes a simple preliminary test to determine whether a drug is sufficiently radioresistant to withstand radiosterilization. The test is based on the electron spin resonance (ESR) detection of radicals produced after irradiation of a solid-state drug, assuming that these radicals are the precursors of the final products detected after dissolution of the drug. A calibration curve has therefore been established by measuring ESR spectra of l-alanine irradiated at different doses. The response factor to quantify the radicals is the normalized double integration (DI) of the whole first-derivative ESR spectrum. The curve gives the relationship between the normalized DI and the number of radicals. Eight beta blockers have been chosen and their radical yield determined. This is the first time that several different drugs of the same pharmacological group have been studied and compared. The results obtained are similar for seven of the eight beta blockers; the mean G value (excepted for nadolol) is 3 x 10(-9) mol/J. This means that beta blockers are radioresistant. The two most radiosensitive drugs (nadolol and esmolol hydrochloride) were also studied by high-performance liquid chromatography (HPLC). No significant loss of the active compound was detected, which confirms this radioresistant property. Moreover, no change in color or smell was observed. Using ESR and HPLC, beta blockers were identified as potential candidates for radiosterilization.