Radiation-induced effects on cefotaxime: ESR study.

As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as sterilization process for medicinal products. Detection and dosimetry of pharmaceuticals radiosterilization is a growing concern to numerous government regulatory agencies worldwide. In this context, it is necessary to find methods distinguishing between irradiated and nonirradiated pharmaceuticals. In the absence of suitable detection methods, our attention was focused on electron spin resonance (ESR) spectrometry. A third generation cephalosporin, cefotaxime, was chosen as model; this antibiotic is a potential candidate for radiation treatment due to its thermosensitivity. While the ESR spectra of a nonirradiated sample presents no signal, a signal, dependent of the irradiation dose, is found in irradiated samples. The number of free radicals was estimated by comparing the second integral from radiosterilized samples and a diphenyl-picrylhydrazyl reference. Estimation of the number of free radicals gives 1.9 x 10(20) radicals mol(-1) at 20 kGy. From this result, the G-value (number of radicals (100eV)(-1)) could be estimated to 0.3. Aside from qualitative detection, ESR spectrometry can be used for dose estimation. When quadratic, exponential or bi-exponential functions are applied to the variation of peak to peak amplitude vs. dose, these functions correlate well with the data. However, it is important to notice that linear function correlates well with the data for doses lower than 20 kGy. Since the radiation dose selected must be always based upon the bioburden of the products and the degree of sterility required (EN 552 and ISO 11137) 25kGy could no longer be accepted as a "routine dose" for sterilizing a pharmaceutical. Doses from 6kGy (ISO 11137) could be investigated and linear regression would appear to be the least expensive route to follow. The free radicals concentration appeared to not decrease during the 57 days of storage; the number generated during the irradiation allows the detection of radiosterilized cefotaxime up to two years after irradiation.