Attempts at correlation of the radiolytic species of irradiated solid-state captopril studied by multi-frequency EPR and HPLC.

The purpose of this study was to provide insight into the processes that occur after the irradiation of solid-state drugs. Electron paramagnetic resonance (EPR) experiments were performed at two different frequencies, X-band (about 9.5 GHz) and Q-band (about 34 GHz), to identify the radicals present in irradiated captopril. The results confirmed that an irradiated drug can trap several main radicals. Moreover, the radical composition varied as a function of the treatment. In addition, non-volatile final products were studied by liquid chromatography coupled to UV and to mass spectrometry (LC-MS). The variation of the radical composition did not influence the profile of the final products; this appears to indicate that, in the case of captopril, the trapped radicals observed by EPR are not the main precursors of the final products. Finally, high-performance liquid chromatography data appear to indicate that radiosterilization of captopril is feasible.

Determination of radical yields in solid-state drugs as one technique to identify drugs that will withstand radiosterilization: radioresistance of beta blockers.

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.

Sensitivity of whole human teeth to fast neutrons and gamma-rays estimated by L-band EPR spectroscopy.

This paper reports the first attempt to use L-band spectroscopy for estimating the sensitivity of whole teeth to fast neutrons and gamma-rays. Three teeth were successively irradiated first with fast neutrons with a wide energy spectrum (mean energy around 30 MeV) up to approximately 160 Gy and then with gamma-rays up to approximately 14 Gy. After each irradiation, L-band (approximately 1 GHz) EPR spectra of each whole tooth surrounded by the surface-coil resonator were recorded, yielding a single composite line principally due to CO2- and native radicals. The sensitivities are estimated by the slopes of the linear dose response curves of the dosimetric CO2- radicals. The ratios of the gamma/neutron sensitivities were found to be in the range 8-9 (+/- 2) for the three teeth.