HPLC detection and quantification of radiolytic products of eight beta-blockers irradiated in the solid state and hypotheses on their origins.

PURPOSE: The radiolytic products of eight beta-blockers were studied in order to understand the mechanisms of irradiation of drugs in the solid state. METHODS: The drugs were analyzed by high-performance liquid chromatography coupled to a diode array detector in order to observe the degradation of the main compound after irradiation and in order to study the nonvolatile final products on more concentrated solutions of irradiated drugs. RESULTS: The first test assessed that the main compound was not significantly degraded after gamma irradiation for any of the eight beta-blockers. A more complete study, which consisted on separating the nonvolatile products and on quantifying them, indicated first that the radiolytic products could reach the number of 14 and moreover that some could exceed the 0.1% threshold at 30 kGy. Eventually, radiolytic yields were compared with radical yields previously determined. CONCLUSIONS: The sensitivity of the first test can be discussed. It seems that, to study the feasibility of the radiosterilization, a complete study of the products of degradation is needed. Moreover, no correlation between radical and final products could be established, which denies that the former would be the precursors of the latter

Chemical analysis of solid-state irradiated human insulin.

PURPOSE: To study the chemical modifications induced upon irradiation of solid human insulin at radiosterilization doses and investigate the influence of the absorbed dose on radiolysis. MATERIALS AND METHODS: Volatile radiolytic products were monitored by gas chromatography coupled with mass spectrometry (GC-MS) and non-volatile products by two different high performance liquid chromatography (HPLC) methods: the formation of higher molecular weight proteins was assessed by size exclusion liquid chromatography whereas assays for related compounds and chemical potency tests were carried out using reverse-phase HPLC-UV. Conformational changes were investigated by measurements of circular dichroism. RESULTS: After gamma irradiation at 10 kGy, the recovery of insulin was 96.8%; higher molecular weight proteins accounted for 0.35% (relative peak area) and other related compounds (including A21 desamido insulin) represented 1.29%. No major structural changes and no volatile radiolytic compounds were detected. CONCLUSION: Human insulin samples irradiated in the solid-state at 10 kGy (gamma rays) and 14 kGy (electron-beam) meet the European Pharmacopoeia requirements and can be considered as quite stable towards radiation from a chemical analysis viewpoint

Tackling the paradox: can attaining global research excellence be compatible with local technology development?

This paper uses the case of the IMEC (microelectronics research centre) to examine the compatibility between strategic IPR management of large independent research centres, and regional industrial policy missions given to such centres in return for government funding. In particular, the issue of whether a balance can be found between a necessary drive for international recognition and critical mass of funding, and a policy of IPR valorization towards regional firms is examined. The first section sets out the mission of IMEC and the evolution over time of its strategic approach to building global industrial partnerships based on a sophisticated model of IPR management. Drawing on a recent evaluation, the subject of the second section is the extent to which the results of the industrial and exploratory research activities of IMEC are then commercialized in local Flemish industry. The concluding section offers policy conclusions in terms of the instruments and objectives which public policy makers can apply to maximize the local impact of large globally operating research centres