Radiosterilization of cefotaxime: investigation of potential degradation compounds by liquid chromatography-electrospray mass spectrometry.

The nonvolatile radiolytic compounds produced by irradiation of cefotaxime were studied by a liquid chromatography-electrospray mass spectrometry method. Full scan LC-MS was first performed in order to obtain the m/z value of the protonated molecules of all detected peaks. LC-MS-MS was then carried out on the compounds of interest. A comparison between the MS-MS spectrum of cefotaxime and those of the radiolytic compounds showed that their fragmentation patterns were very similar suggesting that they were structural analogues of the main drug. The examination of the two main fragmentation pathways also permitted the location of the modified substructures. Moreover, it was shown that some stereoisomers appeared with the irradiation process. The complete fragmentation pattern of cefotaxime was studied by MSn and used to obtain information about the structure of the radiolytic compounds. A complete structure was proposed for four of these

Evaluation of Physical and Chemical Changes in Pharmaceuticals Flown on Space Missions

Efficacy and safety of medications used for the treatment of astronauts in space may be compromised by altered stability in space. We compared physical and chemical changes with time in 35 formulations contained in identical pharmaceutical kits stowed on the International Space Station (ISS) and on Earth. Active pharmaceutical content (API) was determined by ultra- and high-performance liquid chromatography after returning to Earth. After stowage for 28 months in space, six medications aboard the ISS and two of matching ground controls exhibited changes in physical variables; nine medications from the ISS and 17 from the ground met the United States Pharmacopeia (USP) acceptance criteria for API content after 28 months of storage. A higher percentage of medications from each flight kit had lower API content than the respective ground controls. The number of medications failing API requirement increased as a function of time in space, independent of expiration date. The rate of degradation was faster in space than on the ground for many of the medications, and most solid dosage forms met USP standard for dissolution after storage in space. Cumulative radiation dose was higher and increased with time in space, whereas temperature and humidity remained similar to those on the ground. Exposure to the chronic low dose of ionizing radiation aboard the spacecraft as well as repackaging of solid dosage forms in flight-specific dispensers may adversely affect stability of pharmaceuticals. Characterization of degradation profiles of unstable formulations and identification of chemical attributes of stability in space analog environments on Earth will facilitate development of space-hardy medications