Role of residual solvents in the formation of volatile compounds after radiosterilisation of cefotaxime.

Radiation sterilisation is a promising method to sterilise pharmaceutical products. However, this process is accompanied by a modification of odour due to volatile compounds formation. The origin of malodorous compounds produced during solid cefotaxime radiosterilisation has been investigated and several mechanisms are proposed to explain their appearance. Moreover, some quantitative data are given. Analysis of the degradation products was performed using a GC-ITD system with an injection by the static headspace technique. It appeared that some of the radio-induced compounds (such as carbon oxide sulfide and carbon disulfide) came from the degradation of the drug itself, whereas the formation of others required the presence of residual solvents which are volatile impurities already present before irradiation. Acetaldehyde directly came from impurities but the appearance of esters and acetaldehyde O-methyloxime was due to the presence of both cefotaxime and residual solvents together. Thus, the residual solvents play a key role in the radiolysis compounds formation (six of eight require the presence of them) and consequently in the modification of odour as well.