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

Abstract

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.

Chemical Analysis of Solid-State Irradiated Human Insulin

“…The literature (37) suggests that the absorbed energy is dispersed through the solid matrix which explains why minor chemical changes are induced in molecular solids. In accordance with previous work (17), the amount of volatile products in irradiated solid insulin should be less than 1 ppm so that they are not detected.…”

“…A static headspace sampling method was used (17,23). No difference was observed in the chromatograms before and after irradiation: no new peak was detected and there was no modification of the pre-existing peaks (Fig.…”

Radiation effect studies on anticancer drugs, cyclophosphamide and doxorubicin for radiation sterilization

“…LC/MS studies are very useful in studying the chemical structure of the degradation products (Barabarin et al, 1999). Fig.…”

Determination of organic impurities in pharmaceutical preparations

“…The determination of impurities in medicinal preparations by this method is commonly performed in the static automatic mode [115,117,118]. A sample is placed in a closed vessel, the vessel is thermostatted, and, after attaining the thermodynamic equilibrium between the sample and vapor phase, an aliquot portion of the equilibrium vapor phase is sampled and directly introduced into the separation column.…”