The research of the composition of substances migrating from plugs based on bromo-butyl rubber into drugs using high-resolution analytical methods

摘要

Pharmaceutical rubber stoppers are use in large quantities to seal sterile forms of infusion and injection drugs and as part of vacuum whole blood sampling tubes for in vitro diagnostics. Obtaining reliable data on the qualitative and quantitative content of both soluble and gaseous substances migrating from plugs and accumulating in drugs and vacuum test tubes for whole blood sampling for in vitro diagnostics is necessary, first of all, to assess the potential risk before using them. Organic substances were identified by their greater content in the studied samples of pharmaceutical rubber stoppers based on bromo-butyl rubber (BBK). High-resolution analytical methods were used: electron impact mass spectrometry, gas chromatography-mass spectrometry, gas chromatography, coupled plasma atomic emission spectroscopy to identify the unknown and complex composition of substances that migrate and accumulate in sterile forms of drugs. The data obtained show that in the process of obtaining BBK, the components of gasoline used as a solvent are brominated, bromine-hydrocarbons are formed, which remain in the bromo-butyl rubber and pass into plugs. The saturated steam sterilization process acts destructively on the polymer base of the plugs - bromobutyl rubber, the migration of volatile organic compounds and the leaching of components from the rubber compound and from BBK - hydrocarbons characteristic of butyl rubber and bromine hydrocarbons, which are direct carcinogens.