Using the Chemistry of Halogenated Rubber Oligomers in Identifying Unknowns in Extractables Studies

It is widely acknowledged that halogenated rubber oligomers constitute a group of compounds frequently encountered both as extractables in controlled extraction studies and, in specific cases, as leachables in pharmaceutical products.
Although there is an ongoing debate upon the toxicity of these compounds, it is indisputable that they act as potent alkylating agents with high reactivity towards certain functional groups. These interactions have been widely observed, resulting in the formation of adducts with various components of the drug products, including active pharmaceutical ingredients (APIs), peptides, proteins, and excipients.
A second observation is that, when performing a controlled extraction study on rubbers using more aggressive solvents such as IPA, Hexane, a potentially more extensive list of “Unknowns” emerges in both GC/MS and LC/MS. The origin of these unknown compounds is not always very clear.
The question that arises from this observation, considering the high reactivity of halogenated rubber oligomers, is whether some of the reported unknowns could potentially be linked to reaction products of rubber oligomers with other rubber ingredients, such as curing agents, activators, accelerators…
Nelson Labs conducted an R&D programme aimed at systematically allowing the reaction of halo rubber oligomers, compounds that are available as analytical standards at Nelson Labs NV, with other rubber ingredients under the typical conditions of rubber curing. The Initial results from this R&D programme will be shared with the audience.