Compounds introduced during synthesis including starting materials, intermediates and by-products may be carried through the synthesis to become impurities in the final product. If these are predicted or known to be mutagenic then they are subject to regulation under the ICH M7 guidelines. These guidelines allow for a chemistry-based argument that the impurity will not survive the synthetic route and evidence of its absence may then not be necessary. A prototype tool has been developed that allows for the analysis of large-scale reaction data such as those available from text mining or from electronic lab notebooks. This poster will present example analyses using text-mined reactions from the United States Patent Office patent applications and grants provided by NextMove software. Reactions are automatically categorised via mapping and generation of a reaction core representing the atom and bond changes occurring within a single-step reaction. These reaction cores can be used to generate clusters of reactions sharing common mechanisms without the need for a named reaction. Reaction networks can be generated as tree structures, organising reaction cores into greater specification. The networks then provide an easy mechanism for identifying feasible reaction mechanisms and identifying the most relevant examples for a given set of reactants. Visualisation of reaction conditions such as yield, solvent, temperature, time, presence of acid/base etc. allow for the assessment of the suitability of a suggested purging mechanism. The tool aims to provide a chemisty with support in assessing the purge of an impurity in a specific synthesis stage. This support can encompass: which purging reactions may be seen, support assessment of relevance given conditions and identification of examples.

Supporting the assessment of the purging of potential mutagenic impurities via analysis of known reactions

256th National Meeting (2018)

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