Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol

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作   者：

Rossi S.;  Bussi S.;  Bonafe R.;  Incardona C.;  Vurro E.;  Visigalli M.;  Buonsanti F.;  Fretta R.; 

作者机构：

Bracco Imaging SpA Global Medical & Regulatory Affairs Medical Writing;  Bracco Imaging SpA Bracco Research Centre; 

关键词：

Impurity;  Ames;  In vitro mutagenicity;  In silico mutagenicity;  Derek Nexus; 

期刊名称：

Mutation Research - Genetic Toxicology and Environmental Mutagenesis

i s s n：

1383-5718

年卷期：

2024 年 893 卷

页   码：

503720-503720

页   码：

摘   要：

? 2023 The Authors5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus? and Leadscope?. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7). However, contrary to the in silico prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.