In vitro genotoxicity of piperacillin impurity-A

Abstract

The manufacturing and storage of the piperacillin produce different impurities of various concentrations, which may influence the efficacy and safety of the drug. Since no report of genotoxicity data is available on the impurities of piperacillin, further studies were designed and conducted to provide information for establishing the safety profile and qualification of the piperacillin impurity-A. Salmonella typhimurium strains were exposed to Piperacillin impurity-A for Ames tests. Neither increase in number of revertants indicative of mutagenic activity nor inhibition of bacterial growth, indicative of cytotoxicity were observed up to 5 mg/plate both in the presence and absence of metabolic activation. Similarly, chromosomal aberration assay did not reveal any significant alterations up to 5 mg/culture as compared to the negative control both in the presence and absence of metabolic activation (S9 mix). The results of these studies indicate that Piperacillin impurity-A is non-mutagenic in Ames test and non-clastogenic in chromosomal aberration study.