DEVELOPMENT AND VALIDATION OF THE EVALUATION OF RELATED IMPURITIES IN SOME DRUG ENTITIES BY LC MS METHODS AND THEIR EFFECTS BY SCREENING ON BACTERIAL DNA

Abstract

This studty deals with the development and validation of analytical methods for the estimation of IM s in selected drug candidates. LC-MS method is used for the estimation of IM s in the selected drug candidates, estimation in the commercially available pharmaceutical formulations and validation of the developed methods with the their genotoxicity evaluations. newlineThe results of the experiments carried out to check the accuracy, reproducibility of the methods were presented and discussed. System suitability studies and GT evaluations were also arried out. newlineThe following are some of the salient features and conclusions made for the present study: newline The BZL, BZA and 5BNA IM were the reactant impurity present in the PHY, WAR and 5BNA. newline The RI present in the API and dosage forms were monitored as per ICH guidelines Q3B(R2). newline These IM s were estimated by LCMS analysis. newline The developed methods were simple accurate, precise and sensitive to estimate the BZL, BAZ and 5BNA present in PHY, WAR and NIC respectively . newline They can be useful to quantify the RI present in API and dosage forms. newline BZL present in the Phenytoin drug was not within the limit in one tablet dosage form. But the quantity of BZA in WAR was within the limit. newline The carcinogenicity of BZL and BAZ were screened by AMES Test. It was proved that the Qualification limit showed the carcinogenicity effect due to the keto group present in BZL60. newline It was proved that the acceptable limit of concentration of BAZ has shown the carcinogenicity effect due to the keto group present in BAZ. newline The 5BNA present in the NIC drug was not within the limit. newline The carcinogenicity of the 5-BNA was screened by NICKING assay and it was proved that qualification limit has not shown the carcinogenicity effect. newlineIn case of IM s the bio-safety of the IM s does not depend of quantitative level. The IM s present with in limit, the chronic exposure of IM s in terms of time and different concentrations are to be evaluated during the drug development stage.