Research For Potential Genotoxic Impurity In Raw Materials Of Indapamide

Genotoxic impurity can damage DNA cells directly or indirectly, generate gene mutations or mutagenesis in vivo, with cancer-causing potential or tendency. National regulatory authorities such as ICH, FDA, EMAetc. have the specific requirement about genotoxic impurity, more and more pharmaceutical producing enterprise focus on control and testing of genotoxic impurity in the process of new drug research and development.Indapamide as common medication for anti-hypertension, it is very important for comprehensive study on potential genotoxic impurity in Indapamide API. The maximum daily dose(MDD) of Indapamide is 10mg/day. Thus, the acceptable limit of genotoxic impurity in Indapamide API is not more than 150 ppm, which is calculated by TTC(1.5 μg/day).This thesis base on research the raw materials used in the process of Indapamide manufactured by Suzhou Lixin Pharmaceutical Co., Ltd. Determine the potential genotoxic impurity in raw materials of Indapamide. Establish the acceptable limit of these genotoxic impurities according to domestic and internationalregulatory requirements, anddevelop appropriateanalytical method to test these residual quantities in Indapamide. Assess the results whether within the limits of regulatory requirements.This article analyzes three potential genotoxic impurities:thionyl chloride, Chlorosulfuric acid and Benzene. According to characteristics of each impurity and process characteristics, carry out the compliantmethodology validation of established method for test the residual impurities with appropriateinstrument and determination condition etc.