Quality Research And Stability Researc Of Clofazimine

Clofazimine was launched for the treatment of leprosy by Ciba Geigy in 1969,under the brand name Lamprene,and was approved by FDA in 1986.In current stage,clofazimine mainly become an adoption of treatment on infections,especially on the infections in which the bacterial strain has resistance to sulfone drugs.Leprosy is not popular in the worldwide,but it is our long-term aim to eliminate it.From this point,it is meaningful to produce clofazimine drugs with proper price and high quality.In this test,there are systematic analyses on relative substance and genotoxic impurities about Clofazimine produced by Zhejiang Huahai Pharmaceutical Co,ltd,which ensure the high quality.For the control of related substances,the tightened specification and effective HPLC methods are established after consulting the specification and analytical methods recorded in China pharmacopoeia,European pharmacopoeia and the U.S.pharmacopoeia and combining with the Huahai's synthetic process route.This HPLC method is validated scientifically,and the results show that the method is specific,accurate,precise and robust.The linear range of impurity A was 0.125-0.375?g/mL,precision RSD was 2.8%and accuracy recovery was 101.9%-105.3%.The linear range of impurity B was 0.113-1.125?g/mL,precision RSD was 2.0%,and accuracy recovery was 99.8%-100.3%.The linear range of clofazimine ketone was 0.125-0.375?g/mL,precision RSD was 2.0%,and accuracy recovery was 106.2%-106.7%.For the control of genotoxic impurities,four impurities are considered as genotoxic impurities or potential genotoxic impurities according to analysis of synthetic process route of Clofazimine,consulting guidelines on genotoxicity in ICH,the literature data and analysis results of the drug structure toxicity prediction software(ACD/Percepta 14.2.0 Build 2977).An appropriate control method is developed,and the research results show that the method is specific,accurate and sensitive.The accuracy result of 1-fluoro-2-nitro-Benzene was 104.3%.The accuracy result of 1-amino-4-chlorobenzene was 112.8%.The accuracy result of 2-Nitro-4'-chlorodiphenylamine was 103.4%.The accuracy result of 2-Amino-4'-chlorodiphenylamine was 102.5%.Accelerated and long-term stability study provides scientific evidence for manufacturing,packaging,storage and transportation of Clofazimine.Meanwhile,the 24 months retest date of Clofazimine is preliminarily determined based on the results of stability study.In addition,during development and research process of related substance analytical method,the generation mechanism of ghost peak was identified.The elimination of ghost peak was found as per this mechanism.This study could provide valuable reference for other analysts.