Preparation of dummy molecularly imprinted polymers for selective extraction of aromatic amine genotoxic impurities

作者全名："Fu, Xiaoya; Wang, Xia; Xia, Zhining; Huang, Yike"

作者地址："[Fu, Xiaoya; Xia, Zhining] Chongqing Univ, Sch Pharmaceut Sci, Chongqing 401331, Peoples R China; [Fu, Xiaoya; Huang, Yike] Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China; [Wang, Xia] Chongqing Univ, Sch Med, Chongqing 400030, Peoples R China"

通信作者："Xia, ZN (通讯作者)，Chongqing Univ, Sch Pharmaceut Sci, Chongqing 401331, Peoples R China.; Huang, YK (通讯作者)，Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China."

来源：JOURNAL OF CHROMATOGRAPHY A

ESI学科分类：CHEMISTRY

WOS号：WOS:000904572900004

JCR分区：Q1

影响因子：4.1

年份：2022

卷号：1685

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Molecular imprinting; Dummy template; Genotoxic impurities; 2; 6-dichloroaniline; p-Toluidine

摘要："To ensure drug safety, the quality monitoring of genotoxic impurities (GTIs) which have very trace content in medicine is important. Therefore, it should be established an efficient sample pretreatment method to extract GTIs to achieve specific enrichment. In this work, dummy template molecular imprinting technol-ogy (DMIT) was used as dummy template molecule (DTM) to substitute for the target molecule (TM) for established the pretreatment of the sample containing aromatic amine GTIs. A novel strategy for screen-ing out DTM by calculation of computer simulation is established, where the binding energy between the template and functional monomer has the relatively lowest value (-9.60 kcal/mol). Then dummy template molecular imprinted polymer (DMIP) was prepared by bulk polymerization according to the molar ratio of template molecule-functional monomer-crosslinker = 1:4:8, the prepared DMIP exhibited the highest adsorption ( Q = 8.6 mg/g) and good blotting effect (IF = 1.3) and can simultaneously adsorb three aro-matic amine GTIs. The optimal adsorption conditions were obtained by conditional optimization of solid phase extraction (SPE). The solution of pH 7 was chosen as the loading condition, and methanol/acetic acid (90:10, v/v) was chosen as the elution condition. Finally, we determined 2, 6-dichloroaniline in di-clofenac sodium at a 5 ppm level and p-toluidine as the TMs in torasemide sample at 10 ppm by using DMIT-based solid phase extraction and analysis by HPLC, it satisfied the quality control of GTIs in phar-maceutics. DMIT by this strategy has great potential in the sample preparation of GTIs.(c) 2022 Elsevier B.V. All rights reserved."

基金机构：National Natural Science Foundation of China (NSFC) [21974015]

基金资助正文："Thanks to the support of the National Natural Science Foundation of China (NSFC, No. 21974015) , and the help of Mr. Zheng Guocan and Mr. Zhou Kai from the Analysis and Testing Center of Chongqing University"