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

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.