title: Removal of potentially genotoxic acetamide and arylsulfonate impurities from crude drugs by molecular imprinting.
abstract: The present study describes the synthesis and preliminary testing of molecularly imprinted polymers (MIPs) as scavenger resins for removal of the genotoxic impurities (GTI) acetamide and arylsulfonates from active pharmaceutical ingredients (API). The MIPs were synthesized as monoliths using acetamide or methyl tosylate respectively as templates. The polymers were crushed and subsequently tested in the batch and chromatographic mode for template recognition and potential removal efficiency. Both the acetamide and the tosylate MIPs exhibited a strong memory effect for their templates and selectivity with respect to model APIs. For instance the MIP for acetamide preferentially retained acetamide over other amides, such as formamide, acrylamide, methacrylamide, benzamide and N-tert-butylacrylamide. Moreover, passing model API crude contaminated with the acetamide through the MIPs led to the quantitative removal of acetamide.
authors.affiliation: INFU, Technische Universität Dortmund, 44221 Dortmund, Germany. gszekely@hovione.com
authors.forename: György
authors.initials: G
authors.lastname: Székely
authors.forename: Emelie
authors.initials: E
authors.lastname: Fritz
authors.forename: Joao
authors.initials: J
authors.lastname: Bandarra
authors.forename: William
authors.initials: W
authors.lastname: Heggie
authors.forename: Börje
authors.initials: B
authors.lastname: Sellergren
mesh_terms: D000081:Acetamides / Q000302:isolation & purification*; D001190:Arylsulfonates / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination / Q000517:prevention & control*; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates; D054802:Molecular Imprinting / Q000379:methods*; D009153:Mutagens / Q000302:isolation & purification*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D052616:Solid Phase Extraction / Q000379:methods
chemical_list: D000081:Acetamides; D001190:Arylsulfonates; D008689:Methacrylates; D009153:Mutagens; D004364:Pharmaceutical Preparations; C004919:ethylene dimethacrylate