Molecularly imprinted polymer strategies for removal of a genotoxic impurity, 4-dimethylaminopyridine, from an active pharmaceutical ingredient post-reaction stream

Molecularly imprinted polymers (MIPs) are prepared and evaluated for the effective removal of the genotoxic impurity (GTI), 4-dimethylaminopiridine (DMAP), from a Mometasone furoate (Meta) solution, used as a case study relevant for the pharmaceutical industry. The MIPs formation by bulk polymerization is assessed considering different temperature regimes as well as stoichiometry of template, functional monomer, cross-linker, respectively DMAP, methacrylic acid and ethylene glycol dimethacrylate. A design of experiment (DoE) is performed to establish conditions for a maximum GTI specific binding percentage, validated experimentally at a value of 98% for 5,03 mgGTI/gMIP, for a 256 ppm GTI solution. The MIP robustness and recyclability are successfully evaluated over 6 cycles. Multistep approaches, using MIP alone or in combination with organic solvent nanofiltration (OSN), are discussed aiming to minimize API losses with removal of GTI to reach the threshold of toxicological concern (TTC) for two case studies. (C) 2016 Elsevier B.V. All rights reserved.