Design, preparation and characterization of novel molecularly imprinted polymers for removal of potentially genotoxic 1,3-diisopropylurea from API solutions

György Székely, Joao Bandarra, William Heggie, Frederico Castelo Ferreira*, Börje Sellergren

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

This paper describes the design and synthesis of novel molecularly imprinted polymers (MIPs) for the selective removal of a potentially genotoxic impurity (GTI) from active pharmaceutical ingredient (API) post reaction streams. Due to safety concerns, concentration levels of GTIs allowed in pharmaceutical products have been driven down to stringent low values. Therefore, novel MIPs have been prepared with the aim to address this challenge. The model molecules selected for this study were 1,3-diisopropylurea (IPU), as a potential GTI and keppra (KP), mometasone furoate (Meta) and roxithromycin (Roxi), as APIs. The MIPs were prepared using IPU as template and methacrylic acid (MAA), in the free acid or anionic form, as functional monomer. Typically, in industrial post reaction streams, API concentrations are significantly higher than those of IPU. Therefore, the novel MIPs were tested under such a scenario. To test the effect of different host-guest interactions, MIP1 and MIP2 were prepared in the absence and presence of a base, respectively. A highest degree of IPU binding, at a value of 80%, was obtained for MIP2, with only 15% non-specific binding of APIs, regardless of API size and chemical structure. The enhanced performance of MIP2 is in agreement with the incorporation of a carboxylate anion in the MIP, which interacts more strongly with IPU than the neutral free acid.

Original languageEnglish (US)
Pages (from-to)190-198
Number of pages9
JournalSeparation and Purification Technology
Volume86
DOIs
StatePublished - Feb 15 2012
Externally publishedYes

Keywords

  • 1,3-Diisopropylurea
  • API purification
  • Genotoxic impurities
  • Host-guest system
  • Molecular imprinting
  • Pharmaceuticals

ASJC Scopus subject areas

  • Analytical Chemistry
  • Filtration and Separation

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