Synthesis and properties of molecular imprints of darifenacin: The potential of molecular imprinting for bioanalysis

Abstract

A molecularly imprinted polymer has been developed which subsequently demonstrated an ability to selectively retain darifenacin (UK-88,525-S) from aqueous acetonitrile when used as a stationary phase in HPLC columns and as a packing in solid-phase extraction cartridges. The imprinted polymer is applicable to a wide range of analytical methods including extraction from plasma, purification ofradiolabelled UK-88,525, chiral separations and separation of metabolites and structural analogues. The polymer is able to extract darifenacin directly from a protein-precipitated human plasma/ acetonitrile (1:1 v/v) mixture with 100 % recovery. The imprinted polymer can also effect a repurification of 14C-labelled darifenacin. The drawbacks of molecular imprints for ultra-trace bioanalysis (in the sub-nanogram/mL range) are discussed. These centre on the difficulty of removing all the template from the polymer and the consequent effects of template bleed on assay precision and accuracy when used as solid-phase extraction cartridges. Possible solutions to this problem are considered. 0.~. NH2~"'~,, 0 9 ) 9 indicates a chiral centre Figure 1 Structure of darifenacin

Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003

“…345 Template removal is an issue in non-covalent MIPs used for SPE in ultra-trace analysis; in particular slow template bleeding can occur which can interfere with analyte detection. 421,899 A study by Ellwanger et al compared methods for complete template removal to minimize template bleed. 900 The use of analogues or 'dummy templates' 901,902 may help to circumvent these problems.…”

“…416,417 Occasionally combinations of functional monomers have been used to improve the binding properties of MIPs with respect to those formed with a single functional monomer. Combinations that have been used include 2-vinylpyridine with methacrylic acid, 418,419 4-vinylpyridine with methacrylic acid, [420][421][422] acrylamide with methacrylic acid, 423,424 acrylamide with acrylic acid 423,424 and acrylamide with 2-vinylpyridine. [425][426][427] Various custom-designed functional monomers have been reported.…”

Preparation of Uniformly Sized Molecularly Imprinted Polymers for Phenolic Compounds and Their Application to the Assay of Bisphenol A in River Water

“…This problem has been overcome by imprinting a structurally related analogue and combining with chromatographic separations. [5][6][7][8] Previously, MI-SPEs were carried out by an off-line mode. Recently, on-line MI-SPEs have been developed.…”

Ionic Liquids as Porogens in the Synthesis of Molecularly Imprinted Polymers

“…bulk or precipitation. Bulk (or monolith) polymers are prepared using minimal porogen volumes, where the polymer particles coalesce during polymerisation to create a monolithic polymer structure (Venn and Goody 1999). By contrast, precipitation polymers are prepared in a large porogen volume (usually >95% of the polymerisation mixture by volume), allowing the polymer to form in solution as discrete particles.…”