title: Stoichiometric molecularly imprinted polymers for the recognition of anti-cancer pro-drug tegafur.
abstract: Molecularly imprinted polymers (MIPs) targeting tegafur, an anti-cancer 5-fluorouracil pro-drug, have been prepared by stoichiometric imprinting using 2,6-bis(acrylamido)pyridine (BAAPy) as the functional monomer. Solution association between tegafur and BAAPy was studied by (1)H NMR titration, which confirmed the formation of 1:1 complexes with an affinity constant of 574±15M(-1) in CDCl3. Evaluation of the synthesised materials by HPLC and equilibrium rebinding experiments revealed high selectivity of the imprinted polymer for the pro-drug vs. 5-fluorouracil and other competing analytes, with maximum imprinting factors of 25.3 and a binding capacity of 45.1μmolg(-1). The synthesised imprinted polymer was employed in solid-phase extraction of the pro-drug using an optimised protocol that included a simple wash with the porogen used in the preparation of the material. Tegafur recoveries of up to 96% were achieved from aqueous samples and 92% from urine samples spiked with the template and three competing analytes. The results demonstrate the potential of the prepared polymers in the pre-concentration of tegafur from biological samples, which could be an invaluable tool in the monitoring of patient compliance and drug uptake and excretion.
authors.affiliation: School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, BT9 5AG Belfast, Northern Ireland, United Kingdom.
authors.forename: Paula
authors.initials: P
authors.lastname: Mattos Dos Santos
authors.affiliation: Medway School of Pharmacy, Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hall
authors.affiliation: School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, BT9 5AG Belfast, Northern Ireland, United Kingdom. Electronic address: p.manesiotis@qub.ac.uk.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Manesiotis
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid; D006801:Humans; D054802:Molecular Imprinting / Q000379:methods*; D052616:Solid Phase Extraction; D005641:Tegafur / Q000032:analysis* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005641:Tegafur
keywords: 5-Fluorouracil; Bioanalysis; Molecularly imprinted polymers; Solid-phase extraction; Tegafur