Development of a semiautomated procedure for the synthesis and evaluation of molecularly imprinted polymers applied to the search for functional monomers for phenytoin and nifedipine

A previously described scaled-down version of the established monolith proc edure, where molecularly imprinted polymers (MIPs) are prepared on the bott om surface of chromatographic vials [Anal. Chem. 71 (1999) 2092] has been h ere further optimised with respect to its full automation. The protocol res ults in savings of time and reagents compared to the monolith procedure, al lowing ca. 60 polymers (similar to 50 mg each) to be synthesised in paralle l. Both blank and imprinted polymers are then evaluated in situ by equilibr ium batch rebinding tests, Each step in the synthesis and evaluation was co nsidered with the aim of achieving an automated method with wide applicabil ity with regards to template targets and monomer compositions. A system bas ed on thermal initiation was considered easier to implement and applicable to a larger number of templates than one based on photo-initiation. For the purpose of choosing a suitable initiator, azo-initiators with different di ssociation energies were compared, 2,2'-Azobis(2,4-dimethylvaleronitrile) ( V-65) was selected as the initiator of choice based on the observed rebindi ng selectivity and the low temperature of use (45 degreesC). The time of de gassing and polymerisation were also considered, With respect to the reprod ucibility of the automated procedure, confidence values of the mean rebindi ng percentage of 12 and 8 were found, respectively, for the blank and impri nted polymers when five parallel batches of ametryn blanks and imprints wer e submitted to rebinding tests. The small-scale protocol was then applied t o the search for functional monomers for two further templates of interest: phenytoin and nifedipine. The results of the rebinding experiments on the small scale were found to be in agreement with the equilibrium rebinding ev aluation of the regular scale batches. However, the equilibrium rebinding r esults cannot be used as a general predictor for the chromatographic select ivity of the MIPs. (C) 2001 Elsevier Science B.V.. All rights reserved.