Title:
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The application of molecular imprinted polymers to the solid phase extraction of drugs
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Molecular imprinted polymers (MIPs), prepared to propranolol, were evaluated as solid
phase extraction (SPE) phases. Monolithic MIPs were converted to particulate SPE
materials by crushing, sieving, and sedimentation to remove fines. A high proportion
(85%) of template propranolol was recovered with initial washes of the MIPs. Template
leaching diminished with successive washes though low level leachings till compromised
analysis of propranolol at trace levels (<5ng/mL).
It was possible to retain propranolol on the MIPs following application in aqueous
solution, biological matrices and organic solvent. In reversed and normal phase mode it
was necessary to include an acid or base to achieve elution of basic compounds. In
reversed phase mode, propranolol-imprinted MPs showed a degree of selectivity when
using methanol:water:triethylamine but not methanol:water:trifluoroacetic acid elution
solvents. This selectivity was related to structure when structurally-diverse compounds
were assessed. Selectivity was very limited when assessed using compounds structurally similar
to propranolol. In normal phase mode, MIPs retained amino-alcohols more strongly
than a non-imprinted polymer though there was no evidence of a structure-related
selectivity. A non-imprinted polymer and one prepared to an alternative template
(tamoxifen) were assessed as reference polymers by which to assess the selectivity of
propranolol-imprinted MIPs. Both materials were suitable references in reversed-phase
mode though little selectivity was evident. The non-imprinted polymer was a poor
comparator in normal phase mode as it appeared to show lesser non-specific binding than
the imprinted MIP.
Reversed and normal phase SPE methods were successfully developed for compounds
structurally-simila to propranolol from human plasma. A protein precipitation step ahead
of SPE was necessary. The MEP-based asays showed no advantage over conventional SPE
and solvent extraction assay approaches. Although MIP-based extracts were clean,
accuracy was poor at low concentrations (2 and 5 ng/mL) due to interference from template
impurities leaching from the MJP.
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