Molecularly imprinted solid phase extraction micro-column with differential pulsed elution for theophylline determination

The technique of molecular imprinting is used to produce an extensively cross-linked poly(methacrylic acid-co-ethylene dimethacrylate) material that contains theophylline as a print molecule. After Soxhlet extraction of the theophylline, binding sites are formed in the polymer with complementary size, shape, and positioning of chemical functionalities for high theophylline selectivity. The molecularly imprinted polymer has good binding capacity, chemical stability, and physical robustness properties which make it an ideal packing material for micro-columns used in solid phase extraction. Pulsed elution of the bound theophylline can be accomplished through injection of 20 mu l of methanol, which has the proper polarity and protic nature to disrupt the hydrogen bonding and electrostatic interactions between basic theophylline molecules and acidic binding sites. Nonspecific adsorption of interfering drugs can be eliminated by a novel differential pulsed elution, without sacrificing the selective binding of theophylline. This novel microanalysis technique, MISPE-DPE, offers the advantage of micro-scale performance for sample introduction, chemical interference removal, and spectrometric theophylline determination over a linear dynamic range of 1-100 mu g/ml. (C) 1999 Academic Press.