A novel potentiometric sensor based on a molecularly imprinted polymer (MIP) for determination of promethazine (PMZ) was prepared. Prornethazine MIP particles were prepared and dispersed in 2-nitrophenyloctyl ether and then embedded in a polyvinyl chloride matrix. The effect of the monomers type on the sensor performance was investigated, and an important role for this parameter was shown. It was shown that the membrane electrode with a MIP prepared by vinylbenzene and divinylbenzene had a better performance in comparison to membrane electrodes containing MIPs prepared with methacrylic acid-ethylene glycol dimethacrylate or vinylbenzene-ethylene glycol dimethacrylate. After optimization, the membrane electrode constructed with a MIP of vinylbenzene-divinylbenzene exhibited a Nernstian response (31.2 +/- 1.0 mV decade(-1)) over a wide concentration range, from 5.0 x 10(-7) to 1.0 x 10(-1) M, with a low detection limit of 1.0 x 10(-7) M and a response time of similar to 50 s. The method has the requisite accuracy, sensitivity and precision to assay PMZ in syrup samples and biological fluids. (C) 2010 Elsevier Ltd. All rights reserved.