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abstract

A novel potentiometric sensor based on a molecularly imprinted polymer (MIP) for determination of
promethazine (PMZ) was prepared. Promethazine MIP particles were prepared and dispersed in 2nitrophenyloctyl 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±1.0mVdecade−1) over a wide concentration range, from 5.0×10−7 to 1.0×10−1 M, with
a low detection limit of 1.0×10−7Mand a response time of ∼50 s. The method has the requisite accuracy,
sensitivity and precision to assay PMZ in syrup samples and biological fluids.
1. Introduction
Molecularly imprinted polymers (MIPs) are promising materials
for continual use in sensor fields as the recognition element or
modifying agent.AnMIP is a synthetic polymer possessing selective
molecular recognition properties for the shape and positioning of
functional groups because of its recognition sites within the polymermatrix
that are complementary to the analyte molecule. These
materials are similar to biological specific receptors in some ways
because of their high selectivity to the target molecule and their
recognition mechanism [1,2]. MIPs have been used for electrochemical
sensor development as the highly selective recognition
element of the sensor [3–6].
Promethazine is widely used for its antihistaminic, sedative,
antipsychotic, analgesic and anticholinergic properties. However,
promethazine hydrochloride can cause adverse effects in humans,
such as endocrinal, cardiac and reproductive alterations. Therefore,
its determination in commercial formulations and biological
samples is extremely important [7].
Many analytical techniques such as titrimetric procedures
[8–10], spectrophotometric methods [11], spectrofluorometry [12],
high performance liquid chromatography [13] and voltammetry
[14] have been employed for promethazine (PMZ) determination.
Potentiometry is one of the simplest instrumental techniques
that many chemists encounter. Potentiometric sensors provide an exciting and achievable opportunity to perform
biomedical,
environmental and industrial analyses away from a centralized laboratory
because they make it possible to combine the ease of use
and portability of potentiometry with simple, inexpensive fabrication
techniques. While potentiometry has been used for many
years, the advances in the field of ion-selective electrodes make it
a valuable technique in the modern laboratory [15,16].
The unique feature of potentiometry with MIP-based sensors
is that the species do not have to diffuse through the membrane
so there is no size restriction on the template compound. Despite
all these advantages, only a few MIP-based sensors have been
reported that utilize a potentiometric transducer [17–19]. These
studies describe potentiometric sensors created in several different
ways: by dispersing MIP particles in plasticizer and embedding
them in a polyvinyl chloride (PVC) matrix [20–23], by forming a
glassy membrane [24], by assembling the template on the polar
surface of an indium tin oxide (ITO) glass plate [25,26], by depositing
a MIP polymeric film on the gate surface of an ion-sensitive
field-effect transistor [27,28] and by embedding MIPs in the carbon
paste electrode [29].
The potentiometric sensor that has already been reported for
promethazine determination [30,32] usually uses the ion-pairing

2. which suffers from the main disadvantage of low selectivity toward the target molecule. 2. This procedure was repeated four times. It was then kept stirring in an oil bath maintained at 60 ◦C to start the polymerization process. di-n-octylphthalate (DOP). Fabrication of the PMZ sensor The PVC membrane sensors were fabricated by following the general procedure described below. It was found that the MIP composition as determined by the nature of the monomers used for the MIPpreparation had a considerable effect on the final sensor performance. 2.1 g) were added. 2. Deionized water was used throughout. PMZ-imprinted or nonimprinted polymer particles were dispersed in NPOE (DOP or BEHS or DBP) and were added to 2. Preparation of PMZ-imprinted and non-imprinted polymer particles PMZ-imprinted polymer particles were prepared by taking 1mmolof PMZand 7mmolof functional monomer (MAA or VB) in a 50-ml round-bottom flask. 2. the sensor was successively used for promethazine determination in pharmaceutical products and serum samples. The sedimented particles were discarded and those not sedimented were collected by centrifugation. 32mmol of cross-linker (EGDMA or DVB) and AIBN (0. After optimization of the parameters influencing the sensor performance. dibutylphthalate (DBP). ethylene glycol dimethacrylate (EGDMA). Subsequently. Non-imprinted polymer (NIP) particles were prepared analogously without the addition of PMZ during the polymer material preparation. The use of a MIP as the ionophore in the membrane electrode for promethazine determination would be an interesting development in this field because it would provide improved selectivity in the developed sensor. After 12 h.1. Reagents Promethazine hydrochloride and clozapine were obtained from Fluka (Switzerland). Methacrylic acid (MAA). The resulting MIP particles were dried to a constant weight under vacuum at 60 ◦C and were used in the following experiments. Then.agent as the ionophore. The particles collected were suspended in acetone again and allowed to settle for 4 h. All other chemicals were of analytical reagent grade and were obtained from Merck (Germany). The resulting solution was homogenized in a sonicator and then poured into a Teflon mold. creating the first MIP-based promethazine sensor. followed by centrifugation. In this work. 2nitrophenyl octyl ether (NPOE). bis(2ethylhexyl) sebacate (BEHS) and high-molecular-mass poly(vinyl chloride) (PVC) were purchased from Aldrich (USA). The PMZ and unpolymerized monomers were removed by Soxhlet extraction with 100 ml of methanol by refluxing for 12 h. the obtained polymer materials were ground and sieved.5 ml of tetrahydroforan (THF)containing PVC. divinylbenzene (DVB). 4-vinylpyridine (VB). Experimental 2.2-azobisisobutyronitrile (AIBN). The mixture was then left in contact for 5min for prearrangement. a molecularly imprinted polymer with recognition sites for promethazine was prepared and then used to fabricate the promethazine-selective potentiometric sensor. the particles were suspended in acetone and allowed to settle for 4 h. Drug-free human serum was obtained from the Iranian blood transfusion service (Ardabil.3. The mixture was purged withN2 for 10 min and the flask was sealed under this atmosphere. The THF was allowed . Iran) and stored at −20 ◦C until use after gentle thawing.

5mm.5 for 3 h.5) was measured. the extraction was repeated on the residual aqueous layer. Primary evaluation of MIP and NIP particles prepared with different composition Three different monomer compositions were used for preparation of MIP and NIP particles under identical synthesis conditions and at the same mole ratios of cross-linker/functional monomer/template. The calibration curve for serum samples was also prepared using buffer solution. The sensor was kept in air when not in use. The tube was then filled with an internal filling solution of 10−3M of PMZ. After drying. Fig. The membranes were glued to one end of a glass tube. and then the solution was diluted to the mark with urine and vortexed for 1min. The EMF was plotted as a function of PMZ concentration. For this procedure.1. Hg. It can be seen that in all three polymers there is no differences between the MIP and NIP with the same structure with regards to the size and surface morphology of the polymeric particles.4. The quantity of promethazine–HCl per ml of syrup was calculated from the standard calibration graph and required calculations. The mixture was centrifuged at 1000rpm for 3min to separate the aqueous and organic layers. Results and discussion 3. a simple batch extraction procedure coupled with a colorimetric detection method [33] was applied. 2. the samples were reconstituted with 15 ml of buffer. 2.1Mbuffer (pH 2. 1ml of PMZ aqueous solution was transferred to a 5 ml volumetric flask. Then. the solution was adjusted to a pH of 10 by the addition of a concentrated sodium hydroxide solution. the above procedure was followed and the membrane potentials were measured. The response of the sensor was examined by measuring the electromotive force (EMF) of the following electrochemical cell: Ag.1Mbuffer with a pH of 2. 1 shows the scanning electron microscopy (SEM) images of the MIPs and NIPs having structures of MAA-EGDMA. Then. After removal of the organic layer. 2ml dichloromethane was added to 1ml of serum samples and vortexed for 2min. 2.6. An aliquot containing 1×10−6 to 1×10−2M was taken. Syrup sample preparation and determination Syrup containing 5mg/ml of promethazine–HCl was diluted with distilled water.5. In this study. The dichloromethane layers were pooled and dried at 40 ◦C under a gentle stream of nitrogen. The PMZ adsorption capabilities of MIPs and NIPs created from the three polymeric structures were also investigated. the analysis was conducted. For the determination of PMZ. AgCl. The measurements were conducted from low to high concentration of PMZ. Analytical procedure The sensor was conditioned in 25 ml of 0. 1. In addition. The polymer membranes thus obtained had a thickness of ∼0. 3. 5×10−5M . VB-EGDMA and VB-DVB. The potential response of the sample solution containing varying amounts ofPMZin 50ml of 0. it is clear that the MIPs and NIPs with the VB-DVB structure have a larger size and a different morphology in comparison to the other synthesized polymers.0×10−3M PMZ|PVC membrane|sample solution||KCl (saturated)|Hg2Cl2. Preparation of serum samples and extraction procedure For the preparation of serum standard solutions.to evaporate at room temperature. as indicated in the general analytical procedure.

518 and 11.of PMZ solution was prepared and 0. The binding energy (_E) of PMZ with MAA and VB was calculated in order to theoretically evaluate the interaction between the PMZ and the polymers prepared by monomers of MAA and VB. In addition. 70:30. It can be seen that both the MIP and NIP prepared with MAA and EGDMA adsorb the PMZ more than the two other polymers. The higher the template–monomer binding energy. However.05 g ofMIP or NIP powder was contacted with PMZ solution for 30 min with stirring. It is evident that in all polymeric structures. For the same conditions. the more intensive the template interaction with the polymer backbone and also with polymer-selective sites containing that monomer. Regarding the similarity between the MIP and the NIP according to the SEM images. respectively (shown in the inset of Fig. it can be concluded that the presence of recognition cavities in the MIP is the main reason for the higher adsorption capability of the MIP over the NIP in all polymeric structures. Then. Because the washing mainly removed the PMZ molecules adsorbed on the polymer surface (socalled surface adsorption). The calculated energies for the PMZ-MAA and PMZ-VB interactions were equal to 176. removed 11% of the adsorbed PMZ from the MIP prepared with VB and DVB. From these results. It must be mentioned that the amount of PMZ adsorbed by recognition cavities on the MIP in the case of the MAA-EGDMA-based polymer was also high because. it can be concluded that a considerable portion of the PMZ uptaken by the MAA-EGDMA polymer occurs because of a weak surface adsorption mechanism. For the VB-DVB MIP. The binding energy of PMZ with the monomer was obtained from the following equation: _E = E(PMZ-monomer) − E(monomer) − E(PMZ). although the total adsorbed amount of PMZ was low. The _E of the interactions of the template with these monomers was calculated by the density functional theory method at the B3LYP/6-31G level (Gaussian 98 software) after preliminary energy minimization by molecular mechanics. washing of the MIP and the NIP with a proper washing solution (water/ethanol. the adsorption capability of the MIP is better than that of the NIP. This conclusion was made by comparison of the amount of PMZ present before and after the washing step. Because the mentioned functional groups exist on both the surfaces and the selective cavities of the . it was found that most of the PMZ adsorbed on the NIP was removed by washing for all the polymeric structures. PMZ was chosen as the template molecule and MAA and VB were chosen as the functional monomers.549 kJ/mol. even after the washing step. respectively. The results obtained are illustrated in Fig. The optimized conformations of PMZ and the mentioned monomers are shown in Fig. the washing could remove 46% and 55% of the PMZ adsorbed on the MIP made of VB-EGDMA and MAA-EGDMA. the MIP or NIP was separated from the solution and the non-adsorbed PMZ was measured in the solution by the colorimetric method. it can be concluded that PMZ can interact more strongly with the MAA-based polymer as compared to the VB-based polymer. 2. For the computational approach. 3. The calculation was carried out in the gas-phase state. most of the PMZ uptaken was fixed at recognition cavities. 2). The high surface adsorption capability of MAA-EGDMA-based MIPs and NIPs can be attributed to the smaller size of these polymers and the presence of carboxylic acid functional groups in the polymer structure that seem to be able to interact strongly with promethazine molecules. v/v). the PMZ remaining on the MAA-EGDMA MIP was still larger than for other types of MIPs at the same conditions.

for VB-DVB.resulting polymers. In the mentioned voltammetric sensor. PMZ is not required to diffuse through a membrane and the PMZ ions adsorbed on the surface (by simple surface adsorption and by the recognition sites on the MIP surface or those in the proximity of the surface) are responsible for the membrane potential creation. Because of the nonselective nature of the surface adsorption. Thus. For this reason. both the MIP and the NIP adsorbed PMZ intensively. indicating the strong recognition capability of the MIP. As can be seen. in the case of MAA-EGDMA. However. In the potentiometric sensor. in the case of the VB-DVB MIP.and NIP-based membranes in response to PMZ. whereas the NIP-based sensor’s response to the PMZ is not noticeably regular for most tested values of PMZ concentration.and NIP-based electrode to PMZ are identical for all the tested PMZ concentrations. 4. As a general conclusion from this study. Here. in the polymer with the MAA-EGDMA composition. which generally has a non-selective nature. there is a similarity in the responses of the MIP. it can be said that the response of the MIP electrode originates from two sources: selective site interactions (presented as cavities on the surface of the MIP particles) and the surface adsorption effect. Although the washing removed most of the PMZ from the MIP with the MAA-EGDMA structure. This led to noticeable differences between the MIP.and NIP-based electrodes to PMZ. Because the NIP contains no predesigned selective cavities for PMZ and the only way for the NIP to uptake PMZ is through surface adsorption. if the surface adsorption capability of the MIP for a target molecule is high. the MIP-based sensor responds to the PMZ in a near-Nernstian manner. the use of a simple washing step before the electrochemical determination and after the extraction step could remove the weakly adsorbed analyte (surface adsorption) from the MIP. the membrane potential response to the analyte will be intensively affected by the surface adsorption. and most of the PMZ adsorbed to the MIP was present because of the selective recognition of PMZ by recognition sites on the MIP. there is a noticeable difference between the MIP. it was not possible to differentiate the surface-adsorbed PMZ from PMZ recognized by the selective recognition sites present on the surface or in the proximity of the MIP surface. the response of the electrode under such conditions is not selective enough toward PMZ. However. the surface adsorption was not large. the responses of the MIP. unlike other electrochemical methods such as voltammetry [3. However. It is also clear that in the case of VB-EGDMA. the PMZ remaining on the MIP after washing was still high. in this case. the large similarity in the responses of MIP.and NIP-based membranes in response to PMZ. it can be concluded that the polymer based on the MAA monomer uptakes PMZ more intensively than the polymer with the VB structure.2. As was described above. It was also proved that most of this adsorption occurred because of surface adsorption.and . This theoretical finding is in agreement with the previously explained adsorption results and the following potentiometric results. Effect of polymer structure on the potential responses of membrane sensors The plots of the potential responses versus the decade of PMZ concentrations for the three described MIP. 3. and the selective sites of the MIP will not properly show their recognition capabilities. However.4]. in the potentiometric method. partial distinction of the MIP in comparison to the NIP is possible.and corresponding NIPbased membranes are comparatively illustrated in Fig. it can be seen that the MAA-EGDMA NIP responded to the PMZ concentration change like a MIP.

the NPOE-basedmembrane showed a lower detection limit and a wider linear range.These solvent mediators strongly influence the working concentration range of potentiometer sensors [36].24. In addition. The effect of different plasticizers—NPOE. the difference between the MIP-based membrane and the NIP-containing membrane was very noticeable when NPOE was applied as a plasticizer. the considerable observed difference between the MIP. DBP and DOP—on the performance of the PMZ sensor was investigated. It was found that using BEHS.35] and imprinted. Hence. The appropriate characteristics of the membrane containing NPOE can be directly related to the higher .NIP-based MAA-EGDMAmembranes can be attributed to the dominance of the surface adsorption over the selective site interactions.and NIP-based membranes was not as large.7) and 53. These slopes were larger than that of the membrane prepared withNPOE(31.0)). slope and response time in the cases of conventional ionophore-based sensors [34. It must be mentioned that in order to select the best ratio. polymer-based. 3. BEHS. respectively. different aspects of the membrane preparation using PMZ-imprinted polymer particles were optimized along similar lines. DBP and DOP as plasticizers resulted in calibration curve slopes of 47. The following selectivity study was conducted to prove this statement. 50.and NIP-based sensors is necessary.4. chosen as a similar compound to promethazine. Overall. It can be seen that the MAA-EGDMA-based sensor could not differentiate these two molecules. Thus.and NIP-based sensors and the results obtained are shown in Table 1. Response of MIP particles (VB-DVB) to PVC ratio It has been proved that the ratio of ionophore to PVC influences the working concentration range. However.8 (±1.2). in comparison to NPOE. we selected this structure for further investigation. Effect of membrane composition There are a great number of reports on conventional potentiometric sensors that show that the response behavior of the sensor depends on various features of membranes such as the properties of the plasticizer and the nature and amount of ion recognizing material used [23. 5 shows the potential response behaviors of three membrane electrodes prepared by using different MIP structures for chloropromethazine.2 (±1. the PMZ sensor gave a narrower linear response range and poor detection limits with plasticizers like BEHS. Both criteria can be seen in the MIP to PVC ratio of 1:2. Taking into account the demonstrated results and considering the differences between the potentiometric sensors prepared with MIPs and NIPs of VB-DVB polymer. As mentioned before. From the presented results. a study was conducted with MIP.3 (±3. DBP and DOP. ion-selective electrodes [23. Weobserved that the ratio ofPVCto imprinted polymer particles played a key role in the efficiency of the sensors because the amount of imprinted polymer particles determines the number of binding sites available for recognition. 3. this can be attributed to the low surface adsorption in the case of VB-DVB-based MIPs. it is clear that the membrane with aMIP particle toPVCratio of 1:2 gave the best response. in addition to the proper response of the MIP-based sensor.37].36].3). Fig. For the other mentioned plasticizers. the response difference between the MIP. The addition of an appropriate plasticizer leads to the proper physical properties and ensures high mobility of thePMZions in the membrane.3.5 (±2. whereas the electrode prepared with VB-DVB demonstrated considerable selectivity to PMZ over chloropromethazine for most of the tested concentrations.

Afterwards. were checked.2 ml of NPOE in the membrane led to better physical properties and resulted in optimum analytical characteristics such as a wider linear range. a study was conducted to find the proper amount of NPOE.0–5. Response time and memory effect evaluation In Fig.0×10−4M (by appropriate dilution of the solution. In addition. the non-imprinted membrane did not respond to PMZ below 1×10−4M and gave a linear response for PMZ . As can be seen. as obtained from the above studies.0×10−3Mat the next step (the second raising portion of the curve). the concentration was reduced from 1.0–6. 7) demonstrated a linear response in the range from 5×10−7 to 1×10−1 M. Therefore.0. no unwanted memory or hysteric effect was found for the sensor. Sensitivity and detection limit The potential responses of PMZ-imprinted and control polymer membrane sensors fabricated under optimal conditions. 8.7. the first raising portion of the curve). the measurements performed in the sequence of high-to-low concentration indicate that the response of the MIP-based electrodes was reversible. the resulting potential–time responses of the membrane electrode prepared with VB-DVB are presented. However. Effect of test solution pH The effect of the pH of the solution on the performance of the PMZ sensor was studied by varying the pH in the range of 1.0×10−3 to 1.0×10−6 to 1. the potentials remained constant in the range of 2. The potential–time response behaviors were obtained upon changing the promethazine concentration from 1. it is evident that in spite of the required longer time (120–145 s) needed to return the potential to its initial value in the dilution step. 3.0×10−4 to 1.5.0×10−4M (by fast injection of _l amounts of a concentrated solution.5.2 mV. Afterwards. in order to check thememoryor hysteric effect of the sensor. a pH of 2. Thus. 31. was chosen for further promethazine determination by the proposed sensor. a lower detection limit and a Nernstian slope. although the time needed to reach the equilibrium value for the case of high-to-low sample concentration was longer than that of the lowtohigh sample concentration because of the filling of the cavity in the imprinted polymer with the target molecule. The calibration plot obtained from MIPs and NIPs of VB-DVB polymer (based on triplicate measurements at each concentration) is shown in Fig.6. NPOE was selected as the plasticizer. 7. 3. On the other hand. fixed with monochloroacetic acid–based buffer.0×10−6M at the next step (the second descending portion of the curve). This was followed by changing the PMZ concentration from 1. The observed potential drift at lower pH values may be attributed to the membrane response to H+ and at higher pH values (pH > 5) could be due to the change of the promethazine ionic charge. The results are illustrated in Fig. indicates that the sensor obeys the Nernstian law and also proves that the [PMZ]2+ species of promethazine are mainly responsible for creating the potential responses. The limit of detection was calculated to be 1×10−7M based on the IUPAC definition. It is evident that the potentiometric response of the electrode prepared with MIP particles was rapid (50 s) and reversible. It was also found that PMZ membranes were brittle in the absence of plasticizer and could not be used for recording sensor performance. 3. the first descending portion of the curve).dielectric constant of the NPOE plasticizer [23]. The concentration was further reduced from 1. It was found that using 0. 6. The slope of the obtained calibration curve.0×10−4 to 1. The linear working concentration plot (shown in the inset of Fig.0.

is then given by the resulting primary ion activity (concentration) to the interfering ion activity ratio: KMPM PMZ. Analytical application 3.3% (n = 5). According to the MPM method. 3. When the MIP sensor is used to measure promethazine. in addition to sensitivity and selectivity. The coefficients describe the preference of the developed membrane electrode for an interfering ion. For membranes constructed with NIP. The better response characteristics of the PMZ-imprinted sensor over the non-imprinted polymer-based sensor over the entire concentration range are attributed to a significant imprinting effect. The reproducibility of the sensor was evaluated with five repeated potentiometric measurements of the 1.0×10−5M promethazine solution. The mean percentage recovery.in the concentration range from 1×10−3 to 1×10−1 M.X = apmz aX . the selectivity coefficients were small enough to cause interference in the promethazine determination.9. Stability and reusability Two important criteria required for any sensing device.11. X.5 are listed in Table 2. The MPM selectivity sequence of the employed MIP for different drugs and organic materials approximately obeys the following order: chloropromethazine > methylene blue > clozapine > hydroxyzine >metchachlorpramide > pyrrole > aniline. Analysis of promethazine in syrup sample The proposed potentiometric procedure was successfully applied for promethazine determination in syrup samples. obtained by applying the calibration curve method.0×10−6M promethazine). This again proves the presence and proper functioning of selective cavities in the MIP. all the other substances (except for chloropromethazine) hardly interfere with the determination.X. The . KMPM PMZ. the interfering ions (X) are successively added to an identical reference solution until the measured potential matches that obtained before the addition of the primary ions.3%. and the potential is measured. the obtained selectivities for the tested compounds were noticeably lower than those of the MIP-based membrane electrode. with reference to the promethazine ion. Interference study The potentiometric selectivity coefficients were measured by the matched potential method (MPM) [38]. are stability and reusability. 3. In most cases. was 103. The MPM selectivity coefficients for the promethazine ionselective electrode prepared with MIP and its corresponding NIP at the constant pH value of 2. The MPM selectivity coefficient.11. The precision of the described procedure in terms of relative standard deviation was 5. The above-developed PMZ sensor was found to be stable (deviation less than 1mV for 1×10−4Mof PMZ) for 2months and could be reused more than 10 times without any loss in sensing ability. the specified activity (concentration) of the primary ions is added to a reference solution (1.10.1. 3. 3.8. Accuracy and reproducibility The accuracy of the described potentiometric measurements was checked by calculating the recovery of a known promethazine concentration (1×10−5 M). In another experiment.

resulting data obtained from the calibration curve procedure were statistically compared with the labeled amounts on the syrup and those obtained by the spectrophotometric method [33]. This method is based on the oxidation of promethazine by potassium persulfate and measurement of the absorbance of the resulting colored product at a wavelength of 510nm (_ max).2. Its accuracy. Promethazine assay in spiked human serum The proposed potentiometric procedure was also successfully applied to an assay of promethazine in spiked human serum. we investigated the effect of MIP composition on the potentiometric sensor performance. rapid and simple promethazine detection in pharmaceutical formulations and human blood. The recoveries of the methods were in the range of 96–110% for the spiked serum. Consequently. The described sensor introduces a new strategy for constructing potentiometric chemosensors for specific. In this work. It was shown that proper attention to the polymer structure and the surface adsorption on MIPs can be effective in appropriately designing and preparing potentiometric sensors that utilize MIPs. reproducibility. 4. The potentiometric MIP sensor prepared with VB-DVB showed a considerable difference in response to promethazine in comparison to the corresponding NIP-based sensor.11. The results are presented in Table 3. satisfactory results were obtained from the proposed sensor. It was shown that the presence of selective cavities in the MIP structure was not enough of a criterion for proper functioning of the resulting sensor. Conclusion The potentiometric sensor employing a MIP as the ionophore in a PVC membrane electrode provided an attractive alternative for the measurement of promethazine. 3. The results of the recovery studies are listed in Table 4. As can be seen. simplicity and selectivity suggest its application would be appropriate in quality control analysis and clinical laboratories . it was concluded that the suggested method was sensitive and precise.