J. Iran. Chem. Soc., Vol. 7, No. 3, September 2010, pp. 759-769.

JOURNAL OF THE
Iranian
Chemical Society

Molecularly Imprinted Polymer Based PVC-Membrane-Coated Graphite Electrode for

the Determination of Metoprolol
M. Saber Tehrani*, M.T. Vardini, P. Abroomand Azar and S.W. Husain

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Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran

(Received 2 October 2009, Accepted 9 November 2009)

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A PVC-based membrane containing metoprolol molecularly imprinted polymer (MIP) coated directly on graphite electrode for
the determination of metoprolol in real samples is reported. This potentiometric sensor was designed by dispersing the MIP
particles in dioctylphthalate plasticizer as solvent mediator and then embedded in polyvinyl chloride matrix. The electrode
of
exhibited a near-Nernstian slope of 55.4 ± 1 mV decade-1 for metoprolol over a wide concentration range between 2.0 × 10-7-8.0 ×
10-3 M and a detection limit of 1.3 × 10-7 M. With a response time of about 14 s it could be used for at least 6 months without any
divergence in potential. The proposed electrode can be used in the pH range of 3.5-10.5 and can reveal good selectivities for
metoprolol over a wide variety of ions. Finally, the designed sensor was successfully applied as an indicator electrode to
ive

determine the concentration of metoprolol in tablets, human urine and plasma. The results were compared favorably with those
obtained by HPLC method and showed satisfactory agreements with them.

Keywords: Metoprolol, Ion-selective electrode, Molecularly imprinted polymer, Coated graphite, PVC-Membrane
ch

O
INTRODUCTION O
O
O
Metoprolol is a selective β1 receptor blocker used in the OH
treatment of several diseases of the cardiovascular system,
Ar

O
especially hypertension. This drug is amongst the most widely
prescribed drugs in the world, based on the aryloxy- Methacrylic acid (MAA) Ethylene glycol
propranololamine backbone (Fig. 1) [1-3]. Various methods dimethacrylate (EGDMA)
have been developed for the determination of metoprolol
including gas chromatography [4,5], and high-performance
liquid chromatography (HPLC) with UV [6-8], fluorimetric
[9,10] and mass spectrometric detection [11]. The main N O
O
problems of employing chromatographic methods are the need H OH

for derivatisation and time-consuming extraction procedures. Metoprolol

Since the use of techniques entails relatively expensive
instrumentation and running costs, development of simpler, Fig. 1. Chemical structure of functional monomer (MAA),
cross-linking monomer (EGDMA) and imprint
*Corresponding author. E-mail: m.sabertehrani@yahoo.com molecule (metoprolol).

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 Saber Tehrani et al.

faster and less expensive, but still sensitive, electrochemical the sample, i.e., in comparison with other methods of trace
techniques could be an interesting alternative. analysis, these devices do not require any elaborate sample
Among reported investigations in the field of molecularly preparation including preconcentration or application of agents
imprinted polymers for β-blockers, there are only a few papers [30]. In the present work, we propose an MIP-based ion-
that are concerned with the metoprolol as template [12,13], selective electrode for the metoprolol present in tablets, human
and among the reported researches in the field of urine and plasma by casting a membrane after dispersing
electrochemical methods for β-blockers [14-17], there are metoprolol imprinted polymer particles in dioctylphthalate
only a few sources that are concerned directly with metoprolol (DOP) and embedding in polyvinyl chloride (PVC) matrix.
[17] and virtually no article is found to report on the detection

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of metoprolol using MIP based ion-selective electrode. On the EXPERIMENTAL
whole, one could say that there are only a few researches
dealing with potentiometric molecular sensors based on MIPs Reagents and Apparatus

SI
[18-25]. All chemicals were of analytical grades and all solutions
Molecular imprinting has been known as a polymerization were prepared in double-distilled water. Metoprolol tartrate
technique for the preparation of synthetic polymers with was obtained from SUN Pharmaceutical Industries LTD
recognition sites for given molecules [26]. Among the (Maharashtra, India). Methacrylic acid (MAA), ethylene
different methods available for the preparation of MIPs, the glycol dimethacrylate (EGDMA), chloroform, acetic acid,
of
so-called non-covalent approach, which uses only non- acetonitrile, methanol, hydrochloric acid, trifluoroacetic acid
covalent interactions between the template and the functional (TFA) triethylamine, sodium chloride and the nitrate salts of
monomers, is probably the most flexible regarding the all cations used (all from Merck), dibutyl phthalate (DBP),
selection of the functional monomers and the possible dioctyl phthalate (DOP), ortho-nitro phenyl octyl ether (o-
ive

template molecules. For these reasons, the non-covalent NPOE), poly(vinyl chloride) (PVC) (with high relative
approach has been the most widely adopted [27]. The molecular weight), oleic acid (OA) (all from Fluka), potassium
procedure for synthesizing an MIP is based on the chemical tetrakis (p-chlorophenyl) borate (KTpClPB), sodium
polymerization of a functional monomer and a cross-linking tetraphenyl borate (NaTPB) and 2,2′-azobisisobutyronitrile
ch

agent in the presence of a molecule used as a template. After (AIBN) (from Aldrich) were used as received.
the removal of the imprinted molecule, an imprinted polymer All potentials were measured on a digital Hioki 3200
is obtained. This polymer contains sites with a high affinity for multimeter vs. a Philips saturated calomel reference electrode
the template molecule, due to their shapes and the arrangement (SCE) at 25.0 ± 0.1 °C. The Fourier transform infrared (FTIR)
Ar

of the functional groups of the monomer units. The imprinted spectra of non-imprinted and molecularly imprinted polymers
polymers are used as antibody-like materials for high were obtained using a Nexus870 Thermo Nicolet FTIR
selectivity and sensitivity, owing to their long-term stability, spectrometer. A Shimadzu-UV-1700 PC controlled double-
chemical inertness and insolubility in water and most organic beam spectrophotometer equipped with quartz cell with a 1-
solvents [28]. cm path length was used for recording absorbances in the
This study is concerned with the construction of a comparative study with pharmacopoeia method [31]. HPLC-
potentiometric sensor prepared from MIP-based membrane comparative analysis was performed using a Perkin-Elmer 200
and its application for metoprolol determination in aqueous Series chromatographic workstation. These HPLC
medium. The re-emergence of ion-selective electrodes as a measurements were carried out on a C18 column. The mobile
strong research direction in the field of potentiometric sensors phase consisted of acetonitrile:methanol:0.5% acetic
is largely due to their improved mechanistic understanding acid:triethylamine (56:18:26:0.1, v/v) at a flow rate of 1.0 ml
[29]. Compared with other methods of trace analysis, min-1 [32]. The HPLC system was equilibrated for
potentiometry is an extremely inexpensive technique. approximately 30 min at the same flow rate before the analysis
Potentiometric sensors are known to only minimally perturb commenced. 20 µl of sample was injected manually with a

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 Molecularly Imprinted Polymer Based PVC-Membrane-Coated Graphite Electrode

100 μl syringe. The UV detection wavelength was 225 nm. long) were prepared from spectroscopic grade graphite. The
Chromatography was performed at ambient temperature and electrode was polished with fine alumina slurries on a
each analysis was repeated in triplicate. A model MP225 polishing cloth, sonicated in distilled water and dried in air. A
Mettler-Toledo pH-meter was used for the pH adjustments. shielded copper wire was glued to one end of the above
Stock solution of metoprolol (5.0 × 10-2 M) was prepared graphite rod with epoxy resin, and the electrode was sealed
by dissolving an appropriate amount of metoprolol tartrate in into the end of a PVC tube. The polished electrode was dipped
bidistilled water. Other dilute solutions (1.0 × 10-2 M-1.0 × into the membrane solution, and the solvent was evaporated. A
10-8 M) were prepared by serial dilution at constant ionic layer was formed on the graphite surface, which was allowed
strength (0.05 M NaCl) and all pHs were adjusted with HNO3 to set for 3 h. The electrode was finally conditioned for 18 h
by being soaked in a 1.0 × 10-4 M solution of metoprolol.

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or NaOH.

Preparation of Metoprolol MIP or Non-Imprinted Emf Measurements

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Polymer (NIP) Particles The following cell assembly was used for the measurement
The procedure for the synthesis of MIP and NIP polymers of all emfs:
was as follows: SCE||Sample solution|MIP-based membrane|Graphite
To be briefe, to a three-necked round-bottom flask were added electrode
template (metoprolol tartrate; 0.25 mmol, or 0.171 g or The coated electrode containing MIP was used as the
of
metoprolol; 0.5 mmol), functional monomer (MAA; 2 mmol, measuring electrode in conjunction with an SCE and the
or 0.17 ml), cross-linker (EGDMA; 10 mmol, or 1.89 ml) and activity coefficients were calculated according to the Debye-
initiator (AIBN; 0.25 mmol, or 0.042 g) in chloroform (20 ml). Huckel equation:
The mixture was purged with nitrogen for 10 min to remove
ive

any dissolved oxygen, which would inhibit free radical − 0.51z 2 μ

log γ =
polymerization. The polymerization was allowed to continue 1+ μ
in a water bath at 60 °C for 18 h. After polymerization, a hard
polymer monolith was obtained, which was crushed and where γ is the activity coefficient, μ and z are the ionic
ch

ground into a fine powder with a mortar and pestle. Soxhlet strength of the solution and charge of the ions, respectively.
extraction was performed to remove the template with 70:30
(V/V) methanol:acetic acid overnight. Then, the polymer was RESULTS AND DISCUSSION
washed several times with pure methanol to remove the acetic
Ar

acid and facilitate drying. The dried polymer was now ready Preparation and Characterization of MIP
for use. The method for the preparation of NIP was exactly It is noteworthy that in the preparation of many non-
similar to the procedure for the synthesis of MIP with the covalent MIPs a template:functional monomer:cross-linker
exception of metoprolol (imprint molecule) omitted in the molar ratio of about 1:4:20 has resulted in very suitable
preparation of NIP. performance characteristics [19,21,28,34-41]. Therefore, this
ratio was used for the synthesis of metoprolol molecularly
Electrode Preparation imprinted polymer in the present work. The most commonly
The general procedure used to prepare the PVC membrane used functional monomer is methacrylic acid (MAA). In
was similar to works reported by Sales and coworkers [20], addition to the strong ionic interactions that MAA can form
Rao and coworkers [21,22], and Shamsipur and coworkers with basic functional groups on the template, the carboxyl
[33]. Exactly 60 mg PVC was dissolved in 2.5 ml of THF. A group on this monomer is an excellent hydrogen bond donor
40 mg of MIP or NIP particles were dispersed in 0.2 ml of and acceptor [28]. The chemical environment and the
DOP which were added to the above solution and morphology of the MIP are greatly affected by the choice of
homogenized. Graphite electrodes (3 mm diameter and 10 mm cross-linking monomer, so that careful consideration must be

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 Saber Tehrani et al.

given to its choice. The most commonly used cross-linker beakers, and the pH value was adjusted to 6.00 with 0.1 M,
EGDMA has two acrylate groups that enable it to form more HNO3 or NaOH. Then 50 mg NIP or MIP adsorbent was
rigid polymers. This enhanced rigidity has been shown to lead added to each sample, and the mixtures were shaken
to MIPs with higher capacities and selectivities [28]. For vigorously for 30, 60, 90, 120, 150 and 180 min, respectively,
efficient template-monomer interactions, generally, aprotic to facilitate adsorption of the metoprolol onto the imprinted
organic solvents with low polarities are required. A solvent polymer particles. After the solutions were centrifuged, free
with such characteristics as chloroform leads to an MIP which concentration of metoprolol in the filtrate solutions was
will provide binding sites with higher fidelity and increased directly determined by spectrophotometry. It was found from
capacity [28]. Accordingly, we used MAA, EGDMA and the resulting data that the time period of 150 min incubation

D
chloroform as functional monomer, cross-linker and porogenic was enough to achieve equilibrium. The amount of metoprolol
solvent, respectively, for the synthesis of MIP. bound to the polymer was calculated by subtracting the
The control polymer (NIP) and molecularly imprinted amount of free substrate from the initial amount of the

SI
particles obtained using non-covalent imprinting protocol were template. The same procedure was followed for NIP particles.
subjected to characterization by FT-IR and binding batch static The phase distribution ratio (Kd) and adsorption capacity (Q)
methods. were calculated using the following equations:
FT-IR Spectra. The FT-IR spectra of control non-
Ci − C f V (1)
imprinted and molecularly imprinted polymer materials Kd = ×
of
Cf W
prepared using radical bulk polymerization are shown in Fig.
2. In the IR spectra, the absorptions due to carboxyl OH (C i − C f )V
Q= (2)
stretching (~3500 cm-1), carbonyl group stretching (~1730 W
cm-1), C-O stretching (~1260 cm-1) and C-H vibrations (~756,
ive

~1390, ~1460 and ~2956 cm-1) were observed. By evaluation where Ci and Cf represent the initial and equilibrium
and comparison of the spectra (A, B and C), the important concentration of metoprolol in the aqueous phase (mg ml-1), W
results obtained are as follows: is the weight of the polymer (g) and V is the volume of the
(1) The absorbances pertaining to metoprolol (spectrum C), aqueous phase (ml). Data from adsorption capacity studies
ch

stretching of aromatic C=C (~1512 cm-1), stretching of were substituted in Eqs. (1) and (2) and thus Kd and Q were
aromatic C-H (~1250 cm-1), C-N stretching (~1111 cm-1), calculated to be 307.8 ± 17.8 ml g-1 and 0.8 ± 0.04 mg g-1 for
bending of aromatic C-H (~821 cm-1) and combination bands MIP and 36.6 ± 2.9 ml g-1 and 0.114 ± 0.01 mg g-1 for NIP,
for para substitution (~1891 cm-1, ~2067 cm-1) aren’t observed respectively. By the evaluation of these data, it can be
Ar

in the MIP spectrum (B). This difference proves that imprint concluded that the adsorption of metoprolol onto NIP is based
molecule (metoprolol) has been sufficiently leached from MIP on non-specific interactions; consequently, Kd and Q
in the soxhlet extraction step. quantities of NIP are negligible in comparison to MIP. This
(2) The peak attributed to the C-H stretching of methylene can be related to the introduction of shape-selective binding
group (~2956 cm-1), carbonyl group stretching (~1730 cm-1), sites into three-dimensional polymeric network of MIP.
C-O stretching (~1260 cm-1) and C-H bending of -CH2 (~1460
cm-1) for the MIP were relatively stronger than those of NIP. Optimal Membrane Composition
Therefore, it can be concluded that the presence of imprint In chemical sensors and biosensors, a chemical or physical
molecule (metoprolol) causes increased incorporation of signal is generated upon binding of the analyte to the
ethylene glycol dimethacrylate into the polymer during the recognition elements: a transducer then translates this signal
preparation step. into a quantifiable output signal. The same general principle
Binding experiment by batch static method. Six portions applies if a molecularly imprinted polymer is used as the
of standard or sample solutions (100 ml) containing recognition element instead of a biomolecule [18]. The
metoprolol (0.3 mg) were individually transferred into 250 ml possibility of developing ion-selective electrodes for a few

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 Molecularly Imprinted Polymer Based PVC-Membrane-Coated Graphite Electrode

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of
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Fig. 2. FT-IR spectra of NIP (a), MIP (b) and metoprolol tartrate (c) by KBr pellet method.

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drugs and herbicides with MIPs has recently opened up new constant of the membrane phase and the mobility of the
horizons for sensor technology [19-25]. It is well-known that attendant species [42], it is expected to play a fundamental
MIPs have binding sites that are complementary in size and role in determining the electrode characteristics. It was
shape to the imprint molecule. In other words, a molecular observed that among the three different solvent mediators
memory is introduced into the polymer, which is capable of used, the use of 69% DOP in the presence of 10% MIP (entry
selectively rebinding the analyte. In this paper, the optimal 3, Table 1) provided better sensitivity, with a slope of 49.2 ± 1
conditions for the best performance of metoprolol-selective mV decade-1. The results indicated that the membrane with o-
electrode based on a membrane containing MIP have been NPOE offered lower sensitivity in the range 1.0 × 10-7 M to
investigated systematically. 1.0 × 10-2 M. These findings signify that the plasticizers with

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It is well-known that the important features of the PVC low dielectric constants, i.e., DOP (ε = 5.0) and DBP (ε = 8.5)
membrane such as the nature and amount of ion recognizing give better response characteristics compared to o-NPOE with
material, solvent mediator (plasticizer) and especially, the high dielectric constant of 24.0. Observation of better response

SI
nature of the additives significantly influence the sensitivity in the case of the membranes containing DOP is most likely
and selectivity of ion-selective electrodes [42,43]. Thus, due to highly energetic ionic interactions that can occur
different aspects of the membrane based on synthesized between carboxylic groups of the binding sites and positively
imprinted polymer were optimized whose results are charged metoprolol in this plasticizer with its lowest dielectric
summarized in Table 1. constant.
of
Since the nature of the plasticizer influences the dielectric The influence of MIP quantity and MIP/PVC ratio in the

Table 1. Effect of Membrane Composition on Response of the MIP-Based Metoprolol Electrode

ive

Membrane Composition (%) Slope

no. MIP PVC o-NPOE DBP DOP KTpClPB NaTPB OA (mV decade-1) a
ch

1 10 21 69 - - - - - 19.8

2 10 21 - 69 - - - - 34.7
3 10 21 - - 69 - - - 49.2
Ar

4 4 22 - - 74 - - - 18.1
5 7 22 - - 71 - - - 35.9
6b 13 20 - - 67 - - - 54.3
7 16 19 - - 65 - - - 41.5
8 19 19 - - 62 - - - Unstable
9 12 20 - - 68 - - - 52.4
10 15 20 - - 65 - - - 55.1
11 13 20 - - 65 2 - - 54.8
12 13 19 - - 64 4 - - 55.9
13 13 20 - - 65 - 2 - 45.2
14 13 19 - - 64 - 4 - 45.7
15 13 20 - - 65 - - 2 40.3
16 13 19 - - 64 - - 4 40.6
a
Concentration range = 1.0 × 10-7-1.0 × 10-2 M; pH of solutions = 6. bOptimum composition.

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 Molecularly Imprinted Polymer Based PVC-Membrane-Coated Graphite Electrode

membrane was investigated, whose results are shown in Table 120

1 (entries 3-10). The sensitivity of the electrode increased with 100
increasing MIP content until a value of 15% and MIP/PVC
80 b
ratio of 0.75 was reached. Further addition of MIP, however,

E (mV)
60
resulted in some decrease of the electrode response, most
40 a
probably due to some inhomogeneities and possible saturation
of the membrane [44]. 20

It should be noted that, even though the addition of the 0

KTpClPB resulted in responses that were closer to the additive 0 40 80 120 160 200 240 280

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free membrane, the selectivity coefficients of the membranes Time (s)

11 and 12 (with incorporated KTpClPB) were somehow Fig. 3. Response time of the metoprolol selective electrode
larger. Therefore, the additive free electrode based on with two isolated jumps in concentration; (a) 5.0 × 10-5

SI
membrane 6 was selected as the optimum membrane. M to 5.0 × 10-4 M, (b) 5.0 × 10-4 M to 5.0 × 10-3 M.

Concentration of Conditioning Solution

The proposed membrane electrode was further examined 60
with different concentrations of conditioning solution from 1.0 50
of
40
× 10-3 M to 1.0 × 10-5 M. Functioning of the membrane sensor
30
E (mV)

with the solution of various metoprolol tartrate concentrations 20

was found to cause no significant difference in the intercept of 10
the resulting potential-log Cmetoprolol plots. However, in the 0
ive

-10
case of 1.0 × 10-4 M more stable responses were obtained
-20
compared to 1.0 × 10-3 M and 1.0 × 10-5 M. Thus, a 1.0 × 10-4 0 100 200 300 400 500 600
Time (s)
M concentration of the conditioning solution was quite
appropriate for a smooth functioning of the membrane Fig. 4. Reversibility of the metoprolol selective electrode in
ch

electrode system. It should be noted that the optimum several high-to-low sample cycles (5.0 × 10-4 M to
equilibrium time for the membrane sensor was found to be 18 5.0 × 10-5 M).
h, after which stable potentials were generated in contact with
the metoprolol solutions.
Ar

sample concentrations the results of which are shown in Fig.

Response Time and Reversibility 4. It could be seen that the potentiometric response of the
In this study, the practical response time or the average sensor was reversible, although the time needed to reach the
time required for the metoprolol sensor to reach 90% of the equilibrium values was longer than that for the low-to-high
maximum potential was recorded after immersion into sample concentration procedure. It is well-documented that, in
metoprolol solutions with a 10-fold difference in concentration the case of high-to-low concentrations, the time needed to
(Fig. 3; two isolated jumps in concentration, 5.0 × 10-5 M to attain a stable potential was some 100 times longer than that
5.0 × 10-4 M and 5.0 × 10-4 M to 5.0 × 10-3 M) [42]. As can be required for the case of low-to-high concentrations (for a 10
seen, it was found that the electrode reached to its equilibrium times change in the concentration) [42].
response in 14 s. The other points after the time to reach
equilibrium potential indicated that reproducibility of the Effect of pH
electrode response was acceptable even during longer periods The pH dependence of the membrane sensor was tested
(up to 300 s). To evaluate the reversibility of the electrode, the over the pH range 2.0-12.0 at 1.0 × 10-4 M and 1.0 × 10-5 M
measurements were performed in the sequence of high-to-low metoprolol concentrations (Fig. 5). Adjustments of pH were

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150
80 100
b 50 b
40
E (mV)

E (mV)
0
0 -50
-100 a
-40
a -150
-80 -200
0 2 4 6 8 10 12 -8 -7 -6 -5 -4 -3 -2 -1
pH log[metoprolol]

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Fig. 5. Effect of pH of test solution on the potential response Fig. 6. Calibration plot for the proposed metoprolol selective
of the metoprolol selective sensor at (a) 1.0 × 10-5 M electrode with optimized membrane composition
and (b) 1.0 × 10-4 M metoprolol concentrations. based on NIP (a) and MIP (b) particles.

made with nitric acid or sodium hydroxide solutions. As is

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with the metoprolol.
The emf response of the MIP-based membrane at varying
of
seen from Fig. 5, potentials stay constant from pH 3.5 to 10.5,
beyond which potential drifts are observed. Thus, this range concentrations of the metoprolol (Fig. 6) indicates a rectilinear
was taken as the working pH range of the proposed sensor and range from 2.0 × 10-7 M to 8.0 × 10-3 M. The slopes of the
pH 6.0 was selected for the measurements. This behavior of calibration curves were 55.4 ± 1 mV per decade of the
the prepared membrane could be interpreted as follows: metoprolol concentration. The limit of detection, as
ive

(1) The pKa of metoprolol is about 9.5 [45-47], i.e., the determined from the intersection of the two extrapolated
observed potential drift at high pH values (pH > 10.5) could be segments of the calibration graph, was 1.3 × 10-7 M. The
due to the formation of metoprolol in non-ionic form. electrodes exhibit a stable potential response and almost
(2) Below pH 3.5, the membrane may respond to H+ as a unchanged metoprolol selectivity for at least 6 months.
ch

consequence of which an increase in the potentials was

observed. Potentiometric Selectivity
The influence of interfering ions on the response behavior
Calibration Curve of ion-selective membrane electrodes is usually described in
Ar

After the optimization of the membrane composition, we terms of selectivity coefficients. The potentiometric selectivity
continued to prepare a membrane with NIP using the same coefficients, K Met
Pot . of the NIP and MIP-membrane sensors
., J

amount of the active material (13%) and compared the were evaluated by the separate solutions method [48,49]. As
electrode performance of both polymers. The typical potential could be seen from Table 2, the selectivity coefficients
response curves of the sensors based on NIP and MIP to obtained for the examined species indicated that most of these
metoprolol in the concentration range of 5.0 × 10-8 M to 5.0 × compounds did not disturb the functioning of the metoprolol-
10-2 M are shown in Fig. 6. The figure illustrates that a selective electrode significantly. As previously mentioned,
specific response to metoprolol could be observed with MIP non-specific interactions could occur in both MIP and NIP
but not with NIP, suggesting that the molecular imprinting was materials in comparison to specific shape-selective
more effective for metoprolol sensing than for the NIP. A interactions. The carboxyl groups on the surface of MIP and
slope of ~23 mV decade-1 for the membrane based on NIP in NIP particles are the origin of non-specific interactions. Based
the concentration range of 5.0 × 10-6 M to 1.0 × 10-3 M on these findings, it is clear that the selectivities of the
metoprolol is most probably due to the carboxyl groups on the electrodes based on MIP and NIP are comparable for most of
polymer surface which could have a non-specific interaction the ionic species.

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 Molecularly Imprinted Polymer Based PVC-Membrane-Coated Graphite Electrode

Pot .
Table 2. Selectivity Coefficient Values ( K Met ., J
) of the Proposed Electrodes Based on the MIP (I) and NIP (II) Particles

Pot . Pot .
K Met ., J K Met ., J
Interferent (J) Interferent (J)
I II I II
Urea 3.6 × 10-5 7.7 × 10-4 Mg2+ 8.3 × 10-5 1.3 × 10-4
Benzoic acid 2.7 × 10-2 8.3 × 10-2 Ca2+ 1.8 × 10-4 2.9 × 10-4
Oxalic acid 2.1 × 10-1 9.9 × 10-1 Ba2+ 3.2 × 10-5 5.1 × 10-5
Glucose 6.9 × 10-6 2.3 × 10-4 Pb2+ 3.4 × 10-4 3.6 × 10-3

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Na+ 9.5 × 10-4 1.1 × 10-3 Cu2+ 9.9 × 10-5 4.7 × 10-4
K+ 5.1 × 10-4 4.1 × 10-4 Ni2+ 2.2 × 10-3 7.1 × 10-3
NH4+ 7.5 × 10-4 8.5 × 10-4 Zn2+ 1.1 × 10-3 5.2 × 10-3

PRELIMINARY APPLICATIONS

SI 150

100
of
Potentiometric Titration 50
E (mV)

It should be noted that the metoprolol-selective membrane

0
electrode introduced here could be used for the indirect
-50
(titration) and direct potentiometric determination of the
ive

metoprolol ions. We successfully applied the MIP-based -100

0 0.5 1 1.5 2 2.5 3
electrode as an indicator in the potentiometric titration of 25
ml NaTPB
ml of 0.005 M metoprolol against 0.1 M sodium tetraphenyl
borate solution. It is well-known that metoprolol as a Fig. 7. Potentiometric titration curve of 25 ml of 0.005 M
ch

secondary amine reacts with tetraphenylborate to form a metoprolol solution with 0.1 M NaTPB, using the
precipitate ion-pair product [50]. The resulting titration curve proposed sensor as an indicator electrode.
is shown in Fig. 7, indicating that the amount of metoprolol in
solution could be determined with the proposed electrode.
Ar

concentration of metoprolol in the final solution was within

®
Determination of Metoprolol Tartrate in Metoral the working range, and then analyzed by the proposed MIP
Tablet electrode. The metoprolol tartrate content of the metoral®
We successfully applied the introduced metoprolol- tablet was found to be 49.1 ± 1.8 mg per tablet by the
selective membrane electrode for the direct determination of proposed potentiometric method. This accorded satisfactorily
metoprolol tartrate in the metoral® tablets obtained from a with those obtained by pharmacopoeia method [31] (48.1 ±
local pharmaceutical shop. These tablets are composed of 1.4 mg) and HPLC analysis [32] (48.7 ± 0.9 mg).
metoprolol tartrate (50 mg per tablet) and some common
excipients. Ten tablets were finely ground, homogenized and a Recoveries of Spiked Metoprolol in Human Urine
portion of the powder (0.1812 g, average tablet mass) was and Plasma Samples
weighed accurately, transferred into a 500 ml volumetric flask The high degree of metoprolol selectivity exhibited by the
and diluted with water. The mixture was sonicated for at least membrane electrode makes it potentially useful for monitoring
15 min to aid dissolution and then filtered. A 10 ml of the concentration level of metoprolol in real samples. In this
filtrate was diluted further to 50 ml with water so that the regard, experiments were performed to determine the

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Table 3. Recoveries of Spiked Metoprolol in Human Urine and Plasma Samples

Metoprolol added Metoprolol found Recovery (%)a

Sampleb
(µg) (µg) Proposed method HPLC
Urine
150.0 152.4 101.6 (3.8) 102.8 (2.3)

Plasma
150.0 153.3 102.2 (4.1) 103.9 (2.1)
a
Average of three measurements with RSD% in parenthesis. bSample volumes for the proposed method were 50
ml.

D
SI
feasibility of using the electrode to measure metoprolol in applicability of the proposed sensor was examined by the
human urine and plasma samples. determination of metoprolol in tablets and recovery tests of
Blood samples (5 ml) were collected in heparin-containing metoprolol added to human urine and plasma samples.
tubes, protected from light and kept at 4 °C. Plasma was
obtained after blood centrifugation at 1800 g for 5 min and ACKNOWLEDGEMENTS
of
was diluted ten times with water before potentiometric
measurements. Urine sample (10 ml) was deproteinated with The authors gratefully acknowledge the support of this
TFA (100 μl), vortexed for 3 min, and centrifuged for 5 min at research by the Analytical Chemistry laboratory, Laboratory
1500 g. The treated sample was diluted 100 times with water Research Complex, Science & Research Branch, Islamic Azad
ive

prior to potentiometric measurement by the proposed method. University, Tehran. Iran.

The results of the recovery tests are summarized in Table 3.
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