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Molecularly imprinted polymer-based bulk optode for the determination of itopride hydrochloride in physiological fluids
Author’s Accepted Manuscript Molecularly Imprinted Polymer-Based Bulk Optode for the Determination of Itopride Hydrochloride in Physiological Fluids F.M. Abdel-Haleem, Adel Madbouly, R.M. El Nashar, N.T. Abdel-Ghani www.elsevier.com/locate/bios
PII: DOI: Reference:
S0956-5663(16)30511-5 http://dx.doi.org/10.1016/j.bios.2016.05.081 BIOS8771
To appear in: Biosensors and Bioelectronic Received date: 15 February 2016 Revised date: 16 May 2016 Accepted date: 24 May 2016 Cite this article as: F.M. Abdel-Haleem, Adel Madbouly, R.M. El Nashar and N.T. Abdel-Ghani, Molecularly Imprinted Polymer-Based Bulk Optode for the Determination of Itopride Hydrochloride in Physiological Fluids, Biosensors and Bioelectronic, http://dx.doi.org/10.1016/j.bios.2016.05.081 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Molecularly Imprinted Polymer-Based Bulk Optode for the Determination of Itopride Hydrochloride in Physiological Fluids F.M. Abdel-Haleem*, Adel Madbouly, R.M. El Nashar*, N.T. Abdel-Ghani Chemistry Department, Faculty of Science, Cairo University, Gamaa Street, 12613, Giza, Egypt [email protected] [email protected] *Corresponding authors.
Abstract We report here for the first time on the use of Molecularly Imprinted Polymers as modifiers in bulk optodes, Miptode, for the determination of a pharmaceutical compound, itopride hydrochloride as an example in a concentration range of 1x10
-1
– 1x10-4 mole L-1. In
comparison to the optode containing the ion exchanger only (Miptode 3), the optode containing the ion exchanger and the MIP particles (Miptode 2) showed improved selectivity over the most lipophilic species, Na+ and K+, by more than two orders of magnitude. For instance, the optical selectivity coefficients using Miptode 2,
, were as follow:
-6;
= -4.0 which
were greatly enhanced in comparison with that obtained by Miptode 3. This work opens a new avenue for using miptodes for the determination of all the pharmaceutical preparations without the need for the development of new ionophores. Keywords Molecularly Imprinted Polymer; Bulk Optode; Itopride hydrochloride; Miptode
1
Bulk optodes are among the most powerful analytical techniques that could be used for determination of different analytes (Buhlmann et.al., 1998). This wide spread of optodes is due to their numerous advantages including low detection limit, pH cross sensitivity which facilitates different concentration ranges of application, determination of analytes of different charges, internal filling solution is not needed unlike their PVC ion-selective electrode counterpart, besides their simplicity in preparation, cost effectiveness, applicability in routine analysis, and many others (Bakker et.al., 1997). During the last two decades , molecularly imprinted polymers (MIPs), has grassped attention as due to their vast application in many techniques based on their excellent advantages, including their high selectivity and affinity to their target compounds, high mechanical and chemical stability and inertness, and being insoluble in water and most organic solvents. In addition, they can be easily prepared, cost effectiveness and applicability in harsh chemical media, temperature or pressure (Abdel Ghani et al., 2016; Li et.al., 2012; Lv et.al., 2103). Merging between MIPs and optodes, produced powerful application, Miptode, that combines the advantages of both and can be used for several applications (Narayanaswamy and Wolfbeis, 2004). It is prescribed for the treatment of gastrointestinal symptoms caused by reducing gastrointestinal motility, feeling of gastric fullness, upper motility, upper abdominal pain, anorexia, heartburn, nausea and vomiting and non-ulcer dyspepsia or chronic gastritis. We report here for the first time on the use of MIP-based optode impregnated with chromoionophore for the determination of itopride hydrochloride (Fig. S1), as an example, in physiological fluids. The Miptode works in the absorption mode which facilitates its application with very low cost. Itopride hydrochloride (Itoh) is chemically designed
as
(N-[4-[2-(dimethylamino)
ethoxy
benzyl]-3,4-dimethoxybenzamide
hydrochloride) (Sweetman S.C., 2007). Itopride is one of the prokinetic agents; it has anticholinesterase activity, as well as, dopamine D2 receptor antagonist activity (Iwanaga Y., 1994). It is prescribed for the treatment of gastrointestinal symptoms caused by reducing gastrointestinal motility, feeling of gastric fullness, upper motility, upper abdominal pain, anorexia, heartburn, nausea and vomiting and non-ulcer dyspepsia or chronic gastritis. 2
MIP was prepared with different ratios of methacrylic acid (MAA) (Abdel Ghani et al., 2016), and that with the highest binding capacity was chosen as recognition material for the fabrication of new PVC sensors and their responses were compared with each other. The suggested sensors showed Nernstian slopes in the concentration range of 1.0×10-2 1.0×10-5 mole L-1 with a detection limit of 2.81×10-6 , 6.30×10-6 mole L-1 for sensors x ( containing 1% MIP) and y ( containing 1% MIP and 1 % ionic additive) (Abdel Ghani et al., 2016), respectively. Based on the results of ISEs for itopride based on its MIP, best compositions were tested for the construction of the Miptode, Table 1. Briefly, Miptodes were prepared as described by F.M. Abdel-Haleem by weighing and dissolving the different components (Table 1) in 3 mL tetrahydrofuran (THF) in a petri-dish with continuous stirring for 10 minutes and the cocktail was cast onto a dust-free quartz slides (0.9x4 cm2, 1mm thickness), then membranes were dried in air for about 10 minutes to form miptode and stored in the dark when not in use. The resulting films had thickness in the range of 4-9 μm (F.M. Abdel-Haleem). Absorbance measurements were performed by placing the miptode in a quartz cuvette (1x1x4 cm3) containing drug solution of different concentrations. Itopride test solutions were prepared using different buffers. Optodes were conditioned in the selected buffer for 20 min before the first measurement was made (F.M. Abdel-Haleem). Miptode no.1 showed good response for the itopride hydrochloride, within 3 minutes response time in low concentration range, 1.0x10-6-1.x10-4 mole L-1, with limit of detection 1.0x10-6 mole L-1. This can be due to the absence of the inner filling solution in case of optodes, which is a great advantage for optodes. The response mechanism of the Miptode is similar to that of the ionophore-based optodes where the MIP particles act as the ionophore that responsible for the selective binding of the analyte molecules (Abdel Ghani et.al., 2016) with concomitant deprotonation of the chromionophore ETH7075, which leads to the increase of the absorbance at 525 nm and its decrease at 470nm. The sensing mechanism can be represented by the equation: 3
CHm + Lm+ Where CHm and
--------------------→
represent the protonated and deprotonated forms of the
chromoionophore ETH7075 in the membrane phase, L m and MIP particles in the free and complexed states, and
represent the neutral represent the protons and
the itropride cation in the aqueous solution. The addition of sodium tetraphenyl borate (Na-TPB) has an influence on the response time, concentration range and detection limit (Buhlmann et.al., 1998); in Miptode 2, NaTPB caused increase in the concentration range by an order of magnitude in the higher concentrations with higher detection limit and the response time was increased to 5 minutes. This increase in the detection limit, concentration range of application may be due to the response mechanism which is not solely based on the molecular recognition of the MIP particles and the template analyte, but also is controlled by the ion-exchange process which is diffusion controlled by the Miptode composition and especially the plasticizer dielectric constant. However, this high detection limit of Miptode 2 can be lowered by increasing the amount of MIP particles, but this is not possible due to the solubility limitations of the MIP particles within membrane cocktail. Yet, other ways of changing the application concentration range might involve the use of different chromoionophore, pH of the medium and the type of plasticizer used (Buhlmann et.al., 1998).
Miptodes 3 and 4 were constructed for assisting the role of MIP in the response mechanism. Miptode 3 is free of MIp, while optode 4, includes the non- imprinted polymer (free of template ) NIP. The concentration ranges of application decreased for optodes 3 and 4, but the response time was increased also to 8 minutes in case of low concentrations and 3 minutes in high concentrations which ensures the importance of MIP particles in the Miptode to be used in routine work. The Miptode containing the MIP showed the best response as shown in Fig. 1. One of the important features of the optodes is its pH cross sensitivity. Miptode 2 response is tested at two different pH values, namely pH 4.5 and 5.5 using 0.02 mole L-1 acetate buffers, Fig S2. These values of the pHs ensures the existence of the Ip in its cationic species ( 4
pKa is 8.77) (Abdel Ghani, N.T., 2016). This shift from 4.5 to 5.5 causes the concentration range to be shifted to 1.0x10-5-1.0x10-3 mole L-1 with limit of detection 1.0x10-5 mole L-1. This is very important advantage of the optode which led to decrease in the detection limit. The other important feature of the optode is its selectivity. The selectivity of Miptode 2 for Ip was tested over the most lipophilic cations, sodium and ammonium, and compared to results of ion-exchange sensor, Miptode 3, and that of its counterpart ISE. The incorporation of the MIP particles within the optode cocktail caused improved selectivity of the sensor towards Ip over most interfering lipophilic species by more than three orders of magnitude in some cases and improved the selectivity over its ISE counterpart, Table 2. Also, the applicability of the proposed Miptode could be tested by measuring the concentration of Ip in spiked urine sample as an example. Miptode 2 was successfully applied to determine concentration as 1.2 ± 0.1 mmole L-1 for four measurements where the true value was 1.3 mmole L-1, with a Recovery of 97.2%. In conclusion, MIP-based bulk optode, Miptode, could be constructed and used for the first time for the determination of itopride hydrochloride in a reliable concentration range. The proposed Miptode, the mechanism was the same for ionophore-based optodes which responds to simple cations with concomitant deprotonation of the chromoionophore ETH7075 leading to decrease of the absorbance at 470nm. pH cross sensitivity was an advantage in terms of decreasing the detection limit. The optode showed very promising selectivity results over most lipophilic species in comparison to ion-exchanger optode and its counterpart ISE. The sensor was successfully applied for the determination of the itopride in spiked urine sample with high recovery %.
References Abdel Ghani, N.T., El Nashar, R. M., Abdel-Haleem, F. M., Madbouly, A., 2016 Electroanalysis, 2016, in press. Abdel-Haleem, F.M., 2016 sensors actuators B., 233, 257-262. Bakker, E., Buhlmann, P., Pretsch, E., 1997 Chem. Rev., 3083-3132. 5
Buhlmann, P., Pretsch, E., Bakker, E., 1998 Chem. Rev., 1593-1687. Iwanaga Y., Kimura T., Miyashita N., Morikawa K., Nagata O., Itoh Z., Kondo Y., 1994 Jpn. J. Pharmacol., 66, 317-322. Li, S., Ge, Y., Piletsky, S. A., Lunec, J., 2012 Molecularly Imprinted Sensors: Overview and Applications, Elsevier, Amsterdam. Lv, Y., Tan, T., Svec, F., 2013 Biotechnol. Adv. 31, 1172-1186. Narayanaswamy, R., Wolfbeis, O. S., 2004 Eds. Springer Ser. Chem. Sens. Biosens.; Springer-Verlag: Berlin, Germany, Vol.1. Sweetman, S. C., 2007 35th Eds. Martindale the Complete Drug Reference, Pharmaceutical Press, London, 2007.
Fig.1: Normalized Absorbance (α) of optode 2 (▼), optode 3 (○) and optode 4 (●) as a function of concentration of itopride hydrochloride using acetate buffer.
6
Table 1: Composition of the different MIP-based Optodes, its linear dynamic concentration range (C.R.) and detection limit (LOD.). No
PVCa TCPb MAAc Na-TPBd ETH 7075e C.R. (mole L-1)
1
0.032
0.065
0.001
-----
0.001
1.0x10-6-1.0x 10-4
2
0.032
0.065
0.001
0.001
0.001
1.0x 10-4-1.0x 10-1 1.0x10-4
3
0.032
0.065
-----
0.001
0.001
1.0x 10-5-1.0x 10-2 1.0x10-5
4
0.032
0.065
0.001e
0.001
0.001
1.0x 10-4-1.0x 10-2 1.0x10-4
a
Tricresyl phosphate plasticizer in mg;
Methacrylic acid molecularly imprinted polymer particles as ionophore in mg;
d
e
1.0x10-6
Poly (vinyl-chloride) in mg;
b
c
LOD (mole L-1)
Cation-exchanger, sodium tetrakis(trifluoromethyl) phenyl borate in mg;
Non-imprinted polymer (NIP) is used instead of MIP; in mg.
Table 2: Values of log
Na+
Optode 2
Optode 3
ISE
-4.0
-2.0
-2.5
7
<-6
-1.0
-3.0
Highlights
Molecularly Imprinted Polymers was used as modifiers in bulk optodes, Miptode. Miptode response was fully optimized. Miptode was applied successfully to the analysis of itopride in urine samples.
8
PII: DOI: Reference:
S0956-5663(16)30511-5 http://dx.doi.org/10.1016/j.bios.2016.05.081 BIOS8771
To appear in: Biosensors and Bioelectronic Received date: 15 February 2016 Revised date: 16 May 2016 Accepted date: 24 May 2016 Cite this article as: F.M. Abdel-Haleem, Adel Madbouly, R.M. El Nashar and N.T. Abdel-Ghani, Molecularly Imprinted Polymer-Based Bulk Optode for the Determination of Itopride Hydrochloride in Physiological Fluids, Biosensors and Bioelectronic, http://dx.doi.org/10.1016/j.bios.2016.05.081 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Molecularly Imprinted Polymer-Based Bulk Optode for the Determination of Itopride Hydrochloride in Physiological Fluids F.M. Abdel-Haleem*, Adel Madbouly, R.M. El Nashar*, N.T. Abdel-Ghani Chemistry Department, Faculty of Science, Cairo University, Gamaa Street, 12613, Giza, Egypt [email protected] [email protected] *Corresponding authors.
Abstract We report here for the first time on the use of Molecularly Imprinted Polymers as modifiers in bulk optodes, Miptode, for the determination of a pharmaceutical compound, itopride hydrochloride as an example in a concentration range of 1x10
-1
– 1x10-4 mole L-1. In
comparison to the optode containing the ion exchanger only (Miptode 3), the optode containing the ion exchanger and the MIP particles (Miptode 2) showed improved selectivity over the most lipophilic species, Na+ and K+, by more than two orders of magnitude. For instance, the optical selectivity coefficients using Miptode 2,
, were as follow:
-6;
= -4.0 which
were greatly enhanced in comparison with that obtained by Miptode 3. This work opens a new avenue for using miptodes for the determination of all the pharmaceutical preparations without the need for the development of new ionophores. Keywords Molecularly Imprinted Polymer; Bulk Optode; Itopride hydrochloride; Miptode
1
Bulk optodes are among the most powerful analytical techniques that could be used for determination of different analytes (Buhlmann et.al., 1998). This wide spread of optodes is due to their numerous advantages including low detection limit, pH cross sensitivity which facilitates different concentration ranges of application, determination of analytes of different charges, internal filling solution is not needed unlike their PVC ion-selective electrode counterpart, besides their simplicity in preparation, cost effectiveness, applicability in routine analysis, and many others (Bakker et.al., 1997). During the last two decades , molecularly imprinted polymers (MIPs), has grassped attention as due to their vast application in many techniques based on their excellent advantages, including their high selectivity and affinity to their target compounds, high mechanical and chemical stability and inertness, and being insoluble in water and most organic solvents. In addition, they can be easily prepared, cost effectiveness and applicability in harsh chemical media, temperature or pressure (Abdel Ghani et al., 2016; Li et.al., 2012; Lv et.al., 2103). Merging between MIPs and optodes, produced powerful application, Miptode, that combines the advantages of both and can be used for several applications (Narayanaswamy and Wolfbeis, 2004). It is prescribed for the treatment of gastrointestinal symptoms caused by reducing gastrointestinal motility, feeling of gastric fullness, upper motility, upper abdominal pain, anorexia, heartburn, nausea and vomiting and non-ulcer dyspepsia or chronic gastritis. We report here for the first time on the use of MIP-based optode impregnated with chromoionophore for the determination of itopride hydrochloride (Fig. S1), as an example, in physiological fluids. The Miptode works in the absorption mode which facilitates its application with very low cost. Itopride hydrochloride (Itoh) is chemically designed
as
(N-[4-[2-(dimethylamino)
ethoxy
benzyl]-3,4-dimethoxybenzamide
hydrochloride) (Sweetman S.C., 2007). Itopride is one of the prokinetic agents; it has anticholinesterase activity, as well as, dopamine D2 receptor antagonist activity (Iwanaga Y., 1994). It is prescribed for the treatment of gastrointestinal symptoms caused by reducing gastrointestinal motility, feeling of gastric fullness, upper motility, upper abdominal pain, anorexia, heartburn, nausea and vomiting and non-ulcer dyspepsia or chronic gastritis. 2
MIP was prepared with different ratios of methacrylic acid (MAA) (Abdel Ghani et al., 2016), and that with the highest binding capacity was chosen as recognition material for the fabrication of new PVC sensors and their responses were compared with each other. The suggested sensors showed Nernstian slopes in the concentration range of 1.0×10-2 1.0×10-5 mole L-1 with a detection limit of 2.81×10-6 , 6.30×10-6 mole L-1 for sensors x ( containing 1% MIP) and y ( containing 1% MIP and 1 % ionic additive) (Abdel Ghani et al., 2016), respectively. Based on the results of ISEs for itopride based on its MIP, best compositions were tested for the construction of the Miptode, Table 1. Briefly, Miptodes were prepared as described by F.M. Abdel-Haleem by weighing and dissolving the different components (Table 1) in 3 mL tetrahydrofuran (THF) in a petri-dish with continuous stirring for 10 minutes and the cocktail was cast onto a dust-free quartz slides (0.9x4 cm2, 1mm thickness), then membranes were dried in air for about 10 minutes to form miptode and stored in the dark when not in use. The resulting films had thickness in the range of 4-9 μm (F.M. Abdel-Haleem). Absorbance measurements were performed by placing the miptode in a quartz cuvette (1x1x4 cm3) containing drug solution of different concentrations. Itopride test solutions were prepared using different buffers. Optodes were conditioned in the selected buffer for 20 min before the first measurement was made (F.M. Abdel-Haleem). Miptode no.1 showed good response for the itopride hydrochloride, within 3 minutes response time in low concentration range, 1.0x10-6-1.x10-4 mole L-1, with limit of detection 1.0x10-6 mole L-1. This can be due to the absence of the inner filling solution in case of optodes, which is a great advantage for optodes. The response mechanism of the Miptode is similar to that of the ionophore-based optodes where the MIP particles act as the ionophore that responsible for the selective binding of the analyte molecules (Abdel Ghani et.al., 2016) with concomitant deprotonation of the chromionophore ETH7075, which leads to the increase of the absorbance at 525 nm and its decrease at 470nm. The sensing mechanism can be represented by the equation: 3
CHm + Lm+ Where CHm and
--------------------→
represent the protonated and deprotonated forms of the
chromoionophore ETH7075 in the membrane phase, L m and MIP particles in the free and complexed states, and
represent the neutral represent the protons and
the itropride cation in the aqueous solution. The addition of sodium tetraphenyl borate (Na-TPB) has an influence on the response time, concentration range and detection limit (Buhlmann et.al., 1998); in Miptode 2, NaTPB caused increase in the concentration range by an order of magnitude in the higher concentrations with higher detection limit and the response time was increased to 5 minutes. This increase in the detection limit, concentration range of application may be due to the response mechanism which is not solely based on the molecular recognition of the MIP particles and the template analyte, but also is controlled by the ion-exchange process which is diffusion controlled by the Miptode composition and especially the plasticizer dielectric constant. However, this high detection limit of Miptode 2 can be lowered by increasing the amount of MIP particles, but this is not possible due to the solubility limitations of the MIP particles within membrane cocktail. Yet, other ways of changing the application concentration range might involve the use of different chromoionophore, pH of the medium and the type of plasticizer used (Buhlmann et.al., 1998).
Miptodes 3 and 4 were constructed for assisting the role of MIP in the response mechanism. Miptode 3 is free of MIp, while optode 4, includes the non- imprinted polymer (free of template ) NIP. The concentration ranges of application decreased for optodes 3 and 4, but the response time was increased also to 8 minutes in case of low concentrations and 3 minutes in high concentrations which ensures the importance of MIP particles in the Miptode to be used in routine work. The Miptode containing the MIP showed the best response as shown in Fig. 1. One of the important features of the optodes is its pH cross sensitivity. Miptode 2 response is tested at two different pH values, namely pH 4.5 and 5.5 using 0.02 mole L-1 acetate buffers, Fig S2. These values of the pHs ensures the existence of the Ip in its cationic species ( 4
pKa is 8.77) (Abdel Ghani, N.T., 2016). This shift from 4.5 to 5.5 causes the concentration range to be shifted to 1.0x10-5-1.0x10-3 mole L-1 with limit of detection 1.0x10-5 mole L-1. This is very important advantage of the optode which led to decrease in the detection limit. The other important feature of the optode is its selectivity. The selectivity of Miptode 2 for Ip was tested over the most lipophilic cations, sodium and ammonium, and compared to results of ion-exchange sensor, Miptode 3, and that of its counterpart ISE. The incorporation of the MIP particles within the optode cocktail caused improved selectivity of the sensor towards Ip over most interfering lipophilic species by more than three orders of magnitude in some cases and improved the selectivity over its ISE counterpart, Table 2. Also, the applicability of the proposed Miptode could be tested by measuring the concentration of Ip in spiked urine sample as an example. Miptode 2 was successfully applied to determine concentration as 1.2 ± 0.1 mmole L-1 for four measurements where the true value was 1.3 mmole L-1, with a Recovery of 97.2%. In conclusion, MIP-based bulk optode, Miptode, could be constructed and used for the first time for the determination of itopride hydrochloride in a reliable concentration range. The proposed Miptode, the mechanism was the same for ionophore-based optodes which responds to simple cations with concomitant deprotonation of the chromoionophore ETH7075 leading to decrease of the absorbance at 470nm. pH cross sensitivity was an advantage in terms of decreasing the detection limit. The optode showed very promising selectivity results over most lipophilic species in comparison to ion-exchanger optode and its counterpart ISE. The sensor was successfully applied for the determination of the itopride in spiked urine sample with high recovery %.
References Abdel Ghani, N.T., El Nashar, R. M., Abdel-Haleem, F. M., Madbouly, A., 2016 Electroanalysis, 2016, in press. Abdel-Haleem, F.M., 2016 sensors actuators B., 233, 257-262. Bakker, E., Buhlmann, P., Pretsch, E., 1997 Chem. Rev., 3083-3132. 5
Buhlmann, P., Pretsch, E., Bakker, E., 1998 Chem. Rev., 1593-1687. Iwanaga Y., Kimura T., Miyashita N., Morikawa K., Nagata O., Itoh Z., Kondo Y., 1994 Jpn. J. Pharmacol., 66, 317-322. Li, S., Ge, Y., Piletsky, S. A., Lunec, J., 2012 Molecularly Imprinted Sensors: Overview and Applications, Elsevier, Amsterdam. Lv, Y., Tan, T., Svec, F., 2013 Biotechnol. Adv. 31, 1172-1186. Narayanaswamy, R., Wolfbeis, O. S., 2004 Eds. Springer Ser. Chem. Sens. Biosens.; Springer-Verlag: Berlin, Germany, Vol.1. Sweetman, S. C., 2007 35th Eds. Martindale the Complete Drug Reference, Pharmaceutical Press, London, 2007.
Fig.1: Normalized Absorbance (α) of optode 2 (▼), optode 3 (○) and optode 4 (●) as a function of concentration of itopride hydrochloride using acetate buffer.
6
Table 1: Composition of the different MIP-based Optodes, its linear dynamic concentration range (C.R.) and detection limit (LOD.). No
PVCa TCPb MAAc Na-TPBd ETH 7075e C.R. (mole L-1)
1
0.032
0.065
0.001
-----
0.001
1.0x10-6-1.0x 10-4
2
0.032
0.065
0.001
0.001
0.001
1.0x 10-4-1.0x 10-1 1.0x10-4
3
0.032
0.065
-----
0.001
0.001
1.0x 10-5-1.0x 10-2 1.0x10-5
4
0.032
0.065
0.001e
0.001
0.001
1.0x 10-4-1.0x 10-2 1.0x10-4
a
Tricresyl phosphate plasticizer in mg;
Methacrylic acid molecularly imprinted polymer particles as ionophore in mg;
d
e
1.0x10-6
Poly (vinyl-chloride) in mg;
b
c
LOD (mole L-1)
Cation-exchanger, sodium tetrakis(trifluoromethyl) phenyl borate in mg;
Non-imprinted polymer (NIP) is used instead of MIP; in mg.
Table 2: Values of log
Na+
Optode 2
Optode 3
ISE
-4.0
-2.0
-2.5
7
<-6
-1.0
-3.0
Highlights
Molecularly Imprinted Polymers was used as modifiers in bulk optodes, Miptode. Miptode response was fully optimized. Miptode was applied successfully to the analysis of itopride in urine samples.
8