**4. Selecting plasticizers for anionic surfactant sensitive potentiometric sensors**

The surfactants are compounds essential to the modern civilization and technology. Determination and monitorization of the surfactants concentration is necessary in the

Use of Plasticizers for Electrochemical Sensors 133

concentration range of 10-5 to 10-2 M (Masadome et al., 2004). The three electrodes other than the NPOE - plasticized PVC membrane electrode showed a similar performance to that of the NPOE - plasticized PVC membrane electrode concerning low detection limits and slope sensitivity. The four electrodes examined in this study are excellently selective for the dodecyltrimethylammonium ion over inorganic anions, but interference from other cationic surfactants such as tetradecyltrimethylammonium ions is significant. With respect to slope sensitivity, selectivity, response time and pH effect, the four electrodes showed a similar performance. The use of NPOE derivatives as the more hydrophobic plasticizers in comparison to NPOE enhanced the performance of surfactant-selective PVC membrane electrodes with no added ion-exchanger with respect to low detection limits. On the other hand, the use of NPOE derivatives did not enhance the performance of surfactant - selective PVC membrane electrodes with respect to slope sensitivity,

The cyclam derivative 1,4,8,11-tetra(*n*-octyl)-1,4,8,11-tetraazacyclotetradecane (L) has been used as carrier for the preparation of PVC-based membrane ion-selective electrodes for anionic surfactants (Lizondo-Sabater et al, 2008). Different membranes were prepared using L as ionophore, tetra *n*-octylammonium bromide (TOAB) as cationic additive and dibutyl phthalate (DBP) or *o*-nitrophenyl octyl ether (NPOE) as plasticizers. The final used electrode contained a membrane of the following composition: 56% DBP, 3.4% ionophore, 3.8% TOAB and 36.8% PVC. This electrode displays a Nernstian slope of −60.0 ± 0.9 mV/decade in a 2.0 × 10−3 to 7.9 × 10−6 mol dm−3 concentration range and a limit of detection of 4.0 × 10−6 mol dm−3. The electrode can be used for 144 days without showing significant changes in the value of slope or working range. The electrode shows a selective response to dodecyl sulfate (DS−) and a poor response to common inorganic cations and anions. The selective sequence found was DS− > ClO4− >HCO3− > SCN− >NO3 <sup>−</sup> ≈CH3COO<sup>−</sup> ≈I− >Cl− >Br− > IO3<sup>−</sup> ≈NO2<sup>−</sup>

hydrophilic anion bicarbonate. Most of the potentiometric coefficients determined are relatively low indicating that common anions would not interfere in the DS− determination. A complete study of the response of the electrode to a family of surfactant was also carried out. The electrode showed a clear anionic response to DS− and to Na-LAS (sodium alkylbezenesulfonate) and a much poorer response to other anionic surfactants and to nonionic surfactants. Also the electrode shows certain non-linear cationic response in the presence of cationic and zwitterionic surfactants. The electrode was used for the determination of anionic surfactants in several mixtures, and the results obtained were

**5. Selecting plasticizers for the construction of ion-selective electrodes used** 

Potentiometry with ion-selective electrodes is one of the most useful analytical tools capable of measuring both inorganic and organic substances in pharmaceutical products (Kulapina & Barinova, 1997). At present, most works are devoted to establishing the factors providing desired modification of the properties of ion-selective membranes (Kulapina & Barinova, 1997). In this context, interesting results were reported on the effects of the ion association and the character of a plasticizing solvent on the selective properties of counter electrodes for the organic cations of drugs. It was suggested that the factor of ion association can be

compared to those found using a commercially available sensor.

**in pharmaceutical products analysis** 

<sup>2</sup>− >C2O42− >SO42−, i.e. basically following the Hoffmeister series except for the

selectivity, response time or pH effect.

≈SO32− > HPO4

production of detergents, in the industrial processes where anionic surfactants are used, in quality control of products containing added surfactants and in environment surveillance activities, especially monitoring water quality. In the last decades there have been created and improved numerous analytic methods for determination of anionic surfactants. Among these, there are the potentiometric methods based on potentiometric sensors (electrodes sensible to anionic surfactants). These are very attractive tools due to their good precision, relatively simple manufacturing, relatively low cost and their ability to determine the surfactants in the samples without previous separation steps (Mihali, 2006). The use of surfactant sensitive electrodes with plasticized polymeric membrane for the potentiometric determination of low concentrations of anionic surfactants has been described in several papers (Lizondo-Sabater et al, 2008; Matesic-Puac et. Al, 2005; Mihali et al., 2009; Nemma et al., 2009; Oprea et al. 2007 etc.)

The selection of the most suitable plasticizer for the ion selective electrodes sensible to lauril sulfate anion based on ion-association complexes of quaternary ammonium cation and surfactant anion was made by testing the behavior of poly(vinyl chloride) membrane composition with two ionophores (Mihali et al., 2009) : cetyltrimethylammonium laurylsulfate (CTMA-LS) and tricaprylmethylammonium laurylsulfate (TCMA-LS). As plasticizers were used tricresylphosphate (TCF), ortho-nitrophenyloctylether (NPOE) and dioctylsebaccate (DOS). Comparing the electrodes prepared from the point of view of the linear response range and the slope (Table 1) we can notice that the best performances have been obtained with the CTMA-LS ionophore based electrode, plasticized with DOS (slope 59.39 mV/concentration decade, linear response range 10-3-3.93x10-6M) and the electrode with TCMA-LS ionophore and the same plasticizer (slope: 58.56 mV/concentration decade, linear response range 10-3- 2x10-6). Nearer values have been obtained for membrane with TCMA-LS ionophore, plasticized with TCF (slope: 58.89 mV/decade and linear response range 10-3-2.9x10-6 M).


Table 1. Influence of polymeric membrane composition on the performances of laurilsulfate sensible electrode.

The effect of different plasticizers in the sensing membrane on the performance of a surfactant ISE based on a PVC membrane with no added ion-exchanger was investigated. *o*nitrophenyl octyl ether (NPOE), o-nitrophenyldecyl ether (NPDE), *o*-nitrophenyl dodecyl ether (NPDOE) and *o*-nitrophenyl tetradecyl ether (NPTE) were used as plasticizers. Electrodes based on NPDE, NPDOE and NPTE produced better results than NPOEplasticized PVC membrane electrodes in terms of low detection limits. Electrodes based on NPDE, NPDOE and NPTE displayed a Nernstian slope in the concentration range of 10-6 to 10-2 M. NPOE plasticized PVC membrane electrodes displayed a Nernstian slope in the

production of detergents, in the industrial processes where anionic surfactants are used, in quality control of products containing added surfactants and in environment surveillance activities, especially monitoring water quality. In the last decades there have been created and improved numerous analytic methods for determination of anionic surfactants. Among these, there are the potentiometric methods based on potentiometric sensors (electrodes sensible to anionic surfactants). These are very attractive tools due to their good precision, relatively simple manufacturing, relatively low cost and their ability to determine the surfactants in the samples without previous separation steps (Mihali, 2006). The use of surfactant sensitive electrodes with plasticized polymeric membrane for the potentiometric determination of low concentrations of anionic surfactants has been described in several papers (Lizondo-Sabater et al, 2008; Matesic-Puac et. Al, 2005; Mihali et al., 2009; Nemma et

The selection of the most suitable plasticizer for the ion selective electrodes sensible to lauril sulfate anion based on ion-association complexes of quaternary ammonium cation and surfactant anion was made by testing the behavior of poly(vinyl chloride) membrane composition with two ionophores (Mihali et al., 2009) : cetyltrimethylammonium laurylsulfate (CTMA-LS) and tricaprylmethylammonium laurylsulfate (TCMA-LS). As plasticizers were used tricresylphosphate (TCF), ortho-nitrophenyloctylether (NPOE) and dioctylsebaccate (DOS). Comparing the electrodes prepared from the point of view of the linear response range and the slope (Table 1) we can notice that the best performances have been obtained with the CTMA-LS ionophore based electrode, plasticized with DOS (slope 59.39 mV/concentration decade, linear response range 10-3-3.93x10-6M) and the electrode with TCMA-LS ionophore and the same plasticizer (slope: 58.56 mV/concentration decade, linear response range 10-3- 2x10-6). Nearer values have been obtained for membrane with TCMA-LS ionophore, plasticized with TCF (slope: 58.89 mV/decade and linear response range 10-3-2.9x10-6 M). Ionophore / Plasticizer Membrane characteristics

mV/conc. decade Linear response range, M

DOS 59.39 10-3-3.93x10-6 TCF 58.19 10-3-4.2x10-6 NPOE 56.08 10-3-4.88x10-6

DOS 58.56 10-3-2x10-6 TCF 58.87 10-3-2.9x10-6 NPOE 55.07 10-3-3.5x10-6

Table 1. Influence of polymeric membrane composition on the performances of laurilsulfate

The effect of different plasticizers in the sensing membrane on the performance of a surfactant ISE based on a PVC membrane with no added ion-exchanger was investigated. *o*nitrophenyl octyl ether (NPOE), o-nitrophenyldecyl ether (NPDE), *o*-nitrophenyl dodecyl ether (NPDOE) and *o*-nitrophenyl tetradecyl ether (NPTE) were used as plasticizers. Electrodes based on NPDE, NPDOE and NPTE produced better results than NPOEplasticized PVC membrane electrodes in terms of low detection limits. Electrodes based on NPDE, NPDOE and NPTE displayed a Nernstian slope in the concentration range of 10-6 to 10-2 M. NPOE plasticized PVC membrane electrodes displayed a Nernstian slope in the

Slope,

al., 2009; Oprea et al. 2007 etc.)

Cetyltrimethylammonium laurylsulfate (CTMA-LS)

Tricaprylmethylammonium laurylsulfate (TCMA-LS)

sensible electrode.

concentration range of 10-5 to 10-2 M (Masadome et al., 2004). The three electrodes other than the NPOE - plasticized PVC membrane electrode showed a similar performance to that of the NPOE - plasticized PVC membrane electrode concerning low detection limits and slope sensitivity. The four electrodes examined in this study are excellently selective for the dodecyltrimethylammonium ion over inorganic anions, but interference from other cationic surfactants such as tetradecyltrimethylammonium ions is significant. With respect to slope sensitivity, selectivity, response time and pH effect, the four electrodes showed a similar performance. The use of NPOE derivatives as the more hydrophobic plasticizers in comparison to NPOE enhanced the performance of surfactant-selective PVC membrane electrodes with no added ion-exchanger with respect to low detection limits. On the other hand, the use of NPOE derivatives did not enhance the performance of surfactant - selective PVC membrane electrodes with respect to slope sensitivity, selectivity, response time or pH effect.

The cyclam derivative 1,4,8,11-tetra(*n*-octyl)-1,4,8,11-tetraazacyclotetradecane (L) has been used as carrier for the preparation of PVC-based membrane ion-selective electrodes for anionic surfactants (Lizondo-Sabater et al, 2008). Different membranes were prepared using L as ionophore, tetra *n*-octylammonium bromide (TOAB) as cationic additive and dibutyl phthalate (DBP) or *o*-nitrophenyl octyl ether (NPOE) as plasticizers. The final used electrode contained a membrane of the following composition: 56% DBP, 3.4% ionophore, 3.8% TOAB and 36.8% PVC. This electrode displays a Nernstian slope of −60.0 ± 0.9 mV/decade in a 2.0 × 10−3 to 7.9 × 10−6 mol dm−3 concentration range and a limit of detection of 4.0 × 10−6 mol dm−3. The electrode can be used for 144 days without showing significant changes in the value of slope or working range. The electrode shows a selective response to dodecyl sulfate (DS−) and a poor response to common inorganic cations and anions. The selective sequence found was DS− > ClO4− >HCO3− > SCN− >NO3 <sup>−</sup> ≈CH3COO<sup>−</sup> ≈I− >Cl− >Br− > IO3<sup>−</sup> ≈NO2<sup>−</sup> ≈SO32− > HPO4 <sup>2</sup>− >C2O42− >SO42−, i.e. basically following the Hoffmeister series except for the hydrophilic anion bicarbonate. Most of the potentiometric coefficients determined are relatively low indicating that common anions would not interfere in the DS− determination. A complete study of the response of the electrode to a family of surfactant was also carried out. The electrode showed a clear anionic response to DS− and to Na-LAS (sodium alkylbezenesulfonate) and a much poorer response to other anionic surfactants and to nonionic surfactants. Also the electrode shows certain non-linear cationic response in the presence of cationic and zwitterionic surfactants. The electrode was used for the determination of anionic surfactants in several mixtures, and the results obtained were compared to those found using a commercially available sensor.

#### **5. Selecting plasticizers for the construction of ion-selective electrodes used in pharmaceutical products analysis**

Potentiometry with ion-selective electrodes is one of the most useful analytical tools capable of measuring both inorganic and organic substances in pharmaceutical products (Kulapina & Barinova, 1997). At present, most works are devoted to establishing the factors providing desired modification of the properties of ion-selective membranes (Kulapina & Barinova, 1997). In this context, interesting results were reported on the effects of the ion association and the character of a plasticizing solvent on the selective properties of counter electrodes for the organic cations of drugs. It was suggested that the factor of ion association can be

Use of Plasticizers for Electrochemical Sensors 135

degree of substitution of the salt-forming nitrogen atom or if they differ in nature and (or) by the number of nonionic polar groups, capable of specifically interacting with the plasticizer, primarily, in the mechanism of the formation of hydrogen bonds. PAA cations, as a rule, possess sufficiently complex structures and, along with the salt-forming nitrogen atom, contain nonionic polar groups capable of specific solvation, which prevents the estimation of the "pure" effect of the plasticizer due to the difference in the degrees of substitution of the corresponding PAA cations. The selectivity coefficients of a Bu4N+-SE to the cations of primary, secondary, and tertiary amines strongly depend on the plasticizer nature and increases in the series NPOE < DBP < DNA < TEHP < DOPP. It was established that with an increase in the basicity of the plasticizer in the series NPOE < DNA < TEHP, the selectivity coefficients to quarternary ammonium cations naturally decrease, and the selectivity coefficients to the cations of secondary and, particularly, primary aliphatic amines increase.

The selectivity coefficients to the cations of triethyl and tributylammonium, and also to the cations of Dimedrol, Spasmolytin, Papaverin, Ketoconazole, and Vinpocetine slightly depend on the plasticizer nature. This results from the fact that, despite the strong difference in the structures of the above amines, their molecules, as the molecule of Ganglerone contain no groups capable of forming hydrogen bonds with basic plasticizers. On the contrary, the selectivity coefficients of the Ganglerone-SE to the cations of Bromhexine, Quinine, Trimecaine, Novocaine, and Pyridoxine significantly increase with an increase in the basicity of the plasticizer because of the presence of nonionic polar groups, –C(O)–NH–, – NH2, –OH capable of forming hydrogen bonds with basic plasticizers in their molecules. The strongest effect is observed on the pyridoxine cation, with three hydroxyl groups. The cations of Loperamide and Metoclopromide take exception to that general regularity due to the formation of intermolecular hydrogen bond. Thus, despite the presence of polar groups in their molecules capable of forming hydrogen bonds with Lewis bases the change of the basicity of the plasticizer slightly affects selectivity to the Loperamide cation while for the Metoclopromide cation, the effect is opposite to that expected: selectivity coefficient

A diclofenac-selective electrode for ionometric analysis was developed using polyvinyl chloride membranes plasticized with dioctylphthalate (DOP), dibutylphthalate (DBP), dinonylphthalate (DNP), dinonylsebacenate (DNS), tricresylphosphtate (TCP), in which the electrode-active substance was an ionic associate of diclofenac and neutral red. The electrode contained an ionic associate of diclofenac with neutral red and its response was linear over the diclofenac concentration range 5 x 10–5 to 5 x 10–2 M with an electrode function slope of (30.0 ± 1.1) - (44.0 ± 1.2) mV/pC, that differed according to the plasticizers that were used. This membrane electrode was used as a sensor for assaying diclofenac in

Procedures for determining ibuprofen with ion - selective electrodes are characterized by their rapidity, simplicity and low cost of the equipment, possibility of analyzing turbid and colored solutions, and acceptable selectivity and sensitivity (Nazarov et al., 2010). Membranes were prepared from polyvinil chloride (PVC), tetrahydrofuran (THF), and also

Currently, medicinal substances can be determined with a wide range of ion-selective electrodes of different types (biospecific, ion-exchange, neutral-carrier, etc.) with different

decreases from NPOE to TEHP.

pharmaceutical formulations (Kormosh et al., 2009).

a plasticizer dibutyl phthalate (DBP).

used to obtain electrodes with increased selectivity. An exemplary case study includes the proserine-selective electrode, in which substitution of the NPOE plasticizer, having high dielectric constant with the lower dielectric constant DBP lead to a significant increase in selectivity towards tertiary ammonium cations in the presence of amine and metallic cations. Researches on the dimedrol-selective electrode showed the same influence of the plasticizer's dielectrical properties on the electrode selectivity with respect to physiologically active amines. Using plasticizers with high basicity, as in the case of trihexylphosphate, leads to increases in selectivity with respect to cations containing electrophilic hydrogen atoms. The donor-acceptor interaction of the non-ionic polar groups of amines with the solvation active centers of the membranes macrocomponents is responsible for this high increase in selectivity.

Many pharmaceutical products belonging to different categories (such as analgesics and anesthetics, antibiotics, vitamins, neuroleptics, antiseptics, antiviral preparations, etc.) contain an amino functional group, in their structure, more or less substituted or a nitrogen atom included in a heterocyclic compound. They are called physiologically active amines (PPA) (Egorov et al, 2010). The ISEs selectivity towards the cations formed by the PPA can be controlled by changing the nature of the plasticizer, the ion exchanger or by introducing a neutral carrier capable of selectively complexing the analyte ions in the membranes. The most used method, and probably, the most effective method is the variation of the plasticizer's nature. The influence of the plasticizer's nature upon its selectivity towards PPAs was investigated (Egorov et al, 2010). Different PVC membrane compositions and ISEs sensible to PPAs were prepared and studied. Tetrakis (A-chlorophenyl potassium)borate (TCPB) and potassium tris(2,3,4-nonyloxy)benzene sulfonate were used as ion exchangers. In some membrane compositions a neutral carrier: dibenzo-18-crown-6 (DB-18-C-6) or a solvating additive: mono-decylresorcinol (MDR) was used. The influence of the plasticizer's basicity upon the selectivity of the ISEs was studied and therefor the following plasticizers were used: *ortho*-nitrophenyloctyl ether (NPOE), dibutyl phthalate (DBP), dinonyladipinate (DNA), tris(2-ethylhexyl) phosphate (TEHP), tris(ethylhexyl) phosphate 2 (TEHP), bis(2 ethylhexyl) adipate (DOA), dioctylphthalate (DOP), and bis (2-ethylhexyl) sebacate (DOS). The basicity increases as the series: NPOE<DBP<DNA<TEHP<DOPP. It was established that by increasing the plasticizer's basicity there is a pronounced increase in membrane selectivity towards PPA cations with a low substitution of the salt forming nitrogen atom. PPA atoms that contain non-ionic polar groups and can form hydrogen bonds with Lewis bases behave in the same way, but PPA cations forming intermolecular hydrogen bonds are an exception (Egorov et al, 2010; Kulapina & Barinova, 1997). The effect of the ion exchanger's nature upon PPA cation selectivity was stronger when plasticizers with low basicity were used. It was established that the selectivity of the membranes which were prepared using highly basic plasticizers does not depend on the ion exchanger's nature. The ISEs that contain the neutral carrier dibenzo-18-crown-6 (DB-18-C-6) have shown the best selectivity towards primary amines cations in comparison with secondary and tertiary, when low basicity plasticizers were used. It was found that the use of high basicity plasticizers leads to a significant increase of the ISE selectivity towards primary amines cations in comparison to quaternary amines.

The plasticizer nature can significantly affect the selectivity of an ISE reversible to amine cations only if at least one of two conditions is met: if the analyte and foreign ions differ in the

used to obtain electrodes with increased selectivity. An exemplary case study includes the proserine-selective electrode, in which substitution of the NPOE plasticizer, having high dielectric constant with the lower dielectric constant DBP lead to a significant increase in selectivity towards tertiary ammonium cations in the presence of amine and metallic cations. Researches on the dimedrol-selective electrode showed the same influence of the plasticizer's dielectrical properties on the electrode selectivity with respect to physiologically active amines. Using plasticizers with high basicity, as in the case of trihexylphosphate, leads to increases in selectivity with respect to cations containing electrophilic hydrogen atoms. The donor-acceptor interaction of the non-ionic polar groups of amines with the solvation active centers of the membranes macrocomponents is

Many pharmaceutical products belonging to different categories (such as analgesics and anesthetics, antibiotics, vitamins, neuroleptics, antiseptics, antiviral preparations, etc.) contain an amino functional group, in their structure, more or less substituted or a nitrogen atom included in a heterocyclic compound. They are called physiologically active amines (PPA) (Egorov et al, 2010). The ISEs selectivity towards the cations formed by the PPA can be controlled by changing the nature of the plasticizer, the ion exchanger or by introducing a neutral carrier capable of selectively complexing the analyte ions in the membranes. The most used method, and probably, the most effective method is the variation of the plasticizer's nature. The influence of the plasticizer's nature upon its selectivity towards PPAs was investigated (Egorov et al, 2010). Different PVC membrane compositions and ISEs sensible to PPAs were prepared and studied. Tetrakis (A-chlorophenyl potassium)borate (TCPB) and potassium tris(2,3,4-nonyloxy)benzene sulfonate were used as ion exchangers. In some membrane compositions a neutral carrier: dibenzo-18-crown-6 (DB-18-C-6) or a solvating additive: mono-decylresorcinol (MDR) was used. The influence of the plasticizer's basicity upon the selectivity of the ISEs was studied and therefor the following plasticizers were used: *ortho*-nitrophenyloctyl ether (NPOE), dibutyl phthalate (DBP), dinonyladipinate (DNA), tris(2-ethylhexyl) phosphate (TEHP), tris(ethylhexyl) phosphate 2 (TEHP), bis(2 ethylhexyl) adipate (DOA), dioctylphthalate (DOP), and bis (2-ethylhexyl) sebacate (DOS). The basicity increases as the series: NPOE<DBP<DNA<TEHP<DOPP. It was established that by increasing the plasticizer's basicity there is a pronounced increase in membrane selectivity towards PPA cations with a low substitution of the salt forming nitrogen atom. PPA atoms that contain non-ionic polar groups and can form hydrogen bonds with Lewis bases behave in the same way, but PPA cations forming intermolecular hydrogen bonds are an exception (Egorov et al, 2010; Kulapina & Barinova, 1997). The effect of the ion exchanger's nature upon PPA cation selectivity was stronger when plasticizers with low basicity were used. It was established that the selectivity of the membranes which were prepared using highly basic plasticizers does not depend on the ion exchanger's nature. The ISEs that contain the neutral carrier dibenzo-18-crown-6 (DB-18-C-6) have shown the best selectivity towards primary amines cations in comparison with secondary and tertiary, when low basicity plasticizers were used. It was found that the use of high basicity plasticizers leads to a significant increase of the ISE selectivity towards primary amines

The plasticizer nature can significantly affect the selectivity of an ISE reversible to amine cations only if at least one of two conditions is met: if the analyte and foreign ions differ in the

responsible for this high increase in selectivity.

cations in comparison to quaternary amines.

degree of substitution of the salt-forming nitrogen atom or if they differ in nature and (or) by the number of nonionic polar groups, capable of specifically interacting with the plasticizer, primarily, in the mechanism of the formation of hydrogen bonds. PAA cations, as a rule, possess sufficiently complex structures and, along with the salt-forming nitrogen atom, contain nonionic polar groups capable of specific solvation, which prevents the estimation of the "pure" effect of the plasticizer due to the difference in the degrees of substitution of the corresponding PAA cations. The selectivity coefficients of a Bu4N+-SE to the cations of primary, secondary, and tertiary amines strongly depend on the plasticizer nature and increases in the series NPOE < DBP < DNA < TEHP < DOPP. It was established that with an increase in the basicity of the plasticizer in the series NPOE < DNA < TEHP, the selectivity coefficients to quarternary ammonium cations naturally decrease, and the selectivity coefficients to the cations of secondary and, particularly, primary aliphatic amines increase.

The selectivity coefficients to the cations of triethyl and tributylammonium, and also to the cations of Dimedrol, Spasmolytin, Papaverin, Ketoconazole, and Vinpocetine slightly depend on the plasticizer nature. This results from the fact that, despite the strong difference in the structures of the above amines, their molecules, as the molecule of Ganglerone contain no groups capable of forming hydrogen bonds with basic plasticizers. On the contrary, the selectivity coefficients of the Ganglerone-SE to the cations of Bromhexine, Quinine, Trimecaine, Novocaine, and Pyridoxine significantly increase with an increase in the basicity of the plasticizer because of the presence of nonionic polar groups, –C(O)–NH–, – NH2, –OH capable of forming hydrogen bonds with basic plasticizers in their molecules. The strongest effect is observed on the pyridoxine cation, with three hydroxyl groups. The cations of Loperamide and Metoclopromide take exception to that general regularity due to the formation of intermolecular hydrogen bond. Thus, despite the presence of polar groups in their molecules capable of forming hydrogen bonds with Lewis bases the change of the basicity of the plasticizer slightly affects selectivity to the Loperamide cation while for the Metoclopromide cation, the effect is opposite to that expected: selectivity coefficient decreases from NPOE to TEHP.

A diclofenac-selective electrode for ionometric analysis was developed using polyvinyl chloride membranes plasticized with dioctylphthalate (DOP), dibutylphthalate (DBP), dinonylphthalate (DNP), dinonylsebacenate (DNS), tricresylphosphtate (TCP), in which the electrode-active substance was an ionic associate of diclofenac and neutral red. The electrode contained an ionic associate of diclofenac with neutral red and its response was linear over the diclofenac concentration range 5 x 10–5 to 5 x 10–2 M with an electrode function slope of (30.0 ± 1.1) - (44.0 ± 1.2) mV/pC, that differed according to the plasticizers that were used. This membrane electrode was used as a sensor for assaying diclofenac in pharmaceutical formulations (Kormosh et al., 2009).

Procedures for determining ibuprofen with ion - selective electrodes are characterized by their rapidity, simplicity and low cost of the equipment, possibility of analyzing turbid and colored solutions, and acceptable selectivity and sensitivity (Nazarov et al., 2010). Membranes were prepared from polyvinil chloride (PVC), tetrahydrofuran (THF), and also a plasticizer dibutyl phthalate (DBP).

Currently, medicinal substances can be determined with a wide range of ion-selective electrodes of different types (biospecific, ion-exchange, neutral-carrier, etc.) with different

Use of Plasticizers for Electrochemical Sensors 137

containing tetraoctylammonium chloride (TOA–Cl) in the membrane, similar potentiometric responses were obtained. It can be concluded that the chemical structure, lipophilicity and polarity of the plasticizers did not exert any considerable influence on the parameters of calibration graphs, either with tetraoctylammonium- or methyltrioctylammonium anion exchangers. The type of quaternary ammonium salt and plasticizer affects the selectivity coefficient of the naproxen electrodes. However, the polarity of plasticizers was not significant, resulting in the lowest selectivity towards lipophilic ions for the more hydrophilic salts, and the lower concentration of cationic sites in the membrane in

An ion selective electrode for a vasoactive drug, Udenafil was developed (Han et al., 2010). Undafill is (5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulphonyl)phenyl]-1 methyl-3-propyl-1,6-dihydro-7-H-pyrazolo(4,3-d)pyrimidin-7-one). The electrode was based on ion pairs of Udenafil with different anions: tetrakis-*m*-chlorophenyl borate (TmCIPB), tetraphenylborate (TPB) and phosphomolybdic anion (PMA). The slopes of electromagnetic field responses and the response range of a solid contact electrode based on Udenafil - TmCIPB ion pair with those based on Udenafil - PMA and Udenafil - TPB ion pairs were compared, and showed that the response slopes were influenced by plasticizers. When electrodes with 6 different plasticizers based on Udenafi - TmCIPB were compared, as the dielectric constant of PVC plasticizer increased, so was the response slope at the same time. Various plasticizers (DOS, NPOE, DOP, TEHP, DOA, DBP) were tested for best response (Han et al., 2010). An anionic additive KTpCIPB (potassium tetrakis(4-chlorophenyl) borate) was also used. The composition of this solid contact electrode based on Udenafil - TmCIPB ionophore was Udenafil - TmCIPB ion pair 0.050 : PVC 0.190 : NPOE 0.350 : KTpCIPB 0.001 (potassium tetrakis(4-chlorophenyl) borate) as additive. However, it appeared that remaining two electrodes compared to the electrode based on Udenafil - TmCIPB ionophore had decreased Nernstian slopes and reduced response ranges (Han et al., 2010). However, as dielectric constant increased, so was the Nernstian slope. The solid contact electrodes based on Udenafil - TmCIPB which used NPOE plasticizer (dielectric constant of about 24) showed the best Nernstian slope, and those using another plasticizer as DBP (6.4), DOP (5.1), DOS (4.6), DOA (about 4.0), TEHP (about 4.0) had lower Nernstian slope and narrower dynamic range. According to the increase in the dielectric constant of plasticizers, the Nernstian slope of solid contact electrode increases. The tendency of this type of electrodes is that the dielectric constant of plasticizer and liphophilicity of KTpCIPB in PVC layer reduces the membrane resistance by reducing the activation barrier at the PVC outer surface sample solution interface and increases the mobility of Udenafil between the PVC outer surface and the sample solution. So, solid contact electrodes based on Udenafil - TmCIPB plasticized with NPOE containing KTpClPB showed better recovery precision, response time and less standard deviation than solid

consequence of the exchanger leaving the membrane.

contact electrodes with other plasticizers or with no KTpCIPB at all.

(Kumar et al., 2007).

A novel electrochemical sensor has been developed for the determination of nimesulide (NIM). The sensor is based on the NIM- molybdophosphoric acid (MPA) as the electroactive material in PVC matrix in presence of bis(2-ethyl hexyl) phthalate (BEP) as a plasticizer

Five different plasticizers were employed to study their effect on the electrochemical behaviour of the electrochemical sensor for nimesulfide: bis(2-ethyl hexyl) phthalate (BEP),

electroanalytical characteristics (Kulapina & Barinova, 2001).. Tetrahydrofuran was used as the solvent for polyvinyl chloride; as solvent–plasticizers, dibutyl phthalate, dioctyl phthalate, and tributyl phosphate of analytical grade and *o*-nitrophenyloctyl ether were used. Solvents were purified by distillation; refractive indices were measured on a laboratory refractometer. It is known that electroanalytical properties of plasticized membrane electrodes are determined by the properties of both the ion exchanger and the solvent plasticizer. Therefore, electrode and transport properties of membranes were studied based on the above ion pairs. Transport properties of membranes were studied by the electrical conduction method and under applied potential conditions. The introduction of the compound of the medicinal substance and tetraphenyl borate into a membrane increases its conductivity (0.4 - 3.1 µS at *C*ionophore = 0.001 – 0.1 mol/kg of dibutyl phthalate) compared to the background conductivity (0.25 µS). Specific conductivity of membranes is nearly unaffected by the nature of the counterion; this indicates that mobilities of cations of medicinal substances in the membrane phase are close to each other. The apparent dissociation constant of the novocaine tetraphenyl borate ion pair in the membrane phase was estimated from stationary values of specific conductivity at 1.6 x 10-2.

From the total of the obtained data, it follows that membranes under study (based on medicinal substance–tetraphenyl borate ion pairs) belong to liquid membranes with a dissociated ion exchanger, whose selectivity is controlled predominantly by the solvating ability of the solvent–plasticizer with respect to the analyte ion (Kulapina & Barinova, 2001). This fact was confirmed by complex studies on revealing the influence of the nature and concentration of the ionophore, the nature of the solvent plasticizer (dibutyl phthalate, dioctyl phthalate, tributyl phosphate, or *orto*-nitrophenyloctyl ether), and the polyvinyl chloride–plasticizer ratio in the membrane on the selective properties of electrodes. The comparative analysis of the electrochemical behavior of membranes was based on the results of studying the main operation parameters of ion-selective electrodes based on some membranes. It was demonstrated that electrodes with blank membranes containing polyvinyl chloride and the above solvent plasticizers exhibit the cationic function in solutions of physiologically active amines, and in this case, the linearity range and the slope of electrode functions depend on the nature of the plasticizer. Membranes based on tributyl phosphate lose elasticity after operation for two weeks because of a significant solubility of tributyl phosphate in water. Electrodes based on dibutyl phthalate and dioctyl phthalate exhibit the best electrode characteristics. The introduction of an ionophore significantly improves electrochemical and operating characteristics of electrodes. Similarly to blank membranes, electrodes based on dibutyl phthalate (as well as dioctyl phthalate) exhibit the best characteristics, i.e., the selectivity of ion-exchange membranes is determined by the solvating ability of the plasticizer. The nature of the medicinal substance incorporated into the ionophore only insignificantly affects the linearity range of electrode functions.The experimental data on varying the composition of membranes demonstrated that membranes based of dibutyl phthalate (as well as dioctyl phthalate) with a polyvinyl chloride– plasticizer ratio of 1 : 3 and the concentration of the ionophore 0.01 mol/kg of plasticizer exhibit the optimal characteristics.

The influence of the polarity and chemical structure of the plasticizer on the potentiometric response of the electrodes was investigated. Comparing the results, the best electrodes, containing methyltrioctylammonium chloride (MTOA–Cl) in the membrane, are appropriately plasticized with DBP, NPOE and TEHP (Lenik et al., 2008). For electrodes

electroanalytical characteristics (Kulapina & Barinova, 2001).. Tetrahydrofuran was used as the solvent for polyvinyl chloride; as solvent–plasticizers, dibutyl phthalate, dioctyl phthalate, and tributyl phosphate of analytical grade and *o*-nitrophenyloctyl ether were used. Solvents were purified by distillation; refractive indices were measured on a laboratory refractometer. It is known that electroanalytical properties of plasticized membrane electrodes are determined by the properties of both the ion exchanger and the solvent plasticizer. Therefore, electrode and transport properties of membranes were studied based on the above ion pairs. Transport properties of membranes were studied by the electrical conduction method and under applied potential conditions. The introduction of the compound of the medicinal substance and tetraphenyl borate into a membrane increases its conductivity (0.4 - 3.1 µS at *C*ionophore = 0.001 – 0.1 mol/kg of dibutyl phthalate) compared to the background conductivity (0.25 µS). Specific conductivity of membranes is nearly unaffected by the nature of the counterion; this indicates that mobilities of cations of medicinal substances in the membrane phase are close to each other. The apparent dissociation constant of the novocaine tetraphenyl borate ion pair in the membrane phase

From the total of the obtained data, it follows that membranes under study (based on medicinal substance–tetraphenyl borate ion pairs) belong to liquid membranes with a dissociated ion exchanger, whose selectivity is controlled predominantly by the solvating ability of the solvent–plasticizer with respect to the analyte ion (Kulapina & Barinova, 2001). This fact was confirmed by complex studies on revealing the influence of the nature and concentration of the ionophore, the nature of the solvent plasticizer (dibutyl phthalate, dioctyl phthalate, tributyl phosphate, or *orto*-nitrophenyloctyl ether), and the polyvinyl chloride–plasticizer ratio in the membrane on the selective properties of electrodes. The comparative analysis of the electrochemical behavior of membranes was based on the results of studying the main operation parameters of ion-selective electrodes based on some membranes. It was demonstrated that electrodes with blank membranes containing polyvinyl chloride and the above solvent plasticizers exhibit the cationic function in solutions of physiologically active amines, and in this case, the linearity range and the slope of electrode functions depend on the nature of the plasticizer. Membranes based on tributyl phosphate lose elasticity after operation for two weeks because of a significant solubility of tributyl phosphate in water. Electrodes based on dibutyl phthalate and dioctyl phthalate exhibit the best electrode characteristics. The introduction of an ionophore significantly improves electrochemical and operating characteristics of electrodes. Similarly to blank membranes, electrodes based on dibutyl phthalate (as well as dioctyl phthalate) exhibit the best characteristics, i.e., the selectivity of ion-exchange membranes is determined by the solvating ability of the plasticizer. The nature of the medicinal substance incorporated into the ionophore only insignificantly affects the linearity range of electrode functions.The experimental data on varying the composition of membranes demonstrated that membranes based of dibutyl phthalate (as well as dioctyl phthalate) with a polyvinyl chloride– plasticizer ratio of 1 : 3 and the concentration of the ionophore 0.01 mol/kg of plasticizer

The influence of the polarity and chemical structure of the plasticizer on the potentiometric response of the electrodes was investigated. Comparing the results, the best electrodes, containing methyltrioctylammonium chloride (MTOA–Cl) in the membrane, are appropriately plasticized with DBP, NPOE and TEHP (Lenik et al., 2008). For electrodes

was estimated from stationary values of specific conductivity at 1.6 x 10-2.

exhibit the optimal characteristics.

containing tetraoctylammonium chloride (TOA–Cl) in the membrane, similar potentiometric responses were obtained. It can be concluded that the chemical structure, lipophilicity and polarity of the plasticizers did not exert any considerable influence on the parameters of calibration graphs, either with tetraoctylammonium- or methyltrioctylammonium anion exchangers. The type of quaternary ammonium salt and plasticizer affects the selectivity coefficient of the naproxen electrodes. However, the polarity of plasticizers was not significant, resulting in the lowest selectivity towards lipophilic ions for the more hydrophilic salts, and the lower concentration of cationic sites in the membrane in consequence of the exchanger leaving the membrane.

An ion selective electrode for a vasoactive drug, Udenafil was developed (Han et al., 2010). Undafill is (5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulphonyl)phenyl]-1 methyl-3-propyl-1,6-dihydro-7-H-pyrazolo(4,3-d)pyrimidin-7-one). The electrode was based on ion pairs of Udenafil with different anions: tetrakis-*m*-chlorophenyl borate (TmCIPB), tetraphenylborate (TPB) and phosphomolybdic anion (PMA). The slopes of electromagnetic field responses and the response range of a solid contact electrode based on Udenafil - TmCIPB ion pair with those based on Udenafil - PMA and Udenafil - TPB ion pairs were compared, and showed that the response slopes were influenced by plasticizers. When electrodes with 6 different plasticizers based on Udenafi - TmCIPB were compared, as the dielectric constant of PVC plasticizer increased, so was the response slope at the same time. Various plasticizers (DOS, NPOE, DOP, TEHP, DOA, DBP) were tested for best response (Han et al., 2010). An anionic additive KTpCIPB (potassium tetrakis(4-chlorophenyl) borate) was also used. The composition of this solid contact electrode based on Udenafil - TmCIPB ionophore was Udenafil - TmCIPB ion pair 0.050 : PVC 0.190 : NPOE 0.350 : KTpCIPB 0.001 (potassium tetrakis(4-chlorophenyl) borate) as additive. However, it appeared that remaining two electrodes compared to the electrode based on Udenafil - TmCIPB ionophore had decreased Nernstian slopes and reduced response ranges (Han et al., 2010). However, as dielectric constant increased, so was the Nernstian slope. The solid contact electrodes based on Udenafil - TmCIPB which used NPOE plasticizer (dielectric constant of about 24) showed the best Nernstian slope, and those using another plasticizer as DBP (6.4), DOP (5.1), DOS (4.6), DOA (about 4.0), TEHP (about 4.0) had lower Nernstian slope and narrower dynamic range. According to the increase in the dielectric constant of plasticizers, the Nernstian slope of solid contact electrode increases. The tendency of this type of electrodes is that the dielectric constant of plasticizer and liphophilicity of KTpCIPB in PVC layer reduces the membrane resistance by reducing the activation barrier at the PVC outer surface sample solution interface and increases the mobility of Udenafil between the PVC outer surface and the sample solution. So, solid contact electrodes based on Udenafil - TmCIPB plasticized with NPOE containing KTpClPB showed better recovery precision, response time and less standard deviation than solid contact electrodes with other plasticizers or with no KTpCIPB at all.

A novel electrochemical sensor has been developed for the determination of nimesulide (NIM). The sensor is based on the NIM- molybdophosphoric acid (MPA) as the electroactive material in PVC matrix in presence of bis(2-ethyl hexyl) phthalate (BEP) as a plasticizer (Kumar et al., 2007).

Five different plasticizers were employed to study their effect on the electrochemical behaviour of the electrochemical sensor for nimesulfide: bis(2-ethyl hexyl) phthalate (BEP),

Use of Plasticizers for Electrochemical Sensors 139

We presented here the importance and proper use of plasticizers in the preparation of membranes for ion-selective electrodes. The nature of the plasticizer influences key performance indicators of the ion-selective membrane electrodes such as slope, the domain of linear response and the selectivity. A plasticizer for the membrane preparation has to be compatible with the polymer and also with the electrodic component (ionophore), and have a high lipophilicity and low solubility in aqueous solution. The selection of the best plasticizer for the development of a polymeric membrane specific to a certain ion usually involves experimental tests in order to find the plasticizer and the ionophore with which the best response characteristics of the ion -selective electrodes are obtained. Several examples of selecting the best suited plasticizer for the design of selective electrodes sensitive to

Baek, J.; Kim, J-S.; Paeng, I. K. & Paeng, K-J. (2008). The Composition Dependence Selectivity

Egorov, V. V.; Astapovich, R. I.; Bolotin, A. A.; Vysotskii, D. L.; Nazarov, V. A.; Matulis, V.

El-Nemmaa, EM., Badawib, BN., Saad S.M. Hassan, SSM. ( 2009). Cobalt phthalocyanine as

Evsevleeva, L. G.; Bykova, L. M. & Badenikov V. Ya. (2005). Aluminum-Selective Electrode.

Han, W. S.; Lee Y. H.; Jung K. J.; Ly S. Y.; Hong T. K. & Kim M. H. (2008). Potassium Ion-

Han, W-S.; Kim, J-K.; Chung, K-C.; Hong, J-Y.; Hong, J-K.; Kim, J-H. & Hong, T-K. (2010).

Kormosh, Zh. A.; Hunka, I. P. & Bazel, Y. R. (2009). An Ion-Selective Sensor for Assay of Diclofenac in Medicines. *Pharmaceutical Chemistry Journal*, Vol. 43, No. 7, pp. 54-56 Kulapina, E. G. & Barinova, O. Y. (1997). Structures of Chemical Compounds, Methods of

Kulapina, E. G. & Barinova, O. V. (2001). Ion-Selective Electrodes for the Determination of

Kumar, K. G.; Augustine, P. & John, S. (2007), A Novel Potentiometric Sensor for the Determination of Nimesulide. *Portugaliae Electrochimica Acta*, No. 25, pp. 375-381

*Journal of Analytical Chemistry*, Vol. 60, No. 9, pp. 866-867

*Chemistry,* Vol. 65, No. 10, pp. 1035-1040, ISSN 1061-9348

*Pharmaceutical Chemistry Journal,* Vol. 11, No. 12, pp. 40-45

*Bulletin of the Korean Chemical Society,* Vol. 29, No. 1, pp. 165-167

Changes by Plasticizer at the Cation Sensors Based on Tetracycline Antibiotics.

E. & Ivashkevich, O. A. (2010). The Influence of the Plasticizer Nature on the Selectivity of Ion-Selective Electrodes to Physiologically Active Amine Cations: Regularities and Abnormalities. *Journal of Analytical Chemistry*, Vol. 65, No. 4, pp.

a novel molecular recognition reagent for batch and flow injection potentiometric and spectrophotometric determination of anionic surfactants. *Talanta*, Vol. 78 pp.

Selective Polyaniline Solid-Contact Electrodes Based on 4',4"(5")-Di-tert butyldibenzo-18-crown-6-ether Ionophore. *Journal of Analytical Chemistry,* Vol. 63,

Poly(aniline) Solid Contact Ion Selective Electrode for Udenafil. *Journal of Analytical* 

Analysis and Process Control - Ion-Selective Electrodes in Drug Analysis.

Nitrogen-Containing Medicinal Substances. *Journal of Analytical Chemistry*, Vol. 56,

inorganic and organic ions have been presented in a detailed manner.

**6. Conclusions** 

**7. References** 

404-413, ISSN 1061-9348

No. 10, pp. 987-993, ISSN 1061-9348

723-729.

No. 5, pp. 457-460

bis(2-ethy hexyl) sebacate (BES), di-buthyl sebacate (DBS), bis(2-ethyl hexyl) adipate (BEA), di-n-butyl phthalate (DBP). Generally, the use of plasticizers improve certain characteristics of the membranes, and in some cases, the slopes get affected adversely. Here, the slopes in the case of the BES, DBS and DBP are super-Nernstian and BEA is sub-Nernstian. It was found that BEP gave a near Nernstian slope. The potentiometric response characteristics of the NIM sensor based on the use of NIM – MPA (ion association nimesulfide molybdophosphoric acid). ion pair as the electroactive material and BEP as a plasticizer in a PVC matrix were examined (Kumar et al., 2007). The slope was 55.6 mV/decade over the concentration range 1.0×10-6 – 1.0×10-2 M of NIM.


The most used plasticizers in the construction of ion selective electrodes are summarized in Table 2.

Table 2. Plasticizer used in some ion selective electrodes with polymeric membrane.

#### **6. Conclusions**

138 Recent Advances in Plasticizers

bis(2-ethy hexyl) sebacate (BES), di-buthyl sebacate (DBS), bis(2-ethyl hexyl) adipate (BEA), di-n-butyl phthalate (DBP). Generally, the use of plasticizers improve certain characteristics of the membranes, and in some cases, the slopes get affected adversely. Here, the slopes in the case of the BES, DBS and DBP are super-Nernstian and BEA is sub-Nernstian. It was found that BEP gave a near Nernstian slope. The potentiometric response characteristics of the NIM sensor based on the use of NIM – MPA (ion association nimesulfide molybdophosphoric acid). ion pair as the electroactive material and BEP as a plasticizer in a PVC matrix were examined (Kumar et al., 2007). The slope was 55.6 mV/decade over the

The most used plasticizers in the construction of ion selective electrodes are summarized in

Performances of the sensor

Slope of 58mV/pC, detection limit (DL) of 10–5.8 M

Slope of 20.7 mV/pC, Linear response range: 10-5-1 M

Slope of 58.56 mV/pC, Linear response range: 2x10-6-10-3 M

> Dynamic range of 10-6-10-1 M, DL: 10-7

Slope of 44 mV/pC, Linear response range: 5x10-5 -5x10-2 M

Slope of 60.3 mV/pC, Linear response range: 10-5.7 -10-2 M

Ref.

(Han et al., 2008)

(Evsevleeva et al., 2005)

(Mihali et al., 2009)

(Trebbe et al., 2001)

(Kormosh et al., 2009)

> (Han et al., 2010).

Ion toward which the membrane is / Electrodic component

K/4',4''(5'')-ditertbutyldibenzo-18-crown-6 ether

Lauryl-sulfate/ tricaprylmethylammonium laurylsulfate

Ca/Calciumionophore I (ETH 1001)

Diclofenac sodium/ion associate of diclofenac and neutral red

> Udenafil /Udenafil-TmClPB

Table 2. Plasticizer used in some ion selective electrodes with polymeric membrane.

PVC Al /aluminon

concentration range 1.0×10-6 – 1.0×10-2 M of NIM.

Polymer

PVC, polyaniline

PVC

Polyurethane

PVC

Table 2.

Name of the plasticizer used in the preparation of the polymeric membrane, their proportion (wt% )

bis(2-ethylhexyl) adipate (DOA), 64,2 %

dibutyl phthalate (DBP) as plasticizer, 33 %.

bis(2-ethylhexyl) sebacate (DOS), 66%

orto-Nitrophenyl octyl ether (NPOE), 63 %

dicotylphtalate

orto-Nitrophenyl octyl ether (NPOE), 59%

(DOP), 66% PVC

We presented here the importance and proper use of plasticizers in the preparation of membranes for ion-selective electrodes. The nature of the plasticizer influences key performance indicators of the ion-selective membrane electrodes such as slope, the domain of linear response and the selectivity. A plasticizer for the membrane preparation has to be compatible with the polymer and also with the electrodic component (ionophore), and have a high lipophilicity and low solubility in aqueous solution. The selection of the best plasticizer for the development of a polymeric membrane specific to a certain ion usually involves experimental tests in order to find the plasticizer and the ionophore with which the best response characteristics of the ion -selective electrodes are obtained. Several examples of selecting the best suited plasticizer for the design of selective electrodes sensitive to inorganic and organic ions have been presented in a detailed manner.
