Content uploaded by Christine Maged El Maraghy
Author content
All content in this area was uploaded by Christine Maged El Maraghy on Mar 17, 2016
Content may be subject to copyright.
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478
Full Paper
Ion Selective Membrane Electrodes for Determination of
Citalopram Hydrobromide in Drug Product and in
Presence of Its Degradation Products
Marianne Nebsen,1,2 Christine M. El-Maraghy,3,* Hesham Salem4 and Sawsan M.
Amer1
1Analytical Chemistry department, Faculty of Pharmacy, Cairo University, Kasr-El Aini
Street, 11562Cairo, Egypt
2Pharmaceutical Analytical Chemistry department, Faculty of Pharmacy & Drug
Technology, Heliopolis University, 3 Cairo Belbeis desert road, 2834El- Horria, Cairo,
Egypt
3Analytical Chemistry department, Faculty of Pharmacy, October University for Modern
Sciences and Arts (MSA), 11787 6th October city, Egypt
4Pharmaceutical Analytical Chemistry department, Faculty of Pharmacy, Deraya University,
Minia, Egypt
* Corresponding Author, Tel.: +201223553561
E-Mail: christine_elmaraghy@hotmail.com
Received: 21 May 2015 / Accepted with minor revision: 12 August 2015 /
Published online: 31 August 2015
Abstract- This paper presents a comparative study between three sensors developed to
determine Citalopram Hydrobromide (CT) in the presence of its alkaline hydrolysis and
oxidation induced degradation products using different ion association complexes. Sensor 1
was fabricated using phosphomolybdic acid, Sensor 2 used phosphotungestic acid and sensor
3 used the sodium tetraphenyl borate. Linear responses of CT were obtained within the
concentration ranges of 1×10−6 to 1×10−2 mol L-1 for sensor 1 and 2 and 1×10−5 to 1×10−2
mol L-1 for sensor 3 over the pH range of 3.0–6.0. The selectivity coefficients of the
developed sensors indicated excellent selectivity for CT. The proposed sensors displayed
useful analytical characteristics for the determination of CT in bulk powder, pharmaceutical
formulation, and in the presence of its degradation products and thus could be used for
stability-indicating methods. The method was validated according to ICH guidelines.
Analytical &
Bioanalytical
Electrochemistry
2015 by CEE
www.abechem.com
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 467
O
O
N
N
C
CH
H
3
3
C
CH
H
3
3
F
F
N
NC
C
H
HB
Br
r
-
-
Statistical comparison between the results from the proposed method and the results from the
reference HPLC method showed no significant difference regarding accuracy and precision.
Keywords- Citalopram Hydrobromide, Ion selective electrode, Degradation products, Cation
exchanger, PVC
1. INTRODUCTION
Citalopram (CT) (Fig. 1), 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-5-phthalan
carbonitrile, is an antidepressant drug used to treat depression associated with mood
disorders. CT belongs to a class of drugs known as selective serotonin reuptake inhibitors
(SSRIs). It affects the neurotransmitters, the chemical transmitters within the brain. It works
by preventing the uptake of serotonin by nerve cells after it has been released. Such uptake is
an important mechanism for removing released neurotransmitters and terminating their
actions on adjacent nerves. The reduced uptake caused by CT results in stimulation of the
nerve cells by the free serotonin in the brain [1].
Fig. 1. Chemical structure of Citalopram Hydrobromide
Several methods have been reported for the determination of CT including
spectrophotometry [2-5], capillary electrophoresis [6-8], gas chromatography [9], thin layer
chromatography [10] and high performance liquid chromatography [11-13].
However, these reported methods involve long procedures, sample pretreatment,
utilization of expensive instruments and they are inapplicable to colored and turbid solutions.
On the contrary, electrochemistry offers instrumental simplicity, portability and moderate
cost [14].The ion-selective electrodes (ISEs) application in pharmaceutical analysis have
increased due to the advantages of portability, limited sample pretreatment, low energy
consumption, rapidity, and adaptability to small sample volumes [15,16] . Furthermore, they
show rapid response to changes in concentration and are tolerant to small changes in pH.
Various reports have been published which highlight the important contribution of ion
selective sensors for quantification of drugs [17,18]. Thus, the development of reliable ISEs
offering these advantages for the determination of CT in presence of its alkaline hydrolysis
and oxidation induced degradation products is desirable, especially given that the literature
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 468
reveal only two papers for determination of CT using ion exchanger [19,20]. The first paper
developed citalopram-tetraphenyl borate ion-pair PVC membrane with sensitivity of (1×10−5
to 1×10−2 mol L-1) which is less than our developed sensors 1 and 2 and the second paper
developed screen-printed ISEs using homemade carbon ink with shorter life time. Both
previous published sensors are not stability–indicating methods as our sensors.
The aim of this work was to develop simple easily prepared ion selective electrodes for
rapid, reproducible, selective, sensitive, accurate and low-cost estimation of the cationic drug
CT in the presence of its degradation products, in its pure form and pharmaceutical
formulation without the need of preliminary extraction or separation steps.
2. EXPERIMENTAL
2.1. Apparatus
A Jenway digital ion analyzer model 3330 (Essex, UK) with Ag/AgCl double junction
reference electrode no. 924017-LO3-Q11C was used for potential measurements. A pH glass
electrode Jenway (Essex, UK) no. 924005-BO3-Q11C was used for pH adjustment.
2.2. Materials
2.2.1. Reference sample
A pure sample of Citalopram hydrobromide (CT) (purity 99.87%) was supplied by
SEDICO Company for pharmaceuticals and chemical industries (Cairo, Egypt).
2.2.2. Pharmaceutical formulation
Citalo® tablets. Each tablet is claimed to contain 20 mg of CT. they were manufactured
by Delta Pharma Company, Cairo, Egypt.
2.3. Chemicals and reagents
All chemicals and reagents used were of analytical grade and water was bi-distilled.
Dioctyl phthalate (DOP), dibutyl phthalate (DBP) were obtained from Sigma (St. Louis,
USA), sodium tetraphenylborate (NaTPB), phosphotungestic acid (PTA), phosphomolybdic
acid (PMA), tetrahydrofuran (THF), poly vinyl chloride (PVC) were obtained from BDH
(Poole, England). Orthophosphoric acid for adjusting the phosphate buffer to pH 5.3 (Riedel-
dehaen, Sigma-Aldrich, Germany). Potassium chloride, sodium hydroxide pellets,
hydrochloric acid 30-34%, hydrogen peroxide 30% , Potassium dihydrogen orthophosphate
(ADWIC, Egypt).
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 469
2.4. Standard solutions
2.4.1. CT stock standard solution (1×10-2 mol L−1)
The solution was prepared by transferring 0.405 gm of pure CT into a 100-mL volumetric
fask, which was dissolved in sufficient amount of phosphate buffer pH ( 5.3), and then the
volume was brought up to the mark with the same solvent.
2.4.2. CT working standard solutions (1×10-7-1×10-2 mol L−1)
CT working solutions were freshly prepared by serial dilutions from the CT stock
solution using phosphate buffer (pH 5.3) as a solvent.
2.5. Procedures
2.5.1. Preparation of the PVC master membrane sensors
A 50 mL aliquot of 1.0×10-2 mol L−1 aqueous CT solution was mixed with 50 mL of
1.0×10-2 mol L−1 aqueous solution of phosphomolybdic acid (PMA) for sensor 1,
phosphotungestic acid (PTA) for sensor 2 and sodium tetraphenyl borate (NaTPB) for sensor
3 and continuously stirred. Each ion pair complex was precipitated, filtered, washed
thoroughly with bi-distilled water, dried at room temperature and ground to a fine powder. A
10 mg portion of CT ion pair was mixed with 0.35 mL of DOP plasticizer and 190 mg of
PVC powder and dissolved in 6 mL of THF. The solution was poured into Petri dishes (5 cm
diameter). The petri dishes were covered with whatman NO.3 filter paper and left to stand
overnight to allow solvent evaporation at room temperature. Master membranes with
thickness of 0.1 mm were obtained and used for the construction of the sensors.
2.5.2. Preparation of the electrodes assemblies
From each prepared master membrane, a disk (≈1.6 cm diameter) was cut using a cork
borer and pasted using THF to an interchangeable PVC tip that was clipped into the end of
the glassy electrode body. Equal volumes of 10-2 mol L−1 CT and 10-2 mol L−1 KCl (prepared
in phosphate buffer, pH 5.3) were mixed and this solution was used as internal solution for
electrodes. Ag/AgCl wire (1mm diameter) was immersed in the internal reference solution as
an internal reference electrode. The electrodes were conditioned by soaking in 1×10-2 mol L−1
stock standard CT solution for 24 hours and were stored in the same solution when not in use.
The electrochemical cell for potential measurements was: Ag/AgCl (internal reference
electrode) / 1.0×10-2 mol L−1 CT solution, 1.0×10-2 mol L−1 KCl (internal reference solution)
// PVC membrane//test solution // Ag/AgCl double junction reference electrode.
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 470
2.5.3. Sensors calibration
Each sensor was separately conjugated with a double junction Ag/AgCl reference
electrode, calibrated by being immersed in drug solutions covering the concentration range of
(1×10-7-1×10-2 mol L−1) and allowed to equilibrate while stirring until achieving a constant
reading of the potentiometer. The electrodes were washed with phosphate buffer, pH 5.3
between measurements. The developed potentials were plotted versus negative logarithmic
concentration of CT standard solutions. The regression equations of the obtained calibration
plots were used for subsequent measurements of unknown samples of CT.
2.5.4. Preparation of degradation products
2.5.4.1. Alkaline degradation
CT alkaline degradation product was obtained by heating 0.02 gm CT with 20 mL 5.0 M
sodium hydroxide at 80°C in oven for three hours. The resulting solution was neutralized
with HCl, transferred into 50-mL volumetric flask and completed to the mark with bi-distilled
water to obtain concentration of 1×10-3 mol L−1and tested for complete degradation by the
thin layer chromatography (TLC) technique using ethyl acetate: formic acid: acetic acid:
methanol in a ratio (12:1:1:1, v/v/v/v) as a mobile phase and detecting the spots at 254 nm.
2.5.4.2. Oxidative degradation
CT oxidative degradation product was obtained by heating 0.02 gm CT with 20 mL 30%
H2O2 at 70 °C in oven for five hours. The resulting solution transferred into 50-mL
volumetric flask and completed to the mark with bi-distilled water to obtain concentration of
1×10-3 mol L−1and tested for complete degradation with the same mobile phase system of
TLC.
(a) (b)
Fig. 2. Structures of alkaline (a) and oxidative (b) degradation products of Citalopram
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 471
2.5.5. Determination of CT in its pharmaceutical formulation
The contents of 10 tablets were accurately weighed, their average weight was calculated,
and then finely powdered. An amount equivalent to 0.02 gm CT was accurately weighed and
transferred into 50-mL beaker. Thirty mL of bi-distilled water were added and the solution
was sonicated for 30 min. Then filtered into 50-mL volumetric flask, and the volume was
completed with bi-distilled water to obtain concentration of 1×10-3 mol L−1. The
potentiometric measurement was performed using the proposed sensors in conjunction with
the Ag/AgCl reference electrode, the resulting potential was recorded, and the respective
concentration was calculated from the corresponding regression equations.
2.5.6. Determination of CT in the presence of its degradation products
Aliquots of standard drug solution (10−3 mol L−1) were mixed with its alkaline and
oxidative degraded sample (10−3 mol L−1) in different ratios. The emf values of these
laboratory-prepared mixtures were recorded and the concentration of the drug was calculated
from the corresponding regression equations.
2.5.7. Estimation of the slope, response time and operative life of the proposed sensors
The slope, response time and operative life of the three proposed sensors were evaluated
according to the IUPAC recommendations [21].
2.5.8. Effect of pH
The effect of pH on the potential values of the three sensors was studied over pH ranges
of 2-12. This was manipulated by adding diluted aliquots of 0.1 mol L−1 hydrochloric acid
and 0.1 mol L−1 sodium hydroxide solutions to 1×10-3 mol L-1 solution of CT solution. The
potential obtained at each pH value was recorded.
2.5.9. Effect of interfering substances on the electrode selectivity
The potential response of the three proposed sensors in the presence of interfering
substances was studied, and the potentiometric selectivity coefficient .
was calculated
to estimate the degree to which a foreign substance would interfere with the response of the
electrode to their primary ion. The selectivity coefficients were calculated by separate
solution method (SSM) [22] from the rearranged Nicolsky Eisenman equation:
.
=
2.303/ +1
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 472
Where, .
is the potentiometric selectivity coefficient, E1 is the potential measured in
10−3 mol L−1 CT solution, E2 is the potential measured in 10−3 mol L−1 interferent solution, ZA
and ZB are the charges of CT and interfering ion, respectively, αA is the activity of the drug
and 2.303RT/ZAF represents the slope of the investigated sensor (mV/concentration decade).
3. RESULTS AND DISCUSSION
In ion selective electrodes, the selective membranes show both ion exchange and perm
selectivity for the sensor ion [23]. Taking this in account it is considered advantageous to
create new fabricated electrodes with competitive properties for the determination of CT drug
in its pure substance, drug product and in presence of its alkaline and oxidative degradation
products.
3.1. Sensors fabrication
PVC was used as a matrix in the sensors fabrication being a regular support and
reproducible trap for ion association complexes. PVC requires plasticization and places a
constraint on the choice of mediator [24]. Thus in the present work, the optimum available
mediator for fabrication of sensors was found to be DOP and its proportion was optimized to
minimize the electrical asymmetry of the membrane as to keep the sensor as clean as possible
and to stop leaching into the aqueous phase [25]. The present study originates from the fact
that CT behaves as cation in acid medium as it has dissociation constant (pKa=9.5). This fact
suggests the use of cationic exchangers as PTA, PMA, NaTPB in acid medium as they form
insoluble ion association complexes with suitable grain size with CT. The ratio of CT to the
ion exchangers in the formed complexes was found to be 1:1 as proven by elemental analysis
and the obtained Nernestian slopes (about 60 mV/decade) so CT acts as a monoionic species.
3.2. Sensors calibration and response time
Based on the IUPAC [21] recommendations the response characteristics of the designed
sensors were assessed. Table 1 displays the results obtained over a period of three months for
the three sensors. Typical calibration plots are shown in Fig. 3. The slope was computed from
the linear part of the calibration graph. The slopes of the calibration plots were 49.8±0.45,
52.8±1.0and 47.4±0.30 mV/concentration decades for sensors 1, 2 and 3 respectively. The
deviation from the ideal Nernstian slope (60 mV/ decade), is due to the fact that the
electrodes respond to activities of the drug rather than the concentration. The suggested
electrodes displayed constant potential readings for day to day measurements, and the
calibration slopes did not change by more than ±1.4 mV/decade over a period of 8 weeks.
The dynamic response time is the required time for the sensor to reach values within ±1 mV
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 473
of the final equilibrium potential after increasing the drug concentration 10-fold. The sensors
were able to quickly reach its equilibrium response (10-14 seconds).
Fig. 3. Profile of the potential in mV versus –log concentration of CT in mol L-1 obtained
with sensors 1, 2 and 3
3.3. Precision
To evaluate the precision of measurements, three concentrations within the linear
concentration range (10-4, 10-3 and 10-2, mol L-1 solutions) of CT were chosen. Three
solutions of each concentration were prepared and analyzed in triplicate (repeatability assay).
This assay was repeated on three different days (reproducibility assay), (Table 1).
3.4. Robustness
The method demonstrated efficient stability when the plasticizer was changed to DBP
instead of DOP for sensors 1 and 2. Also, the wide range of pH (3.0-6.0) made the method
robust. Results proved the robustness of the method upon changing the type of the plasticizer
(Table 1).
3.5. Effect of pH
The effect of pH on the response of the proposed sensors was studied. The results showed
that the potential remained constant despite the pH change in the range of 3.0-6.0, which
indicates the applicability of this electrode in the specified pH range. Fig. 4.
Relatively noteworthy fluctuations in the potential versus pH behavior took place below
and above the formerly stated pH limits. In detail, the decrease in potential above the pH
value of 6.0 was due to the gradual decrease in the concentration of the CT mono-cation due
to the formation of the non-protonated dimethyl amino group. Below pH 3, the electrode
response increased with the increase of analyte acidity; the membrane may extract H+,
leading to noisy responses.
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 474
Fig. 4. Effect of pH on the response of the suggested sensors in 10-3 mol L-1 CT
Table 1. Validation of the response characteristics of the investigated sensors
Parameter
Sensor 1
CT-PMA
Sensor 2
CT-PTA
Sensor 3
CT- NaTPB
Slope (mV/ decade) a
49.8±0.45
52.8±1.0
47.4±0.30
Intercept (mV)
103.8±2.0
114.4±1.0
159.4±2.0
Correlation coefficient (r2)
0.9999
0.9996
0.9994
Linearity range (mol L-1)
1×10-6-1×10-2
1×10-6-1×10-2
1×10-5-1×10-2
Response time (S)
14
14
10
Working pH range
3.0-6.0
3.0-6.0
3.0-6.0
Stability (weeks)
8
8
6
LOD (mol L-1)
1×10-6
1×10-6
1×10-5
Average Accuracy (% )±S.D.b
99.8±1.3
99.9±2.3
98.8±2.1
Precision
(RSD%, n=9)
Repeatability
1.5
1.0
2.0
Reproducibility
2.9
2.0
2.3
Robustnessc
2.5
2.8
-
aResults of six determinations
bAverage recovery % of five concentration levels ,each repeated three times.
cRelative standard deviation % of the potential produced by 10-3 mol L-1 solution (n=3) using DBP as
plasticizer instead of DOP for sensors 1 and 2.
3.6. Sensors selectivity
The selectivity of an ion-pair based membrane electrodes depend on the physico-chemical
characteristics of the ion-exchange process at the membranes. The response of the three
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 475
sensors in the presence of susceptible tablet excipients, organic and inorganic related
compounds, was assessed. As it was obvious from Table 2, none of the tested interfering
species had a significant influence on the potentiometric responses of the electrodes towards
CT.
3.7. Potentiometric determination of CT in the presence of its degradation products
CT was completely degraded when heated with 5.0 M NaOH for three hours and when
heated with 30% H2O2 for five hours. Fig. 2 shows the reported alkaline and oxidative
degradation of the drug [26,27]. Table 3 shows the results obtained upon analysis of synthetic
mixtures containing different ratios of intact drug and degradation products. From the
presented results it was obvious that the proposed sensors could be used for selective
determination of intact drug in the presence of up to 20 % degradates.
Table 2. Potentiometric selectivity coefficients .
for CT sensors by separate solution
method
Interferent (10−3 mol L−1)
Selectivity coefficient
a
Sensor 1
CT-PMA
Sensor 2
CT-PTA
Sensor 3
CT- NaTPB
Alkaline degradate
5.8×10
-2
2.6×10
-2
2.3×10
-2
Oxidative degardate
1.1×10
-3
3.0×10
-2
2.1×10
-2
NaCl
2.1×10
-4
2.3×10
-3
5.12×10
-3
KCl
5.3×10
-4
1.5×10
-4
3.3×10
-3
CaCl2
3.7×10
-4
3.3×10
-4
2.13×10
-3
MgCO3
5.8×10
-4
4.1×10
-4
2.2×10
-3
Sucrose
9.3×10
-4
1.0×10
-5
2.45×10
-3
Mannitol
1.4×10
-5
9.5×10
-4
9.7×10
-4
Urea
1.0×10
-5
7.2×10
-4
8.9×10
-4
aEach value is the average of three determinations
3.8. Potentiometric determination of CT in pharmaceutical formulation
As none of the commonly used CT tablet additives show significant interference with the
determination of CT, the new proposed sensors were successfully applied for CT
determination in tablet without prior extraction as shown in Table 4. Results obtained proved
the applicability of the method as demonstrated by the accurate and precise recovery
percentages.
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 476
Table 3. Determination of CT in laboratory prepared mixtures containing different ratios of
CT and its alkaline and oxidative degradation products by the proposed sensors
Ratio of drug: alkaline deg.: oxidative deg.
Drug recovery (%) ± S.D.
a
Sensor 1
CT-PMA
Sensor 2
CT-PTA
Sensor 3
CT- NaTPB
100: 0: 0
99.8±0.8
99.4±1.2
98.3±0.6
90: 5: 5
100.5±1.4
100.6±0.9
100.3±1.4
80: 10: 10
101.3±1.7
100.6±1.2
100.8±1.2
70: 15: 15
101.8±0.9
101.5±0.8
99.7±2.0
60: 20: 20
102.6±1.4
101.8±2.3
98.8±1.7
50: 25: 25
120±2.3
125±2.1
143±1.3
aAverage of three determinations
3.9. Statistical comparison
The results obtained for the determination of CT in tablets were statistically compared to
the reference HPLC method for analysis of CT in pharmaceutical preparation as shown in
Table 4. The calculated t & F values are less than the tabulated ones which reveals that there
is was no significant difference between the compared methods with respect to accuracy and
precision, respectively.
Table 4. Statistical analysis between the results obtained for the determination of CT in
tablets by the proposed sensors and those by the HPLC method
Pharmaceutical preparation
Drug recovery (%) ± S.D.
a
Sensor 1
CT-PMA
Sensor 2
CT-PTA
Sensor 3
CT- NaTPB
HPLC method b
Citalo® tablets
labeled to contain 20.0 mg CT
99.6±0.92 99.8±1.5 99.4±1.7 99.60±0.42
t-test
c
1.5 (2.77)
1.06 (4.3)
1.9 (4.3)
F
c
2.4 (4.3)
4.6 (8.9)
7.4 (8.9)
aAverage of five determinations
bHPLC method supplied by SEDICO company through personal communication, using C18 column, mobile
phase; water: acetonitrile: trifluoroacetic acid (67:33:0.2, v/v/v) and UV detection at 238 nm
cThe values between parenthesis are the theoretical values of t- and F-at P=0.05
4. CONCLUSION
The responses of the fabricated sensors are sufficiently precise, accurate, and they
demonstrate good selectivity for quantitative determination of CT in pure powder, in
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 477
pharmaceutical formulation and in presence of alkaline and oxidative degradation products.
The sensors offer the advantages of fast response, simplicity, elimination of drug
pretreatment or separation steps. Further advantages offered by the PMA and PTA sensors
over the TPB membrane are the higher sensitivity, selectivity and the longer lifetime. The
proposed three sensors can be used as stability indicating for determination of CT in presence
of its degradation products. They can therefore be used for routine analysis of CT in quality-
control laboratories and could compete with the many sophisticated methods currently
available.
REFERENCES
[1] H. Rang, M. Dale, J. Ritter, R. Flower, and G. Henderson, Rang and Dale’s
Pharmacology, Elsevier Churchill Livingstone, Elsevier Inc., Spain (2012).
[2] A. Raza, Chem. Pharm. Bull. 54 (2006) 432.
[3] I. A. Darwish, and I. H. Refaat, J. AOAC Int. 89 (2006) 326.
[4] J. Menegola, M. Steppe, and E. E. S. Schapoval, J. AOAC Int. 91 (2008) 52.
[5] B. Narayana, and K. Veena, J. Mex. Chem. Soc. 54 (2010) 98.
[6] T. G. Halvorsen, S. Pedersen-Bjergaard, and K. E. Rasmussen, J. Chromatogr. A 909
(2001) 87.
[7] Z. Rong, X. Shangyou, X. Hongmei, H. Rui, and X. Zhining, Chin. j. Anal. Chem. 34
(2006) 1384.
[8] J. J. B. Nevado, C. G. Cabanillas, M. J. V. Llerena, and V. R. Robledo, J. Chromatogr.
A 1072 (2005) 249.
[9] J. J. Berzas, C. Guiberteau, M. J. Villasenor, and V. Rodriguez, Anal. Chim. Acta 519
(2004) 219.
[10] M. T. C. Saravanan, C. A. S. Kumar, C. Sudhakar, B. Rajesh, and G. S. Kumar, JASR.
3 (2012) 62.
[11] C. Pistos, I. Panderi, and J. Atta-Politou, J. Chromatogr. B 810 (2004) 235.
[12] R. N. Rao, A. N. Raju, and D.Nagaraju, J. Pharm. Biomed. Anal. 41 (2006) 280.
[13] K. Sujatha, and J. V. L. N. S. Rao, Pharmanest 4 (2013) 1299.
[14] V. K. Gupta, R. Jain, K. Radhapyari, N. Jadon, and S. Agarwal, Anal Biochem. 408
(2011) 179.
[15] M. K. A. El-Rahman, M. R. Rezk, A. M. Mahmoud, and M. R. Elghobashy, Sens.
Actuators B. 208 (2015) 14.
[16] M. Nebsen, G. M. Elsayed, M. Abdelkawy, and S. Z. Elkhateeb, Anal. Bioanal.
Electrochem. 5 (2013) 368.
[17] M. Nebsen, M. K. A. El-Rahman, A. M. El-Kosasy, M. Y. Salem, and M. G. El-
Bardicy, Port. Electrochim. Acta 29 (2011) 165.
[18] E. S. Elzanfaly, and M. Nebsen, Anal. Bioanal. Electrochem. 5 (2013) 166.
Anal. Bioanal. Electrochem., Vol. 7, No.
4
, 2015, 466-478 478
[19] F. Faridbod, M. R. Ganjali, R. Dinarvand, S. Riahi, P. Norouzi, and M. B. A. Olia,
JFDA. 17 (2009) 264.
[20] T. A. Ali, G. G. Mohamed, A. M. Al-Sabagh, and M. A. Migahed, Chin. j. Anal. Chem.
42 (2014) 565.
[21] IUPAC Analytical Chemistry Division, Commission on Analytical Nomenclature, Pure
Appl. Chem.72 (2000).
[22] T. S. Ma, and S. S. M. Hassan, Organic analysis using ion-selective electrodes,
Academic Press, London (1982).
[23] G. Moody, and J. Thomas, Selective ion sensitive electrodes, chapter 1, Merrow
technical library (1971).
[24] A. M. El-Kosasy, M. A. Shehata, N. Y. Hassan, A. S. Fayed, and B. A. El-Zeany,
Talanta 66 (2005) 746.
[25] H. M. A. Shawish, A. M. Khedr, K. I. Abed-Almonem, and M. Gaber, Talanta 101
(2012) 211.
[26] S. R. Dhaneshwar, and M. V.Mahadik, J. AOAC Int. 92 (2009) 138.
[27] R. N. Rao, A. N. Raju, and R. Narsimha, J. Sep. Sci. 31 (2008) 1729.
Copyright © 2015 by CEE (Center of Excellence in Electrochemistry)
ANALYTICAL & BIOANALYTICAL ELECTROCHEMISTRY (http://www.abechem.com)
Reproduction is permitted for noncommercial purposes.
