Talanta 193 (2019) 9–14

Contents lists available at ScienceDirect

Talanta

journal homepage: www.elsevier.com/locate/talanta

Graphene nanoplatelets in potentiometry: A nanocomposite carbon paste T and

PVC based membrane sensors for analysis of Vilazodone HCl in plasma and
milk samples
Amira M. El-Kosasy, Mona Hamdy Abdel Rahman, Sarah H. Abdelaal
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

ARTICLE INF O AB STRACT

Keywords: Graphene is the ''new star'' material for electrochemical sensing. It has unique mechanical, thermal and electrical
Graphene nanoplatelets properties, in addition to its ultra light weight. In the present work we combine for the first time the special features
Ion selective electrodes offered by graphene and the advantages of ion selective potentiometric sensors in a single study. We propose two
Vilazodone HCl types of sensors, a graphene based carbon paste and a poly vinyl chloride (PVC) based membrane sensors for
Poly vinyl chloride
the analysis of Vilazodone hydrochloride in bulk, human plasma and formula milk samples. Electro active agent is
Bio analysis
an ion- association complex based on coupling of Vilazodone cationic cite with anionic cite of Molybdate ion in a
ratio 1:1. Both sensors are evaluated according to the IUPAC recommendation data, revealing linear response in
−7 −3 −8 −3
the concentration range 10 − 10 and10 − 10 M with a Nernestian slope 59.89 and 59.91 mV/decade for
PVC membrane and Carbon paste sensors, respectively. Both sensors were successfully applied to the analysis of
Vilazodone HCl in human plasma and formula milk samples showing good recovery percentage values. Graphene
based carbon paste sensor shows several advantages over conventional PVC membrane sensor regarding lower
limit of detection, faster response time, longer life time and higher selectivity towards target ion.

1. Introduction
Vilazodone, a new antidepressant with a novel mechanism of
action, is approved by the FDA in January 2011 for the treatment of
major depressive disorder (MDD) [1].
It is suggested that the MDD results from disregulation of serotonin (5-
HT) and nor-epinephrine neurotransmission. Vilazodone is a dual acting
serotonin re-uptake inhibitor and serotonin receptor (5-HT1A) partial
agonist. It augments the availability of serotonin at both pre-and post
synaptic sites, thus producing an antidepressant effect. That's why it has
been termed a SPARI drug. It has a rapid onset of action with minimal
effects on sexual function [2]. The recommended dose is 40 mg once daily.
Steady state plasma concentration is 156 ng/ml, achieved within 3 days of
40 mg daily dosing under fed conditions. It is ex-tensively metabolised in
liver mainly be the CYP-450 3A4 isoenzyme. Non-CYP mediated
metabolism occurs by carboxylesterase. Only 1% and 2% of the dose are
recovered in urine and faeces respectively as unchanged Vilazodone. It is
excreted into the milk of lactating rats [3].
The misuse of antidepressants by women suffering post-partum
depression made it important to determine the extent of drug excretion
in breast milk. Till now, the manufacturer declared that Vilazodone
enters rodent milk. Till then, the effect of Vilazodone on lactation and
nursing in human is unknown. However, all psychtropics that pass into
the brain easily are assumed to be excreted in breast milk [4].
A literature review survey reveals several published methods for
analysis of Vilazodone in bulk, pharmaceutical dosage form and
plasma samples and stability indicating assays including UV–visible
spectro-photometric methods [5–10], spectrofluorimetric methods [11]
and high performance thin layer chromatographic methods (HPTLC)
[12]. Also high performance liquid chromatographic methods have
been re-ported either with UV [13–18], fluorescence [11] or mass [19–
23] detection. The literature is devoid of any electrochemical methods
for analysis of Vilazodone.
Ion selective electrodes (ISEs) are the chemical sensors with the
longest history, that they have reached the commercial stage. They
have found a vast range of applications in clinical, industrial and en-
vironmental analysis. They offer a number of potential benefits being
simple, specific to the drug of interest, sensitive, cheap, fast and ap-
plicable to complex samples without pre-treatment steps. ISEs are one
of the greenest analytical techniques with regard to solvent

Corresponding author.
E-mail address: sarah.hamdy19@gmail.com (S.H. Abdelaal).

https://doi.org/10.1016/j.talanta.2018.09.091
Received 6 July 2018; Received in revised form 20 September 2018; Accepted 24 September 2018
Available online 25 September 2018
0039-9140/ © 2018 Elsevier B.V. All rights reserved.
A.M. El-Kosasy et al.
consumption [24]. One of the most common existing approaches in
developing ISEs for organic drug species is the incorporation of a li-
pophillic ion-pair complex in a highly plasticized PVC membrane
[25,26].
Upon the streaming progress in this field, Mesaric and Damen
were probably the first to use electrodes filled with carbon pastes [27].
Since then, Carbon paste electrodes (CPEs) have attracted great
attention because they offer several advantages over the conventional
membrane electrodes including: renewability, chemical inertness,
stable response, ease of chemical or biological modification, low ohmic
resistance and no need for internal filling solution [28]. Carbon paste is
a mixture of graphite powder, electro active material and a suitable
non-conductive liquid binder with the incorporation of carbon
nanomaterials as a re-cent trend [29].
In 2004, graphene was reported to be obtained at university of
Manchester in the UK. Since then, it has received great attention in dif-
ferent fields of analysis. Graphene is composed of Sp2 – hybridized carbon
network in the form of a flat two dimensional sheet arranged in a hex-
agonal configuration. It offers unique mechanical, thermal and electrical
properties, in addition to its ultra light weight. These sheets are good
conductors of heat and electricity. Its good mechanical adhesion is mainly
due to high contact area obtained by the unrolled sheets. This high surface
area provides a high capacity of accumulation especially molecules with π
electron structure which are expected to adhere with Sp2 structure of
graphene through π –π interactions.
Graphene has been a great candidate for the use in sensing applica-
tions. The key step is immobilization of biomolecules or electro active
materials on its surface for their further use as recognition elements. This is
either achieved through physical adsorption or entrapment within carbon
network or covalent interaction by chemical reaction [30,31]. Graphene has
been used for the analysis of various biologically important molecules as
dopamine, glucose, NADH and caffeine using Voltammetric techniques.
However, voltammetry has the disadvantage of interference from other
compounds having close oxidation potential [32].
Thus, in this work we combine for the first time the advantages of
graphene with those of ion selective potentiometric sensors. We pro-
pose two types of potentiometric sensors for the analysis of
Vilazodone HCl in bulk, human plasma and formula milk samples.
Both are based on ion-pair formed through coupling of Vilazodone
cationic site with ammonium Molybdate as anionic exchanger. The first
sensor is PVC-based membrane. The second is a new carbon paste
sensor based on graphene nanoplatelets which is designed to improve
the mechanical stability and analytical responses.
2. Experimental
2.1. Apparatus
Ag/AgCl double-junction – type external reference electrode
(Thermo Scientific Orion 900200, (MA, USA); 3.0 M KCl saturated with
AgCl as an inner filling solution and 10% KNO3 as a bridge electrolyte)
and Jenway digital ion analyzer (model 3330; Essex, UK) were used
for potentiometric measurements.
For pH adjustments, a Jenway pH glass electrode no. 924005-
BO3-Q11C (Essex, UK) was used.
For temperature adjustments, a Bandelin Sonorex magnetic stirrer
and heater, model Rx510S (Budapest, Hungaria) was used.
2.2. Chemicals and reagents
All chemicals and reagents used were of analytical grade and water
was bi-distilled. Poly vinyl chloride (PVC) was obtained from Fluka
(Steinheim, Germany). Tetra hydro furan (THF) and di-methyl Sulphoxide
(DMSO) were purchased from Merck (Dermstadt, Germany). Graphene
nanoplatelets and Di-octyl phthalate (DOP) were purchased from Sigma
Aldrich (Steinheim, Germany). Ammonium Molybdate was purchased
10
Talanta 193 (2019) 9–14
from BDH chemicals Ltd (Poole, England). Calcium Chloride (CaCl2),
Hydrochloric acid (HCl), Sodium Hydroxide (NaOH), Sodium Chloride
(NaCl), Potassium Chloride (KCl), Lithium Bromide (LiBr), Magnesium
sulphate (MgSO4) and Thiamine HCl were purchased from Prolabo
(Pennsylvania, USA). Metoclopramide HCl was kindly supplied by
National Organisation of Drug Research and Control (NODCAR).
Liquid Paraffin was obtained from El Nasr Company (Cairo, Egypt).
Vilazodone HCl and Dextromethorphane HBr were kindly supplied
by El-Hikma Pharmaceuticals Co., Cairo, Egypt. Vilazodone HCl was
certified to contain 99.10%.
Fresh plasma samples were purchased from VACSERA (Cairo,
Egypt). Formula milk Similac 1® was purchased from the local market.
2.3. Standard solutions
−3
Stock solution (1 × 10 M) was prepared by dissolving the re-
quired amount of Vilazodone HCl in the least amount of DMSO and
then the volume was completed to 100 ml using bi- distilled water.
−9 −3
Working solutions (1 × 10 – 1 × 10 M) were prepared by
appropriate dilution from the previously mentioned stock solution (1 ×
−3
10 M) using bi- distilled water.
3. Procedures
3.1. Preparation of the ion-association complex
The sensing element was prepared by mixing 100 ml of Vilazodone
−3
10 M stock solution with 100 ml of a saturated Molybdate aqueous
solution. The resulting yellowish white precipitate was filtered, washed
using distilled water, dried at room temperature and ground to fine
powder. A sample of the sensing element was sent for elemental ana-
lysis.
3.2. Sensors fabrication
3.2.1. PVC membrane sensor (sensor 1)
In a 5 cm glass Petri- dish, 0.01 gm ion pair complex, 0.35 ml DOP
plasticizer and 0.19 gm PVC matrix were mixed thoroughly then dis-
solved in 5 ml THF. The solvent was allowed to evaporate slowly at
room temperature.
The membrane (8 mm diameter) was cut out and glued to the po-
lished end of polyethylene tubing using THF.
The electrode body consisted of a glass tube to which poly
ethylene tube was tightly attached at one end and filled with an internal
−3
re-ference solution (an equimolar mixture of 10 M KCl and
Vilazodone). Ag/AgCl wire (1 mm diameter) was immersed in the
internal reference solution.
−3
The membrane was conditioned by soaking in 10 M Vilazodone
−7
solution overnight before measurements. It was soaked in 10 M
Vilazodone solution when not in use.
3.2.2. Carbon paste sensor (sensor 2)
In a mortar, 0.02 gm ion pair and 0.30 gm graphene nanoplatelets were
homogenized into a smooth paste with the aid of liquid paraffin. The paste
was carefully packed into a plastic tube (4 mm diameter) to avoid possible
air gaps and a copper wire (1 mm diameter) was inserted into the opposite
end to establish electrical contact. External surface of the elec-trode was
smoothed using a soft paper. The electrode was conditioned by soaking in
−3
10 M Vilazodone solution overnight before measurements.
3.3. Cell assembly
−3
Ag-AgCl ǁ internal solution, equimolar mixture of 10 M KCl and
Vilazodone | PVC membrane | sample solution ǁ Ag-AgCl, KNO3 (sa-
turated)
CPE| sample solution || Ag-AgCl, KCl (saturated)
A.M. El-Kosasy et al. Talanta 193 (2019) 9–14

3.4. Sensors calibration

The conditioned electrodes were immersed separately in 50 ml of

each of working standard solutions and the measured emf values
within ± 1 mV were recorded. The electrodes were washed with water
between measurements. Fresh surface of the paste was obtained by
squeezing more out and polishing the surface with filter paper.
The recorded emf was plotted as a function of negative logarithmic
Vilazodone concentration and regression equation for each sensor
was computed for the linear part of the curve.
3.5. Application to spiked human plasma and formula milk samples

Spiked human plasma and formula milk samples were prepared by

appropriate dilution of working solutions using plasma and recon-
stituted formula milk respectively. The electrodes were immersed se-
parately in the prepared samples and emf was recorded. The
electrode was washed with water between measurements. The emf
values pro-duced were recorded and the concentration was calculated Fig. 1. Chemical Structure of (a) Vilazodone showing its cationic site and (b)
from the previously computed regression equation. Results are
Ammonium Hepta Molybdate showing its anionic site.
expressed as re-covery % ± SD.

3.6. Studying matrix effect
In order to study the interference of plasma and milk matrices with
the performance of the proposed sensors, two calibration curves were
constructed for each sensor using different concentrations of spiked
human plasma and spiked formula milk samples. The electrodes were
washed with water between measurements. The recorded emf was
plotted as a function of negative logarithmic spiked Vilazodone con-
centration and regression equations for each sensor were computed
for the linear part of the curve. Then matrix effect, which is the
observed increase or decrease in response of the proposed sensors
due to inter-ference of matrix components, was calculated.
4. Results and discussion
4.1. Sensors fabrication
Vilazodone is an HCl salt having a pKa = 7.1. It has a protonated
piperazine ring in its structure that acts as a cationic exchanger. The
proposed study was based on coupling of cationic site in Vilazodone
HCl with an anionic exchanger. Molybdate was the optimum counter
ion for Vilazodone precipitation. The protonated piperazine ring was
found to have a high affinity towards the formation of an ion-pair
complex with the oppositely charged Molybdate ion (Fig. 1) in a ratio
1:1, as proven by the results of elemental analysis and the obtained
Nernestian slopes. Molybdate was chosen because of its availability
and remarkable stability of the formed complex. This ion association
com-plex was water insoluble but readily soluble in organic solvents
Carbon paste sensor is made of graphene nanoplatelets instead of
graphite powder with ion pair homogenously incorporated inside the
paste with the aid of liquid paraffin as binding agent.
4.2. Performance characteristics of PVC based membrane and carbon
paste sensors
The electrochemical performance of the proposed sensors was
evaluated according to the IUPAC recommendation data and summar-
ized in Table (1).
Slopes of the calibration plots are 59.89 and 59.91 mV/ decade with
−7 −3 −8 −3
linearity ranges 10 –10 and 10 –10 M for sensors 1 and 2 re-
spectively. (Fig. 2) Limits of detection were calculated from the extra-
polated linear segments of the calibration plots. Response time is essential
since a fast response allows analysis of a large number of samples in a
short time. It was found to be 20 and 5 s for sensors 1 and 2 respectively.
Life time is 22 and 40 days for sensors 1 and 2 respectively (Fig. 3). Longer
stability of carbon paste sensor is owed to surface renewability.
4.3. Studying matrix effect
Inherent variability of the matrix composition of different biological
samples may result in unspecific interferences and even may cause
Table 1
General characteristics of the proposed sensors.
Parameter Sensor 1 Sensor 2

such as tetrahydrofuran. Slope (mV/decade) 59.89 59.91

The choice of Plasticizer is a crucial step. It is a water-immiscible Intercept (mV) 479.87 499.49
high boiling organic solvent that plasticizes the membrane, acts as a LOD (M) 9.8 × 10–8 1 × 10–8
LLOQ (M) 10–7 10–8
solvent for ion-pair and adjusts permittivity and ion exchanger sites
Response time (s) 20 5
mobility. Di-octyl phthalate was the chosen available plasticizer giving Working PH range 3–6.5 3–7
the highest possible sensitivity and selectivity. Phthalates are the most Concentration range (M) 10–7 – 10–3 10–8 – 10–3
commonly used plasticizers. They are esters of polycarboxylic acids Stability ( days) 22 40
with either linear or branched aliphatic alcohol. The plasticizer embeds Average recovery ( ± SD) 99.9 ± 1.4 100.3 ± 1.7
Correlation coefficient 0.9998 1
itself between the polymer chains, spacing them apart. Thus, the free
Intra-assay precision (%RSD) 1.04 0.79
volume increases, imparting the desired durability and flexibility [33]. Intermediate precision* (%RSD) 1.77 2.01
Nitro aromatic mediator NOPE with high dielectric constant gave the Average recovery in human plasma samples 100.3 ± 1.1 99 ± 1.2
same effect as DOP, whereas dibutyl sebacate gave noisy responses (mean ± SD) 99 ± 2 100 ± 1.8
with little discrimination of concentration changes. Average recovery in formula milk samples
(mean ± SD)
The proposed PVC based membrane sensor is composed of PVC
matrix, DOP as plasticizer and ion pair as sensing element in a ratio * Intermediate precision studied by analysis of different concentration levels of
37: 61: 2 (% W/W). Vilazodone on three different days.

11
A.M. El-Kosasy et al.
Fig. 2. a Profile of the potential in mV versus – Log [vil] using the proposed PVC
based membrane sensor. b Profile of the potential in mV versus – Log [vil] using
the proposed carbon paste sensor.
permanent damage of the electrode surface. Thus, effect of the studied
plasma and milk matrices on the performance of the proposed sensors was
evaluated. For PVC based membrane sensor, the constructed cali-bration
curves showed slope values 59.95 and 59.90 mV/decade and intercept
values 481.45 and 478.13 mV for plasma and milk matrices; respectively.
For CP sensor, the constructed calibration curves showed slope values
59.90 and 59.96 mV/decade and intercept values 499.11 and 499.95 mV
for plasma and milk matrices; respectively. Calibration curves showed the
same LOD and linearity range values as those ob-tained in aqueous
medium. Then Matrix Effects (MEs) were calculated from calibration curve
slopes in aqueous medium and in matrix ac-cording to the following
equation:[34,35]
ME% = (S matrix / S aqueous − 1)*100
The values of ME between + 20% and – 20% are considered as a low
matrix effect. Results obtained (Table 2) showed no matrix effect, thus
proving insignificant interference of the different tested matrices on the
performance of the proposed sensors. This boosts the advantage of using
ISEs without complex sample extraction procedures.
4.4. pH study
Effect of pH on the response of the proposed sensors was studied.
pH was adjusted in the range 1–9 using small volumes of 1 M HCl and
NaOH. Response was stable in the ranges 3–6.5 and 3–7 for sensors
1 and 2 respectively.
The observed potential changes at lower and higher pH values are
due to interference from hydronium and hydroxyl ions which are pre-
sent at relatively higher concentration than the primary ion. Also at
high pH values, the Vilazodone HCl base precipitated accounting for
the observed potential changes.
For sensor 2, at low pH values where hydronium ion concentration
is high, physisorption occurs through van der Waal interactions with
high electron density graphene sheets. This accounts for the observed
abnormally higher potentials. (Fig. 4)
12
Talanta 193 (2019) 9–14
Fig. 3. Profile of the slope in mV/decade versus time in days to study stability of
(a) PVC and (b) CP sensors.
Table 2
Results of Matrix Effect (ME %) on performance of the proposed sensors.
Sensor 1 Sensor 2
Plasma 0.1 − 0.02
Milk 0.02 0.08
4.5. Sensors selectivity
The selectivity is one of the most important characteristics of ISEs.
It indicates the specificity of the sensor towards the target ion in the
presence of complex matrices of interfering components. Hence, the
influence of some interferents on the electrodes response was in-
+ + + +2
vestigated. Inorganic cations Na , K , Mg and Ca were studied as
examples of electrolytes present in plasma and milk matrices. Lithium
is a frequently co-administered mood stabilizer with antidepressants.
Also some organic cations as Thiamine HCl, Metoclopramide HCl and
Dextromethorphane HBr were studied as examples of co-administered
drugs. The selectivity coefficients were calculated using the SSM, in
which the re-arranged Nicolsky-Eisenman equation was employed.
Log Kpot A, B = [(EB – EA)/ S] + (1 – ZA / ZB)] Log [A]
−4
Where: EA is the electrode potential of 10 M Vilazodone HCl
−4
solution, EB is the electrode potential of 10 M solution of Interferent
ion, S is the slope of calibration curve.
Results are shown in Table 3. The smaller the K value, the less
impact the interfering ion will have on the measured potential. Ob-
tained results show excellent selectivity of proposed sensors towards
A.M. El-Kosasy et al. Talanta 193 (2019) 9–14

Table 4
statistical comparison between the determination of Vilazodone in human plasma
samples by the proposed sensors and the reference published method.
Parameter Sensor 1 Sensor 2 Published method [20]

Mean % 100.3 99 99.7

SD 1.1 1.2 2
Variance 1.29 1.47 4.04
N 3 3 4
Students t-test (2.57)* 0.46 0.67 –
F-test (19.16)* 3.13 2.75 –

[20] UPLC–MS-MS Method for the Determination of Vilazodone in Human

Plasma: Application to a Pharmacokinetic Study.
* The figures in parenthesis are the corresponding theoretical values for F and
t at p = 0.05.

5. Conclusion

In the present study, we report a new type of graphene based

carbon paste sensor for use in Potentiometry. It involves the use of
Ammonium Molybdate-Vilazodone ion association complex as the
electro active material. The new sensor is compared to a PVC based
Fig. 4. a Effect of pH on the proposed PVC based membrane sensor. b Effect of sensor and both were used for the analysis of Vilazodone HCl in bulk,
pH on the proposed carbon paste sensor. human plasma and formula milk samples. The electrodes showed
−9 −3
linear dynamic re-sponse in the concentration range 10 –10 and
Table 3 −8 −3
10 –10 M with a Nernestian slope 59.89 and 59.91 mV/decade for
potentiometric selectivity coefficients (Log Kpot Vilazodone, Interferent) for the PVC and Carbon paste sensors respectively.
proposed sensors: . Graphene based sensor offers several advantages over the
Interferent Sensor 1 Sensor 2 proposed PVC membrane based sensor in terms of faster response
NaCl − 0.083 − 2.15 allowing ana-lysis of larger number of samples in a short time, longer
KCl − 1.467 − 3.40 life time, lower limit of detection, wider linear dynamic range and
LiBr − 0.382 − 3.03
higher selectivity towards the target ion.
MgSO4 − 3.709 − 2.30
CaCl2 − 3.484 − 4.67 Declarations of interest
Thiamine HCl 0.001 − 4.11
Metoclopramide HCl − 1.150 − 0.60
Dextromethorphane HBr − 0.081 − 3.64 None

the target ion with no significant interference on performance. We can
conclude that inorganic cations don’t interfere owing to the difference
in ionic size and consequently their mobilities and permeability. It was
observed that the proposed carbon paste electrode exhibits lower se-
lectivity coefficient values than the described PVC based membrane
sensor, thus higher selectivity towards target ion.
4.6. Application to spiked human plasma and formula milk samples
The proposed sensors were successfully applied for the analysis of
Vilazodone in human plasma and formula milk samples without pre-
treatment. Formula milk was chosen as a best simulation for human
milk. It has the same composition of breast milk except for antibodies,
hormones, growth factors and enzymes. Accurate and precise
recoveries were obtained as shown in Table 1.
4.7. Statistical comparison
To examine the validity of the proposed sensors, the results obtained
were statistically compared to those of UPLC-MS-MS published method
[20], using student's t-test and variance ratio F-test at p = 0.05. The
calculated t- and F-values didn’t exceed the theoretical values, which
indicate that there is no significant difference between mean and var-iances
of both methods in the determination of Vilazodone in human plasma.
However, the proposed sensors offer the great advantage of lower cost
than the published UPLC-MS-MS method. (Table 4)
13
References
[1] D. Anderson, NEW drug: Vilazodone (Viibryd ®), Soc. Forensic Toxicol. ToxTalk.
36 (2012) 1–2.
[2] L.A. Dawson, J.M. Watson, Vilazodone: a 5-HT1A receptor agonist/serotonin
transporter inhibitor for the treatment of affective disorders, CNS Neurosci. Ther.
15 (2009) 107–117, https://doi.org/10.1111/j.1755-5949.2008.00067.x.
[3] M.P. Cruz, Vilazodone HCl (Viibryd): a serotonin partial agonist and reuptake in-
hibitor for the treatment of major depressive disorder, P T. 37 (2012) 28–31
〈http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3278186&tool=
pmcentrez&rendertype=abstract〉.
[4] T.W. Hale, H.E. Rowe, Medications and Mothers’ Milk 2017, 17th ed., Springer
Publishing Company, 2017.
[5] S.S. Panda, B.V.V.R. Kumar, S. Beg, Soumyajit Behera, Spectrophotometric
quan-tification of Vilazodone hydrochloride in pharmaceutical dosage form using
quality By design approach, Malays. J. Anal. Sci. 19 (2015) 920–929 .
[6] S. Ghosh, S. Bomma, V.L. Prasanna, D.D. Banji, Development of validated UV-
Spectrophotometric method for the estimation of Vilazodone hydrochloride, Int. J.
Drug Deliv. Res. 6 (2014) 280–285.
[7] K.R. Vivekkumar, F.C. Chetan, D.P. Pritam, J.S. Sanjay, Development and
validation of spectroscopic methods for the estimation of Vilazodone in bulk and
in tablet formulation, J. Pharm. Res. 13 (2014) 20–22.
[8] B. Srinivas, P. Yadagiriswamy, G. Venkateswarlu, Spectrophotometric determina-
tion of drugs in bulk and pharmaceutical dosage form by using P-Chloranilic acid,
Int. J. Pharm. Res. Bio-Sci. 4 (2015) 213–228.
[9] B. Srinivas, P. Yadagiriswamy, G. Venkateswarlu, Spectrophotometric
determina-tion of drugs In bulk And tablet form By using 2,3-dichloro-5,6-
dicyano-1,4-ben-zoquinone, Int. J. Anal. Bioanal. Chem. 5 (2015) 88–93.
[10] B. Thangabalan, S.S. Fathima, R.L. Narusu, S.M. Babu, UV spectrophotometric
es-timation of Vilazodone in pure and tablet dosage form, Asian J.
Pharamceutical Res. 5 (2015) 126–127.
[11] R.I. El-bagary, H.A.E.M. Hashem, M.A. Fouad, Sally tarek mahmoud,
development and validation of spectrofluorimetric and RP-HPLC with fluorimetric
detection methods for the determination of vilazodone in bulk and pharmaceutical
prepara-tion, Int. J. Pharm. Res. Sch. 3 (2014) 113–119,
https://doi.org/10.4172/2155-9872.1000233.
[12] K.R. Vivekkumar, F.C. Chetan, J.S. Sanjay, Development and validation of HPTLC/
A.M. El-Kosasy et al.
Densitometry method for the estimation of Vilazodone HCl in bulk drug and tablet
formulation, J. Pharm. Res. 13 (2014) 71–73.
[13] B.P. Reddy, N. Pramod, P. Venkateswararao, A.S. Babu, Method development
and validation for the assay of Vilazodone in bulk and formulation by using RP-
HPLC technique, Int. J. Biol. Pharm. Res. 3 (2012) 789–795 .
[14] G. VenkataSubbaiah, G. Devika, R. Salibai, K. Hemalatha, S.G. Krishna,
Determination of vilazodone in pharmaceutical formulations by HPLC method, J.
Glob. Trends Pharm. Sci. 5 (2014) 2261–2264.
[15] S. Ghosh, S. Venkatesh, B.V.V. Ravikumar, Development of stability indicating
RP-HPLC method and validation for the estimation of vilazodone hydrochloride,
Int. J. PharmTech Res. 7 (2015) 204–211 .
[16] K. Chikhalia, S. Mehta, S. Singh, H. Patel, Isolation and structure elucidation of
major alkaline degradation product of vilazodone, Int. J. Pharm. Sci. Rev. Res. 29
(2014) 180–183.
[17] P.D. Kalariya, M.V.N.K. Talluri, S. Ragampeta, Experimental design approach for
selective separation of vilazodone HCl and its degradants by LC-PDA and char-
acterization of major degradants by LC/QTOF–MS/MS, Chromatographia 77
(2014) 1299–1313, https://doi.org/10.1007/s10337-014-2739-0.
[18] P.D. Kalariya, M.V.N.K. Talluri, P.N. Patel, R. Srinivas, Identification of hydrolytic
and isomeric N-oxide degradants of vilazodone by on line LC-ESI-MS/MS and
APCI-MS, J. Pharm. Biomed. Anal. 102 (2015) 353–365,
https://doi.org/10.1016/j.jpba. 2014.09.033.
[19] W. Sui, X. Yang, W. Yu, Y. Jin, X. Luan, X. Wang, H. Xu, A validated LC-MS/MS
method for the rapid quantification of vilazodone in rat plasma: application to a
pharmacokinetic study, J. Pharm. Biomed. Anal. 98 (2014) 228–234, https://doi.
org/10.1016/j.jpba.2014.05.034 .
[20] R. El-Bagary, H. Hashem, M. Fouad, S. Tarek, UPLC-MS-MS method for the
de-termination of vilazodone in human plasma: application to a
pharmacokinetic study, J. Chromatogr. Sci. 54 (2016) 1365–1372,
https://doi.org/10.1093/ chromsci/bmw084 .
[21] P. Sistik, R. Urinovska, H. Brozmanova, I. Kacirova, P. Silhan, K. Lemr, Fast si-
multaneous LC/MS/MS determination of 10 active compounds in human serum
for therapeutic drug monitoring in psychiatric medication, Biomed. Chromatogr.
30 (2016) 217–224, https://doi.org/10.1002/bmc.3538.
[22] B.B. Chavan, P.D. Kalariya, S. Tiwari, R.D. Nimbalkar, P. Garg, R. Srinivas,
M.V.N.K. Talluri, Identification and characterization of vilazodone metabolites in
rats and microsomes by ultrahigh-performance liquid chromatography/quadrupole
time-of-flight tandem mass spectrometry, Rapid Commun. Mass Spectrom. 31
(2017) 1974–1984, https://doi.org/10.1002/rcm.7982.
14
Talanta 193 (2019) 9–14
[23] M. Iqbal, E. Ezzeldin, K.A. Al-Rashood, A.A. Bajrai, A simple and fast UHPLC-
MS-MS assay for rapid determination of vilazodone in plasma sample, J. Anal.
Toxicol. 39 (2015) 106–112, https://doi.org/10.1093/jat/bku126 .
[24] A.K. Hassan, S.T. Ameen, B. Saad, Tetracaine – selective electrodes with polymer
membranes and their application in pharmaceutical formulation control, Arab J. Chem.
10 (2017) S1484–S1491, https://doi.org/10.1016/j.arabjc.2013.04.029.
[25] V.K. Gupta, A. Nayak, S. Agarwal, B. Singhal, Recent advances on potentiometric
membrane sensors for pharmaceutical analysis, Comb. Chem. High. Throughput
Screen. 14 (2011) 284–302, https://doi.org/10.2174/138620711795222437.
[26] R.P. Buck, V.V. Cosofret, Design of sensitive drugsensors: principles and
practice, Fundam. Appl. Chem. Sensors, 1986, pp. 363–372.
[27] S. Mesaric, E.A.M.F. Dahmen, Ion selective carbon paste electrodes for halides
and silver ions, Anal. Chim. Acta 64 (1973) 431–438 .
[28] M.R. Ganjali, H. Khoshsafar, F. Faridbod, A. Shirzadmehr, M. Javanbakht,
P. Norouzi, Room temperature ionic liquids (rtils) and multiwalled carbon nano-
tubes (mwcnts) as modifiers for improvement of carbon paste ion selective elec-
trode response; a comparison study with pvc membrane, Electroanalysis 21
(2009) 2175–2178, https://doi.org/10.1002/elan.200904642.
[29] Z. Staniü, S. Girousi, Carbon paste electrodes in potentiometry: the state of the
art and applications in modern electroanalysis (A Review), 2011.
[30] B. Pérez-López, A. Merkoçi, Carbon nanotubes and graphene in analytical sciences,
Microchim. Acta 179 (2012) 1–16, https://doi.org/10.1007/s00604-012-0871-9.
[31] M.S. Goh, M. Pumera, Graphene-based electrochemical sensor for detection of
2,4,6- trinitrotoluene (TNT) in seawater: the comparison of single-, few-, and
multilayer graphene nanoribbons and graphite microparticles, Anal. Bioanal.
Chem. 399 (2011) 127–131, https://doi.org/10.1007/s00216-010-4338-8.
[32] Hossein Bahramipur, F. Jalali, Sensitive determination of paracetamol using a
graphene-modified carbon- paste electrode, Afr. J. Pharm. Pharmacol. 6
(2012) 1298–1305, https://doi.org/10.5897/AJPP12.212.
[33] M.M. Zareh, Plasticizers and their role in membrane selective electrodes, Recent
Adv. Plast. (2012) 113–124 〈http://www.intechopen.com/books/recent-advances-
in-plasticizers/plasticizers-and-their-role-in-membrane-selective-electrodes 〉.
[34] A. Economou, H. Botitsi, S. Antoniou, D. Tsipi, Determination of multi-class pesti-
cides in wines by solid-phase extraction and liquid chromatography-tandem mass
spectrometry, J. Chromatogr. A 1216 (2009) 5856–5867, https://doi.org/10.1016/
j.chroma.2009.06.031.
[35] M. Farouk, L. Abd, E. Aziz, N. Fathy, E. Azab, Analytical Methods insecticide re-
sidues and their metabolite in liquid chromatography with diode-array detection,
Anal. Methods 8 (2016) 4563–4575, https://doi.org/10.1039/C6AY01161F.