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Bulletin of Environment, Pharmacology and Life Sciences
Bull. Env. Pharmacol. Life Sci., Vol 5 [6] May 2016: 48-52
Academy for Environment and Life Sciences, India
Online ISSN 2277-1808
Journal's URL:http://www.bepls.com
Global Impact Factor 0.533
Universal Impact Factor 0.9804
Ion-selective Electrode Determination of Venlafaxine
Hydrochloride in pure form and Capsules
Lamia A. Al-bedair
Department of Chemistry, College of Science, Princess NourahBint Abdul Rahman University Email: laalbedair@pnu.edu.sa Venlafaxine ion-selective electrode was constructed from poly(vinyl chloride) containing venlafaxine-silicomolybdate
(VE-SMA) as the sensing element in the presence of DOP as the plasticizing solvent mediator.The best PVC membrane
electrode was made of a composition of 46% PVC, 46% DOP and 8% ion-pair.The electrode showed a fast, stable and
Nernstian response over a wide venlafaxine concentration range 1.0×10-2- 1.0×10-6mol/L of the drug concentration with
the slope of 58.8 mV/decade. The electrode exhibit good selectivity for the VE with respect to a large number of inorganic
cations and organic substances of biological fluids. The method is precise as shown by the mean recoveries range of
99.69–101.94% with mean relative standard deviations 0.51–1.40%. Venlafaxine is determined successfully in pure
solutions and in capsules using the standard additions and potentiometric titrations methods.
Keywords: Venlafaxine hydrochloride (VE) ; Ion-selective electrode ;Potentiometry.

Received 31.01.2016
Revised 16.03.201 Accepted 04.04.2016

Venlafaxine hydrochloride Figure 1, (1-[2-dimethylamino)-1-(4-methoxy phenyl) ethyl] cyclohexanol)
hydrochloride is a third-generation, structurally novel phenethyl bicyclic antidepressant [1]. Venlafaxine
inhibits synaptosomal re-uptake of both serotonin and noradrenalin, and it is also a relatively weak
inhibitor of dopamine re-uptake [2]. There are several methods reported for the determination of
venlafaxine in biological fluids [3-6] However, for its determination in drug formulations only two
methods have been reported [7-9]. Most of these methods use sophisticated instruments, time consuming
or needs expensive reagents.
Ion-selective electrodes have been increasingly used for quantitative measurement of drugs.
Potentiometric methods based on this technique are simple, rapid, low cost, low detection limit, good
accuracy, wide concentration range, applicability to coloured and turbid solutions and offer enough
selectivity towards the drugs in the presence of various pharmaceutical excipients [10,11].The present
investigation deals with the fabrication and characterization of liquid membrane ion selective electrode
for the determination of venlafaxine hydrochloride . The electrochemical sensitivity of the electrode is
based on the incorporation of venlafaxine-silicomolybdate (VE-SMA) as a sensing element. The electrode
was successfully applied for the determination of venlafaxine hydrochloride in pure form and in capsules.
Figure 1. Chemical structure of venlafaxine hydrochloride.
BEPLS Vol 5 [6] May 2016

Reagent and Materials
All chemicals were of analytical grade, and double distilled water was used throughout the
experiments.Venlafaxine hydrochloride was obtained from Sigma Co. Pharmaceutical formula (Efexor-
XR), 75mgvenlafaxine hydrochloride in each capsulewas obtained from localdrug stores.Membrane
components silicomolybdic acid (SMA) H4SiO4.12MoO3. H2O and dioctylphthalate (DOP) C24H38O4 were
obtained from Sigma-Aldrich. High molecular weight poly(vinyl chloride) (PVC), used as the electrode
membrane material, and freshly distilled tetrahydrofuran (THF), used as a solvent for the membrane
components, were obtained from Fluka. Stock venlafaxine hydrochloride solution (10-2mol/L) was
prepared daily by dissolving an appropriate amount of the drug in double distilled water. Moredilute
solutions were prepared by appropriate dilution.
Preparation of Sensing Element
Sensing element used in electrode was an ion-pair complex composed of venlafaxine-silicomolybdate
(VE-SMA). VE-SMA was prepared by mixing about 50 mL of 1.0×10-2mol/L solution of venlafaxine
hydrochloride with 50 mL of 1.0×10-2mol/L solution silico molybdic acid (SMA). The resulting precipitate
was then filtered, washed with water and dried in room temperature for 2 days.
Preparation of PVC Membrane Electrode
Several membranes of different compositions as indicated inTable 1 were investigated. For preparation of
PVC membrane, different amounts of ion-pair with appropriate amounts of PVC, plasticizer and additive
were dissolved in tetrahydrofuran (THF), and the solution was mixed well into a glass dish of 5 cm
diameter. Then THF was evaporated slowly until an oily concentrated mixture was obtained. A glass tube
(7 mm in diameter) was dipped into the mixture for about 10 s so a transparent membrane of about 0.3
mm in thickness was formed. The tube was then pulled out from the mixture and kept at room
temperature for about 12 h. Afterwards, the tube was filled with an internal filling solution (1.0×10-
2mol/L NaCl and 10 2mol/L VE). The electrode was finally conditioned for 2 h by soaking in 10 3mol/L VE

Table 1.
Composition of different VE-SMA membranes and slopes of the corresponding calibration graphs
at 25.0 °C. Composition % (w/w) Linear range Ion Pair
1.0×10-5- 1.0×10-2 6.0×10-5- 1.0×10-2 3.6×10-6- 1.0×10-2 1.0×10-6- 1.0×10-2 7.4×10-4- 1.0×10-2 a Relative standard deviation (three determinations)
Construction of the Calibration Graphs
Potentiometric measurements were carried out with an Orion (Cambridge, MA, USA) Model 701 A digital
pH/mV-meter. Electromotive force (e.m.f) measurements were performed using the cellassembly:
Ag/AgCl/internal solution/PVC membrane/ test solution/SCE
Suitable increments of standard drug solution were add to 50.0 ml doubly distilled water so as to cover the concentration range from 1.0× 10 6 - 1.0× 10 2 mol L. In this solution the sensor and reference electrode were immersed and the e.m.f values were recorded after each addition. The electrode was washed with double distilled water and dried between measurements. The electrode potential was plotted versus negative logarithmic concentration of VE ( ), Slopes of the resulting calibration curves were calculated.
Analysis of Efexor- XR Capsule
The content of 10 capsules equivalent to 750mg of VE was transferred to a beaker and diluted to 50 ml
with bidistilled water. The mixture was filtered through a filter paper and washed with water. The filtrate
and washings were collected in a 100-ml standard volumetric flask and diluted to volume with bidistilled
Standard Addition Method
BEPLS Vol 5 [6] May 2016
The standard addition method [12] was applied, in which small increments of a standard VE solution 1 × 10 2 M were added to 50 ml aliquot samples of various drug concentrations. The change in potential reading at a constant temperature of 25˚C was recorded for each increment and used to calculate the concentration of the drug sample solution using the following equation: eq. (1)
where Cx and Vx are the concentration and volume of the unknown, respectively, Cs and Vs are the
concentration and volume of the standard, respectively, S is the slope of the calibration graph, and ΔE is
the change in potential due to the addition of the standards.

Potentiometric Titration of VE
An aliquot of VE solution was pipetted into a 100-ml titration vessel and the solution was diluted to 50 ml
with bidistilled water. The resulting solution was titrated with 1.0×10-3mol/L SMA solution and the
change of the cell potential upon addition of SMA was recorded. The volume of the titrant at the end point
was obtained using the first derivative.


Optimization of the Electrode
Influence of membrane composition
Several membranes of the different compositions were prepared. The slope and the working
concentration range for the different membrane composition are given in Table 1. The best performance
was exhibited by membrane D with VE-SMA,DOP and PVC in the ratio 8:46:46, respectively. This
membrane showed a nearly Nernestian response with slope of 58.8 mV/decade and a linear
concentration range 1.0×10 5–1.0×10 2mol/L (Figure 2).
Figure 2. Typical calibration graph of VE-SMA–PVC membrane electrode

Response Time
The response time is the time which elapses between the instant when an ion-selective electrode and a
reference electrode (ISE cell) are brought into contact with a sample solution. The response time was
tested for 1.0 × 10 -6 - 1.0 × 10-2mol L VE solutions. This electrode exhibitsa fast dynamic response of
about 20-35 s over the whole concentration range of VE drug. The electrode was used over a period of 5
weeks without any significant change in potential
Effect of pH
The effect of pH of the VE solutions (1.0 10-3and 1.0 10-5mol L VE) on the electrode potential was
investigated. Aliquots of VE drug ( 50 mL ) were transferred to 100 mL beaker and the tested ion-
selective electrode in conjugation with a saturated calomel electrode and a combined glass electrode
were immersed in the same solution. The solutions were acidified by the addition of very small volumes
of 0.1 M HCl acid then the pH value was increased gradually using NaOH (0.1 or 1.0 M) for each pH value,
the potential readings corresponding to different pH values were recorded and thus the potential-pH
curves were constructed as shown in Figure 3 . As is obvious, within the pH range 3.0–8.0 the electrode
BEPLS Vol 5 [6] May 2016

potential is practically independent of pH, and in this range, the electrode can be safely used for venlafaxine HCl determination. Figure 3.Effect of pH on electrode potential/mV of VE-SMA–PVC membrane electrode.

Selectivity coefficients for different ions with respect to venlafaxineHCl were determined by the activity
ratio method [13], in which the selectivity coefficient is measured as the ratio of ion activities or
concentrations that generate the same membrane potential when measured in a separate solution type
experiment. A venlafaxineHCl calibration graph carried out in water was used to calculate the
concentration of venlafaxine HCl (CVE) that corresponds to the potential observed for a certain
concentration (Cj) of interfering ion. The selectivity coefficients were calculated as the ratio of these
eq. (2)
Where j is the interfering ion. The resulting selectivity coefficients are shown in Table 2. In the case of glucose and lactose, the high selectivity may be attributed to the difference in polarity and to the lipophilic nature of their molecules relative to VE cation. When the concentration of these species was substantially increased, the potential decreased (i.e. it provided negative interference). Table 2. Selectivity factor values
the proposed electrode at 25.0 Interfering ions
log K VE , J
The proposed membrane sensor was proved to be useful in the potentiometric determination of VE drug
in pure solutions and in capsules (Efexor- XR,75mg),by both the standard addition and the potentiometric
titration methods. Five replicate determinations at different concentration levels were carried out using
the studied electrode to test the precision of the method. The result are shown in Tables 3 and 4. The
standard deviations were found to be ≤1.5, indicating reasonable repeatability and reproducibility of the
selected method.
To compare the proposed method to a reported method, VE in Efexor-XR capsules was assayed by HPLC
[14].The results are in good agreement with those obtained from the reported method .The results were
illustrated in Table 4 and the average recovery was between 99.81% and 100.76%. HPLC31 was also
performed as comparative method. It was found that the results from the determination of venlafaxine
BEPLS Vol 5 [6] May 2016
hydrochloride using this method were almost the same as those from HPLC. Thus, this method was suitable to detect venlafaxine hydrochloride in capsules . Table 3. Test of precision of the standard addition and potentiometric titration methods on pure
venlafaxine hydrochloride. Standard addition
Potentiometric titration
Amount taken
Recovery %
Recovery %
Mean ± SD
Table 4. Standard additions and potentiometric titration methods for determination of VE in Efexor-XR
Proposed methods Standard
Amount taken (mol L) Recovery % RSD* Recovery %

* RSD (Five determination)

The proposed electrode is sufficiently simple and selective for the determination of VE in pure form and
in capsules. The electrode showed a very good selectivity to VE in the presence of various common
inorganic cations, sugars and amino acids. Thus, this electrode can be used as alternative analytical tools
to spectrophotometric and chromatographic methods, for the determination of this drug in bulk powder,
pharmaceutical preparations


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London, 2005; pp 447. 2. M. S. Holliday and P. Benfield, Drugs, 49:2(1995) 280. 3. B. K. Madras, Z. Xie, Z. Lin, A. Jassen, H. Panas, L. Lynch, R. Johnson,E. Livni, T.J. Spencer, A.A. Bonab, MillerGM and. A. Fischman, J PharmacolExpTher.,319:2 (2006) 561. 4. B.B. Raut, B.L. Kolte, A. A. Deo, M. A. BagoolandD.B. Shinde, J LiqChromatogrTechnol., 26: 8(2003) 1297. 5. E. B. Asafu-Adjaye,P. J. Faustino, M. A. Tawakkul, L.W. Anderson, L. X. Yu andH. Kwon, J. Pharm. Biomed. Anal.,47:5(2007)1854. 6. N. C. Purdel, D. Balalau, M. Ilie and C. C. Arama, Farmacia.,58:1( 2010) 62.
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Lamia A. Al-bedair. Ion-selective Electrode Determination of Venlafaxine Hydrochloride in pure form and Capsules .
Bull. Env. Pharmacol. Life Sci., Vol 5 [6] May 2016: 48-52
BEPLS Vol 5 [6] May 2016

Source: http://bepls.com/beplsmay2016/9.pdf

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Dear CM/PLM Professional, Please find enclosed DSD's newsletter, addressing news in CM, PLM, ERP and Process Improvements that we thought might interest you. We would appreciate receiving comments and suggestions to make this newsletter more helpful and interesting. We encourage you to send us news you hear that might be of interest to others of the CM community. Subscription to this newsletter is free-of-charge. To subscribe to our mailing list please send us an e-mail with SUBSCRIBE in the subject. If you do not want to receive further issues please send us an e-mail with REMOVE in the subject. CAD AND DESIGN TOOLS 1. ANSYS Reports First Quarter 2016 Financial Results ANSYS, Inc. today announced its financial results for the first quarter of 2016. The Company reported GAAP and non-GAAP revenue growth in constant currency of 6% and 5%, respectively, and GAAP and non-GAAP diluted earnings per share of $0.63 and $0.77, respectively, for the quarter. Recurring revenue, which is comprised of lease license and maintenance revenue, totaled 78% of revenue for the first quarter . 2. Gerber Technology's Digital Solution Links Data, Smart Machines to Drive Mass Production and Mass Customization Gerber Technology is showcasing its Digital Solution at the Texprocess Americas show in Atlanta. Apparel and industrial companies are under significant competitive pressures to design, develop and produce their products faster and more efficiently while ensuring they get the right products to market at the right time and at the right price. Whether producing volume for the masses or customizing small lots, companies are struggling because of an inability to move data from process to process and machine to machine. At Texprocess, Gerber will demonstrate each step of its Digital Solution to illustrate how companies can network their software and smart machines to form an end-to-end solution to help meet the workflow challenges of mass production and mass customization. 3. FARO Reports First Quarter 2016 Financial Results FARO Technologies, Inc. (FARO) today announced its financial results for the first quarter ended March 31, 2016. Sales for the quarter ended March 31, 2016 were $75.7 million, up 8.3% compared with $69.9 million in the first quarter last year. Excluding approximately $0.9 million of unfavorable foreign exchange impacts, first quarter sales would have increased approximately 10% as compared with the first quarter of 2015. The Company's sales growth was driven primarily by higher metrology sales within the Americas and Asia-Pacific regions. Gross margin for the quarter was 56.3% compared with 56.6% in the prior year period with product and service margins remaining relatively consistent with the prior year period. Operating income for the quarter was $4.3 million compared with $1.9 million in the prior year period, reflecting increased sales volume partially offset by a modest increase in operating expenses. 4. Cadence Expands OrCAD Solution to Address Flex and Rigid-Flex Design Challenges for IoT, Wearables and Mobile Devices Today at CDNLive EMEA, Cadence Design Systems, Inc. announced the OrCAD 17.2-2016 release with new capabilities for OrCAD® Capture, PSpice® Designer and PCB Designer that address challenges with flex and rigid-flex design as well as mixed-signal simulation complexities


Special Expanded Issue • Exercise to Improve Mobility Published by the Multiple Sclerosis Symptom Management Update Association of AmericaDouglas G. Franklin By Diana M. Schneider, Ph.D . 3 This expanded cover story gives an overview Gary Wallace, CPA of the strategies and agents used to manage