Jordan Journal of Chemistry Vol. 6 No.4, 2011, pp. 423-437
423
JJC
Novel PVC Membrane Selective Electrode for the Determination of Etoricoxib in Pharmaceutical Preparations
Salwa Rassia*,Basher Eliasa, Mohammed Samer Bassmajeib
a Department of Chemistry, Faculty of Sciences, University of Al-Baath, Homs, Syria. b Department of Chemistry, Faculty of Sciences, University of Aleppo, Aleppo, Syria. Received on June 26, 2011 Accepted on Oct. 11, 2011
Abstract The construction and general performance characteristics of novel potentiometric
membrane sensors responsive to the etoricoxib are described. The sensors are based on the
use of ion-pair complex of etoricoxib (ET) with Picric Acid Pc-H (ET- Pc-H) as exchange sites in
a with different plasticizers dibutyl phthalate (DBP) (electrode B) tri-n-butyl phosphate (TBP)
(electrode C), or dioctylphthalate (DOP) (electrode A). The electrodes show a fast, stable and
near- Nernstian for the mono charge cation of ET over the concentration range 0.09 - 42.96 mM
at 25 ˚C over the pH range 5-14 with cationic slope of 56.8 ± 0.5 and 55.0 ± 0.5 per
concentration decade for ET-B and ET-A electrodes respectively. The lower detection limit is
0.05 mM and 0.07 mM with the response time 15s in the same order of both electrodes.
Selectivity coefficients of ET related to a number of interfering cations and some organic
compounds were investigated. There are negligible interference caused by most of the
investigated species. The direct determination of 0.5 - 20 mM of ET shows an average recovery
of 99.62 - 102.40% and 100.27-102.61 a mean relative standard deviation 2.75-0.64 and 1.76-
0.41 for A and B electrodes respectively. The results obtained by determination of ET in tablets
using the proposed electrodes which comparable favorably with those obtained by
spectrophotometric method. Validation of the method shows the suitability of the electrodes for
the determination of ET in pharmaceutical formulations.
Keywords: Etoricoxib; Picric acid; PVC membrane; Potentiometry; Method validation.
Introduction Etoricoxib (Figure1.) is a member of a new class of agents called Coxibs. is a
novel orally active agent that selectively inhibits cyclooxygenase-2 (COX-2)[1].
Chemically it is 5-chloro-2-(6-methyl pyridin-3-yl)-3-(4-methylsulfonylphenyl) pyridine[2].
It is used as a non-steroidal anti-inflammatory agent [3]. It has selective inhibition of
COX-2 that decreases GI toxicity and without effects on platelet function [4] It is
commonly used for osteoarthritis, rheumatoid arthritis, post operative dental pain and
acute gout chronic musculoskeletal pain postoperative dental pain and primary
dysmenorrheal [5]
Etoricoxib The therapeutic importance of this drug has prompted the
development of many methods for its assay. The drug is available in tablet dosage * Corresponding author: Tel: 00963-966-243153; e-mail: [email protected].
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form and is not yet official in any of the pharmacopoeias. Several methods have been
reported for the analysis of etoricoxib in pharmaceutical dosage form as well as in the
biological fluids and tissues, spetrophotometric methods [6-10]. chromatographic
methods HPLC [11-15], High-performance thin-layer chromatography [16]. LC/Mass
spectrophotometry [17-20] and RP-HPLC method [21] for the estimation of etoricoxib
Etoricoxib has been determined in biological samples by High Performance
Liquid Chromatography[22-23], Reverse Phase High Performance Liquid Chromatogra-
phic[24]. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) [25]. A liquid
chromatography-tandem mass spectrometry method with atmospheric pressure
chemical ionization (LC-APCI/MS/MS) [26].
Some of these methods require expensive equipments and or special treatment.
Potentiometric membrane sensors have been more extensively used in
pharmaceutical analysis. Their advantages are simple design, low cost, adequate
selectivity, low detection limit, high accuracy, wide concentration range, turbid solution
and have found wide applications in divers field of analysis [27-30]. To our knowledge no
potentiometric electrochemical sensors has been yet described for determination of ET
the present work describes the construction and evaluation of novel PVC membrane
sensors for ET in its pharmaceutical preparations. The sensitivity and stability offered
by the PVC sensors are in advantageous to allow accurate determination of low levels
of ET
Figure 1: Chemical structure of etoricoxib
Experimental Apparatus
Potentiometric and pH measurements were carried out using a digital Shott
Gerate pH meter, supplied by Consort C 830 (Belgium) with a combination glass pH
electrode. A water bath shaker (Grant instruments, Cambridge Ltd, England) was used
to control the temperature of the test solutions. A saturated calomel electrode (SCE)
was used as the external reference electrode (Mettler, Switzerland) while an Ag/AgCl
electrode was used as an internal reference the electrochemical system may be
represented as: Ag/AgCl / inner solution / membrane/ test solution // KCl salt bridge //
saturated calomel electrode. NMR Spectrometry Bruker ,400MHz. FT/IR 4100(Fourier
transform infrared spectrometer) Jasco
N
N CH3
SCH3
O
O
Cl
425
All emf. measurements were performed at room temperature using the cell
assembly: Ag/AgCl | inner solution| PVC membrane |test solution ||KCl salt bridge||
Hg/HgCl2(sat.)
Reagents and solutions
All of the chemicals used were of analytical grade. Doubly distilled water was
used to prepare all solutions. High-molecular-weight poly (vinyl chloride) (PVC) was
from SABIC.Co., dioctyl phthalate 98.9% (DOP), tri-n-butyl phosphate 97% (TBP), and
di-n-butyl phthalate 99% (DBP) were obtained from BDH.Co.,England.,tetrahydrofuran
(THF) was obtained from Merck.
Pure-grade Etoricoxib (C18H15 Cl N2O2S, 358.84 g mole-1) was supplied by Aarti
Drugs Limited (India). Its purity was found to be 99.95% according to the compendia
method. Pc-H (C6H3N3O7 229.10g.mol–1) was obtained from Merck
Formulations
Etoxia tablets supplied by Razi Pharmaceutical Industries (Aleppo, Syria), each
tablet was labeled to contain Etoricoxib 120, 90, 60 mg /tab.
A stock solution of 50mM ET was prepared by dissolving an appropriate amount
(1.7942 g) of the compound in 50ml methanol and making the solution up to 100mL
with doubly distilled water. Standard ET solutions (0.05- 45mM) were prepared daily by
sequential dilution of the appropriate stock solutions with the blank solution. The
solution of 10mM Pc-H was prepared by dissolving appropriate amount of the
compound in the methanol. ET and Pc-H stock solutions were stored in dark at
refrigerator. Stock solutions of 1M for each of LiCl, NaCl, KCl, NH4Cl, CaCl2, MgCl2,
BaCl2, ZnCl2, MnSO4, Ni(NO3)2, Co(NO3)2, Cu(NO3)2, Pb(NO3)2, FeCl3, AlCl3, CrCl3,
glucose, fructose, lactose, starch, micro crystalline cellulose, carboxymethyl cellulose,
polyethylene glycol, titanium dioxide, and polysorbate 80 were prepared by dissolving
the appropriate amount of the compounds. More diluted solutions were prepared by
subsequent dilutions of the stock solutions.
Sample preparation
The homogenized powder was prepared from ten accurately weighed ET
tablets. An appropriate amount of this powder was dissolved in methanol and doubly
distilled water. Dissolution of the drug was assisted by means of a magnetic stirrer.
The mixture was then filtered and mad up to the mark in a 100- mL volumetric flask.
Different volumes of the stock solution were taken and subjected to the direct and
standard –addition methods.
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Preparation of ion-pair compound
Ion-pair (ET+Pc-) was prepared by mixing equal volumes of 10-2 M methanolic
solutions of ET and Pc-H under stirring The precipitate resulted after the evaporation
methanol. The obtained precipitate was filtered, washed thoroughly with doubly
distilled water to remove any non-complex material, dried at room temperature and
ground to a fine powder in a mortar. The melting point of obtained ion-pair complexes
were: 205–210°C .
So, the composition of the ion pair complex was confirmed by NMR and IR
spectrophotometer to be 1:1 (ET: Pc). The ionic pond is set up between amine group
at ET cation and hydroxyl group at Pc anion, as shown at (Figure 2).
Figure 2: Etoricoxib- Picric Acid (ET-PC) complex structure and fully optimized
structure of complex
Construction of etoricoxib membrane electrodes
The electrodes were constructed according to the method of Craggs [31]. The
membrane composition was studied by varying the percentages (w/w) of the ion-pair
complex, PVC and DOP (electrode A), DBP (electrode B), or TPP (electrode C) as
plasticizing solvent mediators. until the optimum composition exhibiting the best linear
responses was obtained. The membranes were prepared by dissolving the required
amount of ion pair complex, PVC and DOP, DBP or TPP in THF. The homogeneous
mixtures were poured into glass Petri dishes (8 cm diameter), and were then covered
with a glass plates, and allowed to evaporate overnight at room temperature. The
thickness of obtained membrane was about 0.15mm. Membranes (12mm diameter)
were cut out and glued using PVC-THF paste to the polished end of a plastic cap
attached to a glass tube. The electrodes bodies was filled with a solution of 1×10-1M
KCl and 1×10-3M ET as the inner electrolyte, and Ag/AgCl was diped in it as internal
reference electrode. The electrode potential was measured against the SCE as the
reference electrode. Initially, the membrane electrodes were conditioned by soaking
into 25mM of ET solution for 5 hour. When off-use, the electrodes were stored in air.
O
N
+NH
CH3
SCH3
O
O
Cl
N+
O
O-N+
O
-O
N+
O O-
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Selectivity of sensors
The potentiometric selectivity coefficient K , of an ISE commonly used as
quantitative expression of the ability of the electrode to respond primarily to the analyte
ion in the presence of interfering ions. The influence of the presence of some different
species on the response of ET electrodes was investigated. The selectivity coefficient
K , of the proposed electrodes were calculated in the presence of related organic and
inorganic substances using Matched Potential Method (MPM) [32-33]. The selectivity
coefficient K , measured by Matched Potential method was calculated from the
following equation:
K , a′A-aA)/aB (1)
Where a′A known activity of primary ion, aA fixed activity of primary ion and aB
activity of an interfering ion.
The electrode shows interferences from ions when the value 1⟩potABK , Ions do
not interfere in the electrode response when the value potABK⟩1
General procedure
The performance of the three electrodes obtained was investigated by
measuring e.m.f. values of 0.05 - 45 mM of ET. The electrodes were calibrated by
added volumes of 50mM working solution of ET successively in 50 ml of water to
generate a total concentration ranging from 0.05 - 45 mM ET, followed by immersing
the ET-electrode, together with a calomel reference electrode in the solution. the
potential reading were recorded after stabilization, and the e.m.f was plotted as a
function of the logarithm of the ET concentration. The calibration graph was used for
subsequent determinations of unknown ET concentrations.
Potentiometric determination of ET.
ET has been determined potentionmetrically using the investigated electrode by
the Direct method and by standard addition method [34-35]. In this method the
proposed electrodes (A,B) (ET-Pc) was immersed into a sample of 15 ml with an
unknown concentration of a ET solution, and the equilibrium potential of Eu was
recorded. Then 1 ml of 50mM of standard ET was added into the testing solution and
the equilibrium potential of Es was obtained. From the potential change, ∆E= Eu- Es, we
could determine the concentration of the test sample using the equation:
CX =CsVs/[(Vx+Vs)×10 ∆E/S-Vx ] (2)
Where Cx and Vx are the concentration and the volume of an unknown sample,
Cs and Vs are the concentration and the volume of the standard, respectively S is the
slope of the calibration graph (mV decade-1), and ∆E is the change in the potential
(mV). The standard addition method was applied for the determination of ET in
commercial preparations.
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Results and Discussion Composition of the electrode
The membrane composition was studied by varying the percentages (w/w) of
the ion pair complex (ET-Pc) and plasticizer and PVC. Until the optimum composition
exhibiting the best linear responses was obtained. This composition is given in table 1.
Eight membrane compositions were investigated. The results showed that the
electrode made by membrane (III) with 3% ET-Pc ion-pair complex exhibited the best
performance characteristics (slope 56.75mV decade-1,at 25ºC; linear range (0.07-
42.96 mM ET), and response time 15 s. The other membranes exhibit slopes ranging
between 46.29 and 54.69 mV dcade-1. In all subsequent studies, electrode made of
membrane III were used. For all construted electrodes, the percentage of ion- pair
ranging between 1-8% was found to offer better slopes and correlation coefficients.
The results obtained with ion-pair for the three plasticizers are summarized in table 2.
The electrodes A and B exhibit comparable linear ranges and the lowest detection limit
than electrode C.
The influence of internal solution
The proposed selective electrode was also examined at different concentrations
of the inner reference solution. The concentration of the internal solution of ET in the
electrode was changed from 0.01-10 mM and the potential response of the electrode
was measured. It was found that variation of the concentration of the internal solution
does not cause any significant difference in the potential response of the electrode. A
1mM concentration of ET as internal solution was quite appropriate for proper
functioning of the electrode.
Table.1: Optimization of the Membrane Ingredients
composition,%(w/w)
Membrane Ion Pair Complex
PVC DBP Slop mVdecade-1 Detection limit mM
I 1 49.5 49.5 53.14 0.072
II 2 49.0 49.0 54.69 0.060
III 3 48.5 48.5 56.75 0.054
IV 4 48.0 48.0 51.84 0.080
V 5 47.5 47.5 50.23 0.098
VI 6 47.0 47.0 49.87 0.100
VII 7 46.5 46.5 48.33 0.140
VIII 8 46.0 46.0 46.29 0.180
Plasticizer selection
(ET-Pc) was a stable water insoluble ion-pair complex though readily soluble
organic solvents such as THF, etc. The complex was incorporated into a PVC
membrane with the following plasticizers: DOP (electrode A), DBP (electrode B), and
TBP (electrode C). The working characteristics for the electrodes were assessed on
429
the basis of their calibration curves. The physical properties of these membranes were
as follows: white, flexible, clear, and transparent (non-crystalline). Non-nernstian slope
was obtained for electrode based on TBP The slope is 47.49 mV/decade. with
correlation coefficient 0.979 .The linear range for electrode was 0.2-34.70 mM with
detection limits of 0.1 mM. Near Nernstian slopes were obtained for the electrodes
based on DOP and DBP (electrode A and B). gave a slope of 55.00 and 56.75 mV
decade-1 with a correlation coefficient of 0.999 and 0.999 and a linear concentration
range 0.09-41.29 mM, and 0.07-42.96 mM a detection limit 0.07 and 0.05 mM
respectively.
The TBP which has a low viscosity (3.11 cSt), leads to leaching of the complex
from the membrane or may have a high stereo effect on methyl groups. All further
studies were conducted using DOP and DBP as the plasticizers.
Effect of soaking
Freshly prepared electrodes must be soaked to activate the surface of the
membrane to form an infinitesimally thin layer for ion-exchange process to occur [36].
This preconditioning process requires different times, depending on the diffusion and
equilibration at the electrode test solution interface. A fast establishment of equilibrium
is certainly a condition for a fast potential response. Thus, the performance
characteristic of the ET electrode was investigated as a function of the soaking time.
For this purpose the electrode was soaked in a 30 mM solution of ET, Pc-H and water
at room temperature. The optimum soaking time and the optimum solution was found
to be 5 h.for 30mM solution of ET. During this period, the sensors were washed with
water after each application and kept dry in air at room temperature When off-use. The
results indicate that during the 5h of soaking the slope remains constant at about 56.75
mV decad-1, at 25ºC. (E, mV vs. t, min) plots (Figure 3) were obtained after the
electrode was soaked continuously in 30 mM ET, water and Pc-H for 30-700 min.
Figure 3: Effect of stock solution on response electrode
0
5
10
15
20
25
0 200 400 600 800
E,mV
t,min
waterETPc H
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Table 2: Effect of the nature of an ion –pair and a plasticizer on characteristics of the
electrodes
C B A Electrode
8% 3% 5% Ion-pair complex TBP DBP DOP Plasticizer 47.49 56.75 55.00 Slope mVdecade-1
0.20-34.70 0.07- 42.96 0.09-41.29 Linear range,mM
0.979 0.999 0.999 Correlation coefficient 0.10 0.05 0.07 Detection limit, mM
Optimization of pH
The influence of pH of the test solution on the potential response of the
membrane for (0.5, 5, 15, 30 mM) ET solution was tested by following the potential
variation in the pH range 1-14. The electrode response for different ET concentration
was tested at various pH values, each time being adjusted by using hydrochloride acid
or sodium hydroxide solution. Potential -pH plots the results are given in (Figure 4) As
is obvious, the mrmbrane electrode could be suitably within the pH rang 5-12, the
potentials remain constant did not vary by more than, ±0.5mv. At lower pH (pH <5)
values the potential decrease may be due to the interference of hydronium ion and the
penetration of H3O+ into the membrane surface, or a gradual increase of the
protonated species [37-38].
Figure 4: Effect of the pH on the response of the electrode
-80
-60
-40
-20
0
20
40
60
0 5 10 15
E,mV
pH
0.5mM
5mM
15mM
30mM
431
Effect of the temperature of the test solution
The Effect of the temperature of the test solution on the potential response of
the membrane was tested by following the slopes variation in the temperature range
20-65ºC (Figure 5) The results show that within the temperature range investigated the
electrode responds practically to the ET concentration with a slopes between 56.42-
53.02 mV.decad–1. and usable concentration range of about 0.07-42.96 Mm.
Figure 5: Effect of the temperature of the test solution on the potential response of the
membrane
Calibration graphs
Using the optimized membrane composition and conditions described above,
the potentiometric response of the electrode was studied based on the ET
concentration in the range of 0.01- 45 mM. The calibration curves for the electrodes A
and B containing DOP or DBP as plasticizer gave an excellent linear response from
0.07– 42.96 mM, as shown in figure 6. The results given in table 3 show the
characteristics of performance of the membrane electrodes. The least squares
equation obtained from the calibration data is as follows:
E(mV)=S×log([ET,M]+intercept
where E is the potential and S the slope of the electrodes.
52
53
54
55
56
57
15 25 35 45 55 65
slop
e
T,˚C
432
Figure 6: Calibration graph of ET membrane electrode.
Response time
Response time is an important factor an ion-selective electrode (ISE). The time
required for the electrodes to reach steady potential values, after immersion of the
electrode in different concentration ranging from 0.08, 0.4, 4 and 40.mM of ET solution
was studied. The average time was found to be short, ranging from 15 s for
concentration 0.4, 4, 40 m M solution. the longer response time reached around 20s at
0.08 mM. The electrodes gave the same range of response times. These values
indicate the high stability of the electrodes during the measurements. A typical plot for
response time is shown in figure 7 for the electrode based on DBP as the plasticizer.
Figure 7: Plot the response time of DBP electrode
Lifetime
The electrode lifetime was investigated by making calibration curves and
periodically testing a standard solution of 0.07- 42.96 mM of ET, and calculating to
response slope electrode B, was found to have an operative life of more than 50 days,
with the slope ranging from 56.75 to 57.15 mV decade-1 and a linear concentration
range from 0.07-42.96 mM. Electrode A exhibited good stability in terms of slopes of
55.00 to 56.04. mV decade-1 in the linear domain of concentration from 0.09-41.29
y = ‐55.007x + 123.21R² = 0.9993
-120.0
-90.0
-60.0
-30.0
0.0
30.0
60.0
1.02.03.04.05.0
E,mV
Pc
DOPy = ‐56.757x + 126.98
R² = 0.9996
-120.0
-90.0
-60.0
-30.0
0.0
30.0
60.0
1.02.03.04.05.0
E,mV
pc
DBP
-140
-105
-70
-35
0
35
70
0 15 30 45 60 75 90 105 120 135 150
E,mV
t,min
0.08mM
0.4mM
4mM
40mM
433
mM. This electrode can be used continuously for about 43 days. Two changes were
observed. Firstly, a slight gradual decrease in the slope (from 56.75 to 54.63mV
decade-1) was found, and secondly an increase in the detection limit (from 0.05 to 0.08
mM) was noted. However, the electrode with DBP as plasticizers could be used for
about 50 days without any considerable decrease in the slope value.
Table 3: Response characteristics of membrane electrodes
Electrode number A B
Plasticizer DOP DBP
Parameter Slope mV/decad-1 55.00 56.75
Correlation cofficient 0.999 0.999
Linearity range (mM) 0.09-41.29 0.07-42.96
Lower detection limit(mM) 0.07 0.05
Response time(s) t ≥ 15 t ≥15
Working pH range 5-14 5-14
Temperature ºC 25 25
Life time(day) 43 50
Selectivity of electrode
The influence of some inorganic cations such as of Li+, Na+, K+, Ca2+, Zn2+, Ba2+,
Mn2+, Mg2+, Ni2+, NH4+, Cu2+ pb2+, CO2+, Fe3+, Al3+, Cr3+, sugars (glucose, fructose) and
excipients on the electrode response was investigated. The selectivity of the electrode
was measured by applying the matched Potential method (MPM). According to this
method, the activity of ET was increased from aA = 10 m M (reference solution) to
a′A=10.12 mM, and the changes in potential (∆E) corresponding to this increase were
measured. Next, a solution of an interfering ion of concentration aB is added to a new
10 mM reference solution until the same potential change (∆E) was recorded. The
selectivity factor, , , for each interferent was calculated using equation (1). The
results are given in table 4. Results reveal reasonable selectivity for ET in presence of
many related substances. The selectivity coefficient obtained by this method showed
that there are no significant interferences from the cations, this reflects avery high
selectivity of the investigated electrode towards ET. The inorganic cations do not
interfere owing to the differences in the ionic size, and consequently their mobilities
and permeabilities as compared with ET. The selectivity of the electrode towards
neutral sugars was evaluated. The tolerance was considered as the concentration
imparting a ± 0.2 mV drift in the potential reading. The results indicate that glucose,
fructose, lactose and starch do not interfere respectively. The experiments showed no
interference with respect to ET response for electrodes A and B.
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Table 4: Selectivity coefficients for of the ET-Pc responsive electrode.
, Foreign , Foreign
6.81×10-5
6.67×10-5
1.22×10-5
8.9×10-5
4.0×10-5
5.5×10-5
2.3×10-5
9.0×10-4
2.2×10-5
5.2×10-6
9.8×10-5
7.6×10-6
Cd+2
Cr+3
Fe+3
Glucose
Fructose
Lactose
starch
Microcrystalline cellulose
Carboxy metyle cellulose
polyethylene glycol
titanium dioxide
polysorbate 80
1.20×10-4
1.42×10-4
3.09×10-4
4.86×10-4
4.25×10-5
8.05×10-5
5.10×10-5
3.14×10-5
6.13×10-5
7.81×10-5
5.69×10-5
8.52×10-5
Li+1
K+1
Na+1
NH4+
Mg+2
Mn+2
Ca+2
Ba+2
Ni+2
Cu+2
Zn+2
pb+2
Validity of the proposed method
The accuracy and precision of the proposed methods were carried out by four
determination at four different concentrations using both direct and standard-addition
methods. The precision and accuracy of the method expressed as coefficient of
variation as precision and percent deviation of the measured concentration
(recovery %) as accuracy. The results obtained are within the acceptance
range. average recovery of (99.62 -102.40) and (99.75.27-102.61)%,
coefficient of variation (2.82-0.43 )and (2.13-0.41)% and (Analytical Standard
Error of the Mean (ASE) (0.008-0.013) and (0.005-0.012)% respectively for
sensor-A and B and for tow methods. Table 5 shows the values(RSD%) ,(R%)
and (ASE) for different concentrations of the ET determined from the
calibration curves and by using standard-addition methods. These accuracy
and precision show that the electrode B has a good repeatability and
reproducibility. The proposed electrode were found to be selective for the
estimation of ET in the presence of various tablet excipients. For this purpose, a
powder blend using typical tablet excipients was prepared along with the drug and then
analyzed. The recoveries were not affected by the excipients and the excipients blend
did not show any interference in the range of analysis correction was used. The results
in table 5 showed that the electrode based on DBP as a plasticizer was the best
electrode in analysis of the tablets of ET, since electrode has RSD (1.76-0.41) for a
concentration of (0.5-20 mM) by direct method indicating that it has better precision
than electrode A RSD (2.75-0.64). Electrode based on DBP as a plasticizer were the
best electrodes in analyses of the tablets.
435
Table 5: Accuracy and precision for the determination of ET using the proposed PVC
membrane sensors. in pure solution
Elec
trod
e Direct method standard-addition method
TakenmM
Found mM
RSD%
R% TakenmM
FoundmM
RSD%
R%
A
0.5 0.512 2.75 102.40 0.2 0.201 2.82 100.50
2.0 1.995 1.10 99.75 0.4 0.401 1.66 100.25
5.0 5.019 1.05 100.38 0.8 0.814 1.47 101.75
10.0 10.084 0.84 100.84 1.0 1.013 0.77 101.30
20.0 19.925 0.64 99.62 1.5 1.509 0.43 100.60
B
0.5 0.513 1.76 102.61 0.2 0.198 2.13 99.00
2.0 2.033 1.02 101.65 0.4 0.399 1.28 99.75
5.0 5.031 0.85 100.62 0.8 0.812 1.07 101.50
10.0 10.027 0.62 100.27 1.0 1.011 0.75 101.01
20.0 20.259 0.41 101.29 1.5 1.512 0.42 100.80
Average of four determinations
Analytical application
The ET membrane electrodes were used for the determination of ET in
pharmaceutical preparations using both direct and standard-addition methods. The
direct method is the simplest for obtaining quantitative results. A calibration graph was
constructed and concentration of the unknown was calculated from the linear equation
of the calibration curve. Direct determinations of ET in tablets were carried out using
the developed membrane electrodes. the results are summarized in table 6. The
content of drug in its formulation had good agreement with the declared amount. The
standard-addition method was applied by adding a small portion (1mL) of a 50mM
standard ET solution to 15mL of various formulation drug concentrations (60-90-120)
mgET/tablet, (0.167,0.251,0.335)mM. The change in the potential reading (at a
constant temperature of 25ºC) was recorded after each addition, and was used to
calculate the concentration of ET by the equation (2). Thus ,the determination of the
concentration depends mainly on ∆E; hence, to obtain a noticeable ∆E, are needed to
prepare a higher concentration of the standard. Results of the standard-addition
method are given in table 6.
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Table. 6: Determination of ET in its pharmaceutical preparation using the proposed electrode
Sample Nominal value
mgET/tablet Potentiometry
Direct Standard addition
Spectrophotometry
Etoxia 60
R%±SDa 101.06±0.40 100.45±0.50 99.73±0.31
t-Valueb 0.34 2.05 1.830
F-Valueb 1.66 2.60
Etoxia 90
R%±SDa 100.15±0.46 100.52±0.53 100.08±0.33
t-Valueb 0.76 2.14 0.57
F-Valueb 1.94 2.57
Etoxia 120
R%±SDa 100.31±0.77 100.44±0.63 100.46±0.49
t-Valueb 0.90 1.57 2.05
F-Valueb 2.46 1.65
a Five independent analyses.
b Theoretical values for t- and F-values at four degree of freedom and 95% confidence limit are (t=2.776) and
(F=6.26).
The determination of ET in tablet was carried out using the proposed electrode.
The results were compared to those obtained using the spectrophotometric method [8].
The determination of ET in its pharmaceutical formulations Etoxia gave an average
Recovery of (100.15-101.06) Mean values were obtained with a Student’s t- and F-
tests at 95% confidence limits for four degrees of freedom. as shown in Tab 6. The
data reveal that results favorably compare with those obtained by spectrophotometric.
The results show comparable accuracy (t-test) and precision (F-test), since the
calculated values of t-tests and F-tests were less than the theoretical data. value
indicating no significant difference was found between the two methods
Conclusion In conclusion, the developed PVC membrane sensors described in this work
offer a simple, accurate, selective, and specific tool for quantitative determination of ET
in some pharmaceutical formulations. The membrane sensor ET-Pc based on DBP
seem to be better than ET-Pc based on DOP with respect to calibration, slope, and
accuracy. The statistical evaluations of the proposed method in comparison with
spectrophotometric method indicate that the method is accurate and precise. The
proposed analytical method proved to be simple and rapid, with good accuracy
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