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: rassi.salwa@gmail.com.

424

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.

426

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-

427

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.

428

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

430

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.

434

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.

436

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

References [1] Riendeau, D.; Percival, M.D.; Brideau, C.; Charleson, S.; Ethier, D.; Dube, D.;

Falgueyret,J. P.; Friesen, R.W.; Gordon, R.; Greig, G.; Guay, J.; Mancini, J.; Ouellet, M.; Wong, E.; Xu, L.; Boyce, S.; Visco, D.; Girard, Y.; Prasit, P.; Zamboni, R.; Rodger, I.W.; Gresser, M.; Ford-Hutchinson, A.W.; Young, R.N.; Chan, C.C., J. Pharmacol. Exp. Ther., 2001, 296, 558–566.

437

[2] Gajraj, N. M., Anesth. Analg., 2003, 96, 1720-1738 [3] Sweetman, S. C. Ed., Roya Pharmaceutical Society of Great Britain, 2005, 38. [4] Agrawal, N. G.; Porras, A. G.; Mathews, C. Z.; Woolf, E. J.; Miller, J. L.; Mukhopadhyay,

S.; Neu, D. C.; Gottesdiener, K. M., J. Clin Pharmacol., 2001, 41, 1106-1110 [5] Cochrane, D. J.; Jarvis, B. G.; Keating, M., Etoricoxib Drugs, 2002, 62, 2637-2651. [6] Singh, R. M.; Kumar, Y.; Sharma, D. K.; Mathur, S. C.; Singh, G. N.; Ansari, T. A.; Jamil,

S., Indian. Drugs., 2005, 42, 355-536. [7] Shahi, S. R.; Agrawal, G. R.; Rathi, P. B.; Shinde, N. V.; Somani, V. G.; Mahamuni, S. B.;

Padalkar, A. N., RJC. Rasayan. J. Chem., 2008, 1, 390-394 [8] Shah, K.; Gupta, A.; Mishra, P., E. J. Chem., 2009, 6, 207-212 [9] LikharAmruta, D.; Gupta, K. R.; Wadodkar, S. G., International Journal of Pharmacy and

Pharmaceutical Sciences, 2010, 2, 156-161 [10] Suhagia, B. N.; Patel, H. M.; Shah, S. A.; Rathod, I. S.; Marolia, B. P., Indian J. Pharm.

Sci. 2005, 67, 634-637. [11] Hartman, R.; Abrahim, A.; Clausen, A.; Mao, B.; Crocker, L. S.; Ge, Z., J. Liq. Chrom.

Relat. Tech., 2003, 26, 2551-2566. [12] Mandal, U.; Rajan, D. S.; Bose, A.; GowdKa, V.; Ghosh, A.; Pal, T.K., Indian. J. Pharm.

Sci., 2006, 68, 485-489. [13] Rose, M. J.; Agrawal, N.; Woolf, E. J.; Matuszewski, B. K., J. Pharm. Sci., 2002, 91, 405-

416. [14] Matthews,C. Z.; Woolf, E. J.; Lin, L.; Fang, W.; Hsieh, J.; Ha, S.; Simpson, R.;

Matuszewski, B. K., J. Chromatogr. B. Biomed. Sci. Appl., 2001,751, 237-46. [15] Patel, H. M.; Suhagia, B. N.; Shah, S. A.; Rathod, I. S., Ind. J. pharm. sci. 2007, 69, 703-

705 [16] Maheshwari, G.; Subramanian, G. S.; Karthik, A.; Ranjithkumar, A.; Musmade, P.;

Ginjupalli, K.; Udupa, N., JPC – Journal. of Planar. Chromatography. – Modern. TLC., 2007, 20, 335-339.

[17] Brautigam, L.; Nefflen, J. U.; Geisslinger, G., J. Chromatogr. B. Analyt. Technol. Biomed. Life. Sci., 2003, 788. 309-315

[18] Brum, L. Jr.; Fronza, M.; Ceni, D. C.; Barth, T.; Dalmora, S. L., J AOAC. Int., 2006, 89, 1268 -1275.

[19] Ramkrishna, N. V. S.; Vishwottam, K. N.; Wishu, S.; Koteshwara, M., J. Chromatograph. B. 2005, 816, 215-221.

[20] Werner, U.; Werner, D.; Hinz, B.; Lambrecht, C.; Brune, K., Biomed. Chromatogr. 2004, 19, 113-118

[21] Singh, R. M.; Ansari, T. A.; Jamil, S.; Mathur, S. C.; Raj. Shiv.; Singh, G. N., Indian. Drugs., 2005, 42, 56-58.

[22] Carlucci G., Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 2009, 8, 22-37.

[23] Pavan Kumar, V. V.; Vinu, M. C. A.; Ramani, A. V.; Mullangi, R.; Srinivas, N. R., Biomedical Chromatography, 2005, 20, 125-132.

[24] Bhattacharyya, I.; Bhattacharyya, S. P., Asian J. Research. Chem., 2009, 2, 297-303 [25] Liberato, B. J.; Danieli, C. C.; Marcio, F.; Paulo, R. O.; Sérgio, L. D., Journal of Liquid

Chromatography & Related Technologies, 2006, 29, 123-35 [26] Sérgio, L. D.; Liberato, B. J.; Ricardo, M. F.; Paulo, R. O.; Thiago, B.; Maximiliano, S. S.,

Quim. Nova.. 2008, 31, 574-578 [27] Mostafa, G. A. E.; Ghazy, S. E., Annali. di Chimica, 2003, 93, 691-699. [28] Yuan, J.; Yao, S. A., Talanta, 2002, 58, 641-648. [29] Riahi, S.; . Mousavi, M. F.; Bathaie, S. Z.; Shmsipur, M., Anal. Chim. Acat., 2005, 548,

192-198. [30] Shamsipur, M.; Jalali, F.; Ershad, S., J. Pharm. Biomed. Analysis, 2005, 37, 943-947 [31] Craggs, A.; Moody, G. J.; Thomas, J. D. R., J. Chem. Edu., 1974, 51, 541-544. [32] Umezawa, Y.; Hlmann, Ph. B.; Umezawa, K.; Tohda, K.; Amemiya Sh., Pure. Appl.

Chem., 2000, 72, 1851-2082. [33] Umezawa, Y.; Umezawa, K.; Sato, H., Pure. Appl. Chem., 1995, 67, 507-518. [34] Peter, G.; Hayes, J. M.; Hieftje, G. M., Saunders Philadelphia, USA. 1974. [35] Baumann, E., Anal. Chim. Acta., 1968, 42, 127-132. [36] Issa, Y. M.; Hassouna, M. M.; Abdel-Gawad, F. M., Hussien, E. M., J. Pharm. Biomed.

Anal., 2000, 23, 493-502. [37] Stefan, R. I.; Aboul-Enein, H. Y.; Baiulescu, G. E., Pharmazie, 1997, 52, 780-783. [38] Arvand, M.; Vejdani, M.; Moghimi, M., Desalination. 2008, 225 , 176-184.