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Journal of Natural Sciences and Mathematics

Qassim University,Vol. 4, No. 2, PP 135-148 (December 2010/Muharram 1432H.)

135

PVC Membrane Ion-selective Electrode for the Determination of Bamifylline-

HCl in Pure Solution and in Pharmaceutical Preparations

Mahmoud Abou-Dan*, Youssef Ahmed**, and A. Kurdi**Chemistry Department, Faculty of Science, University of Aleppo, SYRIA

**Chemistry Department, Faculty of Science, Cairo University, Giza, EGYPT

E-mail: [email protected]

(Received 12/4/ 2010, Accepted 28/6/ 2010)

Abstract.A new Bamifylline (Bf) ion-selective PVC membrane electrode based on the ion-pair complexof Bamifylline hydrochloride (Bf-HCl) with sodium tetraphenylborate (TPB) was prepared and itsperformance characteristics were studied. The electrode exhibited a linear response with a good Nernstianslope over a relatively wide range of concentrations. The electrode membrane which made of 8.0% (w/w)of ion pair Bf-TPB, 46% (w/w) of tricresyl phosphate (TCP) and 46% (w/w) of poly vinyl chloride (PVC)showed higher characteristics than those obtained with the other ones, namely, slope was 57.82 mV perconcentration decade, at 25C; usable concentration range 1.0010

-5-1.0010

-2M Bamifylline; the limit

detection is 4.5810-6

. response time /10sec. The changes in pH did not affect the electrode performancewithin the range 3.0-/7.5. The standard electrode potentials were determined at different temperatures andused to calculate the isothermal coefficient of the electrode. The electrode showed very good selectivityfor Bf with respect to a large number of inorganic and organic cations. The direct measurement methodwas used to determine Bf in pure solutions and pharmaceutical formulations.

Keywords. Ion-selective electrode, PVC membrane, Bamifylline hydrochloride, sodium tetraphenylborate,Nernst Slope .

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Mahmoud Abou-Dan et al.136

1. Introduction

Bamifylline hydrochloride 7-[2-[Ethyl (2-hydroxyethyl) amino] ethyl] -3,7-dihydro-1,3-dimethyl-8- (phenylmethyl)-1H-purine - 2, 6 - dione; 8 - benzyl - 7 - [2- [ethyl(2- hydroxyethyl) amino]ethyl]theophylline is a stimulant drug of xanthine chemicalclass that is used in the treatment of asthma and reversible airway obstructions.,CAS Registry: [20684-06-4] , Molecular formula C20H27N5O3.HCl , Molecularweight 421.93g/mol , Melting Point: 185-186C, soluble in water, methanol andethanol. The physico-chemical and pharmacokinetic properties of bamifylline differfrom those of theophylline . A pilot trial showed it to produce a significant increasein Forced expiratory volume in 1 s (FEV1) in patients with chronic bronchitis whengiven intravenously, but double-blind studies in a further group of patients showed itto be a inferior to aminophylline and to have more undesirable side effects than thelatter. This drug may cause some side effects (less or more annoying for some

bodies): nausea, vomiting , dizziness stomach , headache and Sleep disturbances.Bamifylline used carefully in cases (Heart diseases, Thyroid gland diseases,Epilepsy, Dangerous liver diseases and Gastric ulcers ), but can not be used in case(Intermittent Porphyria ) [1-5].

Several methods have been reported for the quantitative determination of Bf-HCl. such as HPLC [6-15] , TLC [16] and ISE using phosphomolybdate as reagent[17] . Most of these methods involve several time-consuming manipulation stepsand require sophisticated instruments.

In the present work, plastic membrane-selective electrodes of theconventional type have been constructed. The electrodes are based on incorporationof Bamifylline tetraphenylborate (BfTPB) ion-pair in (PVC) membraneplasticized with dioctylphethalate (DOP) , dibutylphethalate (DBP) or tricresylphosphate (TCP).

Bamifylline Hydrochloride

2. Experimental

2.1. Reagents and materials

All chemicals used were of analytical or pharmaceutical grade. Double-distilled waterwas used for preparing solutions . Sodium tetraphenylborate was Aldrich products .DOP, TCP and DBP were Fluka products, while PVC of relatively high molecular

N

N N

N

O

H3C

O

CH3

N

OH

CH3

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PVC Membrane Ion-selective Electrode 137

weight, and tetrahydrofuran (THF) were Merk products. Theophylline and Caffeine wasobtained from (SHIFA Pharmaceutical Industries-Syria). Bamifylline hydrochloride wasobtained as gift from manufacturer accompanied with its certificate of analysis and wasused as working standard without further treatment .

A stock solution of 0.01M Bf-HCl was prepared daily by dissolving theappropriate amount of the drug in double-distilled water and stored in dark bottles.More dilute solutions were prepared by appropriate dilution. Sodium hydroxide andhydrochloric acid solutions of concentrations within the range 0.11.0M were usedfor adjusting the pH of the medium, while 0.1M NaCl solution was used foradjusting the ionic strength.

Bamifyllin-HCl 750, 250mg as Suppository were purchased from Eblapharmaceutical industry under trade name Bamifyllin750 , Bamifyllin250 ,respectively .

2.2. Preparation of the ion-pairBf-TPB was prepared by mixing equal volumes of equimolar solutions ofBamifylline hydrochloride (Bf-HCl) and sodium tetraphenylborate (TPB) and keptfor 12 h in dark place for complete precipitation. The white precipitate was filtered,washed with water and kept at room temperature for 24 h to obtain the electroactiveion-pair.2.3. Preparation of electrodes

The membrane components (850 mg) were dissolved in THF (10 ml) andpoured into a 7.5 cm petridish. Overnight evaporation of the solvent yielded amembrane of 0.1mm thickness, and visually determined by an optical microscope.For each electrode, a disk of the membrane with a 14mm diameter was punchedfrom the large membrane and glued to the polished end of a 2 cm long PVC tube,which attached to one end of a 15 cm glass tube.

The electrodes were then filled with 0.1M KCl and 102M Bf-HCl (1 : 1)

solution and the Ag/AgCl wire was immersed in this solution. The resultantelectrodes were preconditioned by soaking them for 50min in 102M Bf-HClsolution. The electrochemical system is composed as follows:

Ag/AgCl/inner solution/membrane/test solution//3M KCl salt bridge//Hg/Hg2Cl22.4. Construction of the calibration graphs

Suitable increments of standard solution of (Bf-HCl) were added to 50 mldouble-distilled water to cover the concentration range 1.20106 to 8.00102M. Thesensor and the reference electrodes were immersed in the solution and after each additionthe potential value was recorded at 25C. The cell potentials, Ecell, were recorded andplotted versus -logBf-HCl [18].2.5. Selectivity of the electrodes

The selectivity coefficients were determined by the separate solution method(SSM) [19], where the following equation was applied:

1/ZZABpotAB ]log[B-log[A]

S

)E(ElogK ++

=

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where EAis the electrode potential in 102M Bf-HCl solution, EBthe potential of the

electrode in 102M interferent solutionBand S the slope of the calibration graphs.In addition to the SSM, the selectivity of the investigated electrodes weredetermined by the matched potential method (MPM) [20-21]. In this method, thepotentiometric selectivity coefficient is defined as the activity ratio of primary andinterfering ions that give the same potential change under identical conditions. At

first, a known concentration 'aA of the primary ion solution is added into a

reference solution that contains a fixed concentration Aa of primary ions, and thecorresponding potential E is recorded. Next, solution of an interfering ion is addedto the reference solution until the same potential change E is recorded. The changein potential at the constant background of the primary ion must be the same in both .

BAA

pot

AB

a)a'(aK =where aBis the concentration of the interfering ion.

3. Results and discussion

3.1. Characterization and optimization of the electrodes

It is well known that the sensitivity and selectivity of the ion-selective electrodes notonly depend on the nature of ion-exchanger used [22], but also significantly on themembrane composition [23-24], the nature of plasticizers [25] .

The influence of the plasticizer type and its amount on the characteristics ofthe Bf-TPB electrode was investigated by using three plasticizers with differentpolarities including DBP, DOP and TCP. Different plasticizer/PVC (w/w) ratioswere studied. As seen in (table 1), TCP was found to be the most effectiveplasticizers in preparing Bf-TPB electrode (i.e. Membranes No. 21, 22 and 23). It isnoteworthy that, the nature of the plasticizer influences the mobility of ions and

provides the appropriate conditions for incorporation of Bf-HCl ion into themembrane prior to its exchange with the soft ion-exchanger. The electrodescontaining DBP (Membranes No. 11-19) exhibited lower slopes and responseranges.

Besides the critical role of the nature and the amount of plasticizer inpreparing Bf-TPB electrode, the influence of the amount of Bf-TPB on the potentialresponse of the Bf-TPB electrode was investigated. As shown in (table 1), theamount of Bf-TPB strongly affects the sensitivity of the electrodes (i.e. MembranesNo. 1-4). The response of the electrode increases with increasing the ion-exchangercontent. The use of more than 6% ion-exchanger resulted in improved responsecharacteristics and selectivity of the Bf-TPB electrode (i.e. Membrane No. 1-10).

Among the different compositions studied, the membrane incorporating 8%Bf-TPB, 46% TCP and 46% PVC (Membranes No.22 exhibits the best responsecharacteristics in solutions containing Bf. Therefore, this composition was used tostudy various operation parameters of the electrodes.

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Table (1) . Effect of the membrane composition on the characteristics of the proposed Bf-selective

electrodecomposition

*Pl.Linear range

M

**D.L.

M

slop

mV/decadePVC

%(w/w)

Ion Pair

%(w/w)%(w/w)Type

No.

2.0010-5

-8.0010-3

1.2910-553.320.27a476471

2.0010-5

-8.0010-3

9.5510-655.220.19a46.5746.52

1.4010-5

-1.0010-2

7.9110-657.110.15a468463

1.4010-5

-1.0010-2

5.9110-658.370.11a45.5945.54

1.4010-5

-1.0010-2

7.9410-656.270.15a4510455

2.0010-5

-8.0010-3

1.0310-555.140.21a409516

2.0010-5

-8.0010-3

1.2010-552.150.32a369557

3.7910-5-6.0010-32.0710-548.840.43a519408

2.0010-5

-6.0010-3

1.0410-554.180.22a428509

2.7910-5

-6.0010-3

1.3510-550.390.37a37855

DOP

10

3.5910-5

-2.4910-3

1.9010-553.220.28a4764711

2.5910-5

-6.0010-3

1.0410-556.340.19a46.5746.512

2.5910-5

-6.0010-3

1.2110-554.480.25a4684613

3.5910-5

-4.0010-3

1.8510-551.710.40a45.5945.514

5.1710-5

-4.0010-3

2.6210-548.510.46a45104515

3.5910-5

-6.0010-3

1.7610-554.910.23a4275116

3.5910-5

-4.0010-3

2.3910-552.100.31a3875517

5.1710-5

-4.0010-3

2.6810-549.200.39a5374018

3.5910-5-4.0010-32.1310-551.830.37a42850

DBP

19

1.2010-5

-8.0010-3

1.1910-553.440.22a4764720

1.4010-5

-8.0010-3

8.0910-656.420.13a46.5746.521

1.0010-5

-1.0010-2

4.5810-657.820.11a4684622

1.0010-5

-1.0010-2

6.3310-656.980.14a45.5945.523

1.4010-5

-1.0010-3

7.8910-654.650.20a45104524

2.0010-5

-8.0010-3

9.3110-653.700.26a4095125

2.0010-5

-8.0010-3

9.7010-651.640.36a3695526

3.7910-5

-4.0010-3

1.5910-545.920.51a5194027

1.4010-5

-6.0010-3

8.3610-655.180.19a4285028

2.0010-5

-6.0010-3

1.2310-551.160.33a37855

TCP

29

(* Pls.: Plasticizer , ** D.L.: detection limits)aStatistical deviation (four preparations).

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Fig. (1) . Calibration graphs for the best membranes using different plasticizer A(DOP), B(DBP),

C(TCP) & 1-3(I.P.7%), 4-6(I.P.8%), 7-9(I.P.9%)

3.2. Effect of soaking

Calibration plots (pBf vs. E, mV) were obtained after the electrode wassoaked continuously in 102 M Bf-HCl for different times (fig.2). The resultsshowed that the best soaking solution with stable value was 102M Bf-HCl for 50min.

0246

A1pC

mV,E

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

0246

A4

A7

B2

B5

B8

C3

C6

C9

A1 A4 A7

B2

B5 B8

C3

C6 C9

0246

0246

0246

0246

0246

0246

0246

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Fig. (2) : Effect of soaking

3.3. Response time and Lifetime of electrode

The response time of an ion-selective electrode is an important factor inanalytical applications, and depends slightly on the concentration change, which was

determined according to the IUPAC recommendations [26]. Therefore, it was

determined by recording the time elapsed to reach a stable potential value after the

electrode and the reference electrode were immersed in calibration solutions from

low to high Bf ion concentrations. If the concentration of Bf was changed from

4.0105to 4.0104M, the response time was 10 sec, but for concentrations higher

than 4.0104M, the response time decreased was less than 10sec .

The proposed electrode can be used at least for 33 day without any

considerable change in potential response.

3.4. Effect of pH

The effect of pH of the test solution ( 4.0010-5

M, 4.0010-4

M and 4.0010-

3M Bf-HCl) on the electrode potential was investigated by following the variation ofpotential with change in pH by the addition of very small volumes of HCl or NaOH

mV,E

-50

-40

-30

-20

-10

0

10

20

30

40

50

60

70

0 60 120 180 240

min,t

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(0.1-1.0 M of each )[27]. From the obtained graph it is clear that the working pH of

the electrode is from 3.0 up to 7.5(fig. 3). The observed potential drift at higher pH

values could be attributed to the formation of the drug base of Bf-HCl in the

solution. At lower pH value, less than 3, the potentials increased indicating that the

electrode responds to both of the Bf-HCl and the hydrogen protons.

Fig. (3). Effect of pH of the test solution on the electrode potential reading (a) 4.0010-5

, (b)

4.0010-4

and (c) 4.0010-3

M Bf-HCl solutions

3.5. Effect of temperature

The effect of temperature on the response of the membrane electrodes wereillustrated in the calibration graphs (fig.4) which constructed at test solutiontemperature 20, 25, 30, 35, 40, 45, 50 , 55 and 60C. The electrodes gave goodNernstian response against the studied temperatures. The standard electrodepotentials, E,were determined at different temperatures and used for calculation ofthe thermal coefficients of the electrodes [28-29] which were found amounting to0.018mV/C for BfTPB membrane electrode, revealing a fairly good thermalstability of the electrode.

-120

-100

-80

-60

-40

-20

0

20

40

60

80

0 2 4 6 8 10 12 14

a

b

c

mV,E

pH

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Fig. (4). Effect of temperature on slope.

3.6. Selectivity

The influence of some inorganic cations, excipients, and some large organiccompounds similar infrastructure to Bamifylline on the Bf electrode was investigated,the selectivity coefficients determined by the separate solution method (SSM) andmatched potential method (MPM) (table 2). None of the investigated species were found

to interfere as shown by the very small values of potABK . This reflects a very highselectivity of the investigated electrode toward the Bamifylline cation.

Table (2) . Selectivity coefficients, for Bamifylline -responsive electrode using SSM and MPM

potABK potABKInterferent

SSM MPM

Interferent

SSM MPM

Ba2+ 8.35 10-5 4.18 10-5 Na+ 7.15 10-4 2.42 10-4

Mn2+ 5.94 10-4 6.58 10-4 K+ 7.66 10-4 1.83 10-4

Ni2+ 5.43 10-5 7.34 10-4 +4NH 8.43 10

-4 4.11 10-4

Cu2+ 2.17 10-4 7.16 10-4 Li+ 5.14 10-4 2.82 10-4

Zn2+ 5.89 10-5 2.88 10-4 Caffeine 4.61 10-4 6.73 10-3

57.0

57.1

57.2

57.3

57.4

57.5

57.6

57.7

57.8

57.9

58.0

15 25 35 45 55 65

slope

C,T o

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Continue table (2)

potABK potABKInterferent

SSM MPM

Interferent

SSM MPM

Pb2+ 1.52 10-5 3.47 10-4 Theophylline 5.43 10-4 4.19 10-3

Cd2+ 7.31 10-5 6.81 10-4 Witepsol H 15 - 7.58 10-5

Cr3+ 5.16 10-4 1.55 10-4 Witepsol H 35 - 6.32 10-5

Fe3+ 7.22 10-4 6.86 10-3 PEG4000 - 2.83 10-5

Mg2+ 6.74 10-5 6.44 10-5 PEG1000 - 1.35 10-5

Ca2+ 2.81 10-3 7.62 10-4 Erozil - 4.69 10-5

3.7.Analytical applications

-Determination of Bf-HCl in pure solutionsThe electrode (No.22) was successfully applied to the determination of

Bamifylline hydrochloride pure solutions, (at constant temperature of 25C.Different standard concentrations of Bf-HCl were used in the determination. Resultsshowed that the electrode had good recovery values which ranged from 100.98 to102.80%, while relative standard deviation (RSD) values ranged from 0.55 to 2.10%(table 3).These results indicated that the used method represent high accuracy.-Determination of Bf-HCl in pharmaceutical preparations

Bamifylline hydrochloride was determined in pharmaceutical preparationspotentiometrically using the electrode (No.22) .

The contents of 10 suppositories of Bamifyllin750 (750mg/Supp) were mixed

and melted. An accurate weight of the melted suppositories equivalent to 750 mg ofBf-HCl were taken . This weight was dissolved in 200 ml distilled water for 1h at50C with continuous stirring, then the solution cooled and filtrated, and thisprocess repeated twice with 100ml distilled water, and the total volume diluted to500ml . Then 10ml of the last solution were diluted to 50ml with the same solventand subjected to the potentiometric determination using the proposed electrode.

The values of RSD and recovery given in (table 4) proved that the electrode wassuccessful for the determination of Bf-HCl in the pharmaceutical preparations. Theseresults were compared with those obtained from the reference method based onspectrophotometry [30].

The calculated values of RSD, R obtained from the determination of Bf-HCl inthe pharmaceutical preparations (Bf250 and Bf750) were closed to reference methodvalues; that RSD and R values in Bf250 were 1.45 and 103.20 %, while in the reference

method were 2.09 and 102.32, respectively, whereas in Bf750 were 1.02 and 102.24%

and in the reference method were 1.48 and 101.52, respectively.

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Table (3) . Determination of Bf-HCl in pure solutions

[Bf-HCl], mMASE, mMR%RSD%SD

CfoundCtaken

0.00048102.082.100.00110.05100.050

0.00065101.741.420.00140.10170.100

0.00151101.780.830.00340.40710.400

0.00262100.980.730.00590.80790.800

0.00372101.550.550.00831.52321.500

101.940.940.01922.03882.000

Table (4 ). Determination of Bf-HCl in pharmaceutical preparations

ASER%RSD%SDiC

Method

1.67103.201.453.74258mg/SuppISE

2.39102.322.095.36255mg/Supp

Bf250mg

UV

3.48102.241.027.79766mg/SuppISE

5.05101.521.4811.28761mg/Supp

Bf750mg

UV

4. Conclusions

The proposed method has an excellent reproducibility, wide linear range, low

detection limit, high sensitivity, good selectivity, and good Nernstian slope which

are an important feature of the system. Most of the response characteristics of theproposed electrode were found to be superior to the previously another electrode

(table 5). The electrode can be used successfully for the determination Bf-HCl in

pure solutions and pharmaceutical preparations. The proposed method can be used

for the routine determination of Bf-HCl in real samples.

Table (5). Comparison of the proposed Bf-HCl-selective electrode with (Ref.17)

This work Ref.17

Slope 57.82 mV/decade 59.38 mV/decade

Detection limit 4.5810-6M 4.1010-4M

Linear range 1.0010-5-1.0010-2M 1.8210-3-6.6710-3M

response time 10sec 20sec

pH range 3.0-7.5 2.0-7.0

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5. References

[1]. VIDAL, Vidal Le Dictionnaire. 80thed., France(2004)1977-1978.

[2]. BUDAVARI S. (Ed.), The Merck index. 14thed., on CD-ROM, Ver. 12:3, 3rd

edn., Chapman Hall/CRCNetBASE(2008).

[3]. CHRISTIAENS Co., Belg. pat. 602,888 (to Christiaens), C.A. 56, 5981c (1962).

[4]. WEINBERGER M, HENDELES M., Vol. 1, 5th edn. Mosby-Year Book Inc., St

Louis, (1998) 589611.

[5]. TURNER P, CATTRELL WR, PATTERSON DS., Journal of New Drugs,

5(1965)333-336.

[6]. FOURTILLAN J. B., BRISSON A. M., LEFEBVRE M. A., Journal of Annales

Pharmaceutiques Francaises (Paris), 41(1),(1983) 37-43.

[7]. NICOT G., LACHATRE G., GONNET C. , ROCCA J. L., VALETTE J. P.,MERLE L., NOUAILLE Y., Journal of Chromatography B: Biomedical Sciences

and Applications, 277(1983) 239-249.

[8]. GERLO E., MAES V., Journal of Clinical Chemistry, 34(8),( 1988) 1657.

[9]. BELLIARDO F., LUCARELLI C., Journal of Chromatography A, 535(1-2),

(1990)305-309.

[10]. CARLUCCI G., COLANZI A., MAZZEO P., Journal of Pharmaceutical and

Biomedical Analysis, 8(8-12), (1990)1067-1069.

[11]. TURCANT A., PERMEL-CABIC A., CAILLEUX A., ALLAIN P., Journal of

Clinical Chemistry, 37(7),( 1991) 1210-1215.

[12]. PAPADOYANNIS I.,SAMANIDOU V.,PANOPOULOU G. D.,Journal of Liquid

Chromatography, 15(17),( 1992) 3065-3085.

[13]. PAPADOYANNIS I., SAMANIDOU V., ZOTOU A., Journal of LiquidChromatography, 16(17), (1993)3847-3861.

[14]. PAPADOYANNIS I., SAMANIDOU V., ZOTOU A., TSIONI G., Journal of

Liquid Chromatography, 16(17), (1993)3827-3845.

[15]. THEODORIDIS G., PAPADOYANNIS I., VASILIKIOTIS G., H. TSOUKALI-

PAPADOPOULOU H., Journal of Chromatography. B: Biomed. Sc. Appl.,

668(2),(1995) 253-263 .

[16]. ROMANO G., CARUSO G., MUSUMARRA G., PAVONE D., CRUCIANI

G., Journal of Planar Chromatogr-Mod. TLC, 7(3),(1994) 233-241.

[17]. ABOU-DAN M., MA'AROOF M., NAJJARI S., Journal of Tishreen

Univ.,(2007) 116-131

[18]. BADAWY S.S., AHMED F. Y., ALI A. MUTAIR., Journal of Anal. Chim. Acta,

511 (2004) 207214.

[19]. BUCK R.P., LINDNER E., Journal of Pure Appl. Chem., 66 (1994) 227.

8/10/2019 238-444-1-SM

13/14


[20]. UMEZAWA Y., BHLMANN P., UMEZAWA K., TOHDA K., AMEMIYA

S., Journal of Pure and Applied Chemistry, 72(10),(2000) 1851-2082.

[21]. V. K. GUPTA, M. Al HAYAT, A. K. SINGH, M. K. PAL, Journal of Anal.

Chim. Acta, 634 (2009) 36.

[22]. S. KAMATA, A. BALIALE, Y. FUKONAGA, A. MURATA, Journal of Anal.

Chem., 60 (1988) 2464.

[23]. N.A. El-RAGHEH, A.M. KOSASY, S.S. ABBAS, S.Z. EL-KHATEEB,

Journal of Anal. Chim. Acta, 418 (2000) 93.

[24]. KHALIL , M.A. EL-RIES, Journal of Talanta, 59 (2003)1260.

[25]. M. SHAMSIPUR, M. YOUSEFI, M.R. GANJALI, Journal of Anal. Chem., 72

(2000) 2391.

[26]. CARLO M. , Journal of Analytica Chimica Acta, 512 (2004) 183-190[27]. RAUL A. SANCHEZ-MORENO, Analytica Chimica Acta, 634 (2009) 6874.

[28]. ANTROPOV L.I., Theoretical Electrochemistry, Mir, Moscow,(1972)267-271.

[29]. NALWA H.S. , LIN Y. (Ed) Handbook of electrochemical nanotechnology,

Vol. 1-2 , American Scientific, Stevenson Ranch, CA 2009.

[30]. RAFEL T. G., MARQUES L. A.,. Therapie, 23,(1981) 457-468.

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* ***

*J

**J

F LL J LL E

.

Bf-HCl TPBK

PVC F DOP

DBP TCPE 8%(w/w)

Bf-TPB46%(w/w) TCP46%(w/w)PVC

1.0010-5

-1.0010

-2

M 4.5810-6

57.82 mV/decade 25CK pH

5.70.3pH =

K

10secK

MPM SSM

K

K

238-444-1-sm

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