Comunicacion oral eseac_2010 [modo de compatibilidad]

DIFFERENTIAL POTENTIOMETRY AND DIFFERENTIAL POTENTIOMETRY AND

DIFFERENTIAL DYNAMIC RESPONSE WITH IONDIFFERENTIAL DYNAMIC RESPONSE WITH ION

SELECTIVE ELECTRODES: APPLICATION TO SELECTIVE ELECTRODES: APPLICATION TO

CYCLODEXTRINECYCLODEXTRINE--BASED DRUG SELECTIVEBASED DRUG SELECTIVE

ELECTRODESELECTRODESELECTRODESELECTRODES

María CuarteroMaría Cuartero , Joaquín A. Ortuño and MªSoledad García

MÉTODOS AUTOMÁTICOS DE ANÁLISIS. SENSORES QUÍMICOS

“AUTOMATIC METHODS OF ANALYSIS. CHEMICAL SENSORS”

Department of Analytical Chemistry. Faculty of Chemistry

University of Murcia. Murcia. Spain

IONION--SELECTIVE ELECTRODESSELECTIVE ELECTRODES

ISEsISEsSelectivity

Sensitivity

Simplicity Rapid response

Longterm

Wide linear range

Low cost

Applications

PLASTICIZED POLYMERIC MEMBRANES

Longterm stability

Low cost

PVCPlasticizer

Ionic additiveIonophore

The appropriate selection of the components enables the selectivity of the ISE to be controlled.

Dynamic response Dynamic response studiesstudies

Response time of the sensor

Working mechanism

Practical applications

important

(E vs t)

Interfering ions

Data matrix (E and t)

Qualitative and quantitative purposes

particulary relevant

exploited

SOFTWARETWO-ELECTRODE POTENTIOMETRY

electrode 1

reference electrode

electrode 2

ELECTRODE 1

ELECTRODE 2

REFERENCE ELECTRODE

High impedance buffers

Analogmultiplexer

A/D converter16 bits+

-

Reference voltage2.5 V

Digital control

Controller

USB interface

PC

ELECTRODE 1

ELECTRODE 2

REFERENCE ELECTRODE

High impedance buffers

Analogmultiplexer

A/D converter16 bits+

-

Reference voltage2.5 V

Digital control

Controller

USB interface

PC

The potential difference between twoISEs are alternatively measured bymeans of two analog circuits, a fastmultiplexer and an analog-to digitalconverter. The potential differencebetween both ISEs is obtained bydigital substraction of the previousrecording.

This procedure has the advantage thatnot only is the potential differencebetween two ISEs monitored but alsothe potential of each electode.

TwoTwo--electrode potentiometryelectrode potentiometry


Electrode 1

Electrode 2


Electrode 1

Electrode 2

DIFFERENTIAL DYNAMIC RESPONSE (DDR)DIFFERENTIAL DYNAMIC RESPONSE (DDR)

TwoTwo--electrodes potentiometryelectrodes potentiometry

Electrode 1

Electrode 2

DIFFERENTIAL DYNAMIC RESPONSE (DDR)DIFFERENTIAL DYNAMIC RESPONSE (DDR)

DIFFERENTIAL DIFFERENTIAL POTENTIOMETRY (DP)POTENTIOMETRY (DP)

The potential difference between both electrodes once that the steady-state value has

been attained

Overall potential response

E (∆Go, βCD-drug , …)

The direct transfer of the ionic drug from water to

the plasticizer is favourable.

Formation constant of complexes between CD and drug are not very

high.

OR''

O

H

ORH

O

n

R'O

n=6 � α-CD

n=7 � β-CD

n=8 � γ-CD

alkylated cyclodextrin-based drug selective electrodes



The direct transfer of the ionic drug from water to

the plasticizer is favourable.

Formation constant of complexes between CD and drug are not very

high.

benzoyl beta-cyclodextrin derivative



The direct transfer water-plasticizer is very favourable

Not very high


AntiarrhytmicAntiarrhytmic

N

N

O

HO

H

H

H2N

O

N

Procainamide

Quinidine

AntimalarialAntimalarial

N

N

HO

O

H

H

Quinine

AntidepressantAntidepressant

N

N

Clomipramine

AnesthesicsAnesthesics




Not very high



HN

N

O

BupivacaineHN N

O

Lidocaine

H2N

O

N

O

Procaine

NH

O

N

O

TetracaineN

O

O

O

O

Papaverine

AntispasmodicAntispasmodic


Lidocaine





Not very high

HN

N

O

BupivacaineHN N

O

Lidocaine

H2N

O

N

O

Procaine

NH

O

N

O

TetracaineN

O

O

O

O

Papaverine


lipophilic aromatic ring system and a nitrogen that can be protonated to provide

a cationic drug


E (∆Go, βCD-drug , βCD-plasticizer …)


Not very high

Neutral, lipophilic CDs manifest recognition by three types of interactions:

� conventional hydrophobic bonding

� -N-H…O and N-C-H…O hydrogen bonding

� van der Waals’ forces.


Lidocaine


HN

N

O

BupivacaineHN N

O

Lidocaine

H2N

O

N

O

Procaine

NH

O

N

O

TetracaineN

O

O

O

O

Papaverine


lipophilic aromatic ring system and a nitrogen that can be protonated to provide

a cationic drug


E (∆Go, βCD-drug , βCD-plasticizer …)


Not very high

Neutral, lipophilic CDs manifest recognition by three types of interactions:

� conventional hydrophobic bonding

� -N-H…O and N-C-H…O hydrogen bonding

� van der Waals’ forces.


ELECTRODE 1ELECTRODE 1

MembraneMembrane:

100 mg Polyvinyl chloride (PVCPVC) 30%30%

200 mg PlasticizerPlasticizer 60%60%

30 mg Heptakis(2,3,5-tri-O-benzoyl)-β-cyclodextrin (ββ--CDCD) 9%9%

3 mg tetrakis[3,5-bis-(trifluoromethyl)phenyl]borate (TFMPBTFMPB) 1%1%

ELECTRODE 2ELECTRODE 2

Blank Membrane:Blank Membrane:

100 mg PVCPVC 33%33%

200 mg PlasticizerPlasticizer 66%66%

3 mg TFMPBTFMPB 1%1%

MEMBRANES ASSAYEDMembranes DOS NPOE TCP FNDPE PVC TFMB Β-CD

A - - - 66 33 1 -

B - - - 60 30 1 9

C - - 66 - 33 1 -

D - - 60 - 30 1 9

E - 66 - - 33 1 -

F - 60 - - 30 1 9

G 66 - - - 33 1 -

H 60 - - - 30 1 9

dioctyl sebacate (DOS), 2-nitrophenyl octyl ether (NPOE), tricresyl phosphate (TCP), 2-fluoro-2’-nitrodiphenyl ether (FNDPE), polyvinyl chloride (PVC) , potassium tetrakis[3,5-bis-(trifluoromethyl)phenyl]borate (TFMB) and

Heptakis(2,3,5-tri-O-benzoyl)-β-cyclodextrin (β-CD)


A - - - 66 33 1 -

B - - - 60 30 1 9

C - - 66 - 33 1 -

D - - 60 - 30 1 9

E - 66 - - 33 1 -

F - 60 - - 30 1 9

G 66 - - - 33 1 -

H 60 - - - 30 1 9



H2O

Ag-AgCl │KCl (1x10 -4 M)│internal solution, 1x10 -4 M KCl│PVC membrane │sample solution

Reproducible initial stage The electrodes were conditioned in deionized

water until they reached a constant potential


A - - - 66 33 1 -

B - - - 60 30 1 9

C - - 66 - 33 1 -

D - - 60 - 30 1 9

E - 66 - - 33 1 -

F - 60 - - 30 1 9

G 66 - - - 33 1 -

H 60 - - - 30 1 9



Ag-AgCl │KCl (1x10 -4 M)│internal solution, 1x10 -4 M KCl│PVC membrane │sample solution

Reproducible initial stageA flux of potassium ions from the inner solution

to the sample solution is established until a steady-state concentration profile inside the

membrane is reached, which is manifested as a CONSTANT ELECTRODE POTENTIALCONSTANT ELECTRODE POTENTIAL

Concentration perturbation (Input)Concentration perturbation (Input)

Standard addition methodStandard addition method

Adding consecutive volumes of concentrated solution of the

different drugs


log C

time


log C

time

The duration of each step depended on the electrode response observed and, in general, decreased as the

concentration was increased.

SAMPLE SOLUTION

ION-SELECTIVE MEBRANE INTERNAL SOLUTION

δaq δm

[CD-K]

aJ(bulk)

CONCENTRATION PROFILESCONCENTRATION PROFILES

aK

[CD-J]

aDaK(bulk)

K= potassium

J= ionic drug

CD= cyclodextrin

δ= diffusion layer

during exposure to the corresponding ionic drug, a flux towards the filling solution is established, couple d to a

flux of potassium in the opposite direction

MEMBRANEMEMBRANE INTERNAL SOLUTION INTERNAL SOLUTION SAMPLE SOLUTIONSAMPLE SOLUTION

K+

K+

K+

K+

J+

J+

J+

J+ J+ J+

CD

K

K+

K+

KCl 10KCl 10 --44 MM

K+

K+

J+

J+

J+

J+

K+K+

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

DOS TCP

1

2

3

4

56

7 8

1

2

3

45 6 87

DDR of lidocaine (different plasticizers)DDR of lidocaine (different plasticizers)

t / s0 500 1000 1500 2000

E1-

E2

/ mV

-50

0

50

100

150

200

250

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-

E2

/ mV

-50

0

50

100

150

200

250

NPOE FNDPE

12

3

4

5

68

1 2

3

4

56

87

7

(1) 0 M, (2) 1x10-6 M, (3) 5x10-6 M, (4) 1x10-5 M, (5) 5x10-5 M, (6) 1x10-4 M, (7) 5x10-4 M, (8) 1x10-3 M

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

200

250

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

4

1

2

3

45 6 8

4

7

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

200

250

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

4

1

2

3

45 6 8

4

7


The lidocaine concentration at which this inversion occured

depend on the plasticizer used. For

DOS, NPOE and FNDPE increased with the dielectric constant

(ε=4, 24 and 50 respectively).

t / s0 500 1000 1500 2000

E1-E

2 / m

V

-50

0

50

100

150

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

12

3

5

68

1 2

3

56

87

7


t / s0 500 1000 1500 2000

E1-E

2 / m

V

-50

0

50

100

150

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

12

3

5

68

1 2

3

56

87

7


respectively).

The potential corresponding to the

inversion was roughly the same for these three plasticizers.

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

200

250

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

4

1

2

3

45 6 8

4

7

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

200

250

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

4

1

2

3

45 6 8

4

7


One drawback of the membranes

constructed with DOS, NPOE and FNDPE, is that the response is

not reproducible because the membrane can not be regenerated after a concentration

perturbation.

t / s0 500 1000 1500 2000

E1-E

2 / m

V

-50

0

50

100

150

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

12

3

5

68

1 2

3

56

87

7


t / s0 500 1000 1500 2000

E1-E

2 / m

V

-50

0

50

100

150

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

12

3

5

68

1 2

3

56

87

7


perturbation.

DOS, NPOE and FNDPE �� none reproducible

TCP �� reproducible

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

200

250

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

4

1

2

3

45 6 8

4

7

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

200

250

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

4

1

2

3

45 6 8

4

7


In contrast, the membrane constructed with TCP displayed a much lower potential

respose but its response was reproducible.

The different behaviour displayed by TCP can

t / s0 500 1000 1500 2000

E1-E

2 / m

V

-50

0

50

100

150

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

12

3

5

68

1 2

3

56

87

7


t / s0 500 1000 1500 2000

E1-E

2 / m

V

-50

0

50

100

150

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

12

3

5

68

1 2

3

56

87

7


displayed by TCP can be explained from

some results reported in the literature that

point to an interaction between TCP and

protonated amines.

DOS, NPOE and FNDPE �� none reproducible

TCP �� reproducible

DP of lidocaine (different plasticizers)DP of lidocaine (different plasticizers)

150

200

250

Plots of DP versus logarithmic concentration of lidocaine

The response of the electrode containing CD is higher than the response

log [L] / M

-6 -5 -4 -3

mV

-50

0

50

100

150DOS TCP NPOE FNDPE

higher than the response of the electrode without CD at low concentration,

while the response is more similar at higher

concentrations.

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

DDR of different ionic drugs (membranes with TCP)DDR of different ionic drugs (membranes with TCP)

LIDOCAINEPROCAINE

81

2

3

4

576

1

2

3

46 85 7

t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

t / s


CLORMIPRAMINEPAPAVERINE

81

2

34

5 6 78

1

2

34

657

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

80

100

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

LIDOCAINE


PROCAINE

2

81

2

3

4

576

1

2

3

46 85 7

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

80

100

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

80

100

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

LIDOCAINE


PROCAINE

2

81

2

3

4

576

1

2

3

46 85 7


t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40


CLORMIPRAMINE

81

34

5 6 78

1

2

34

657

t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40

t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40


CLORMIPRAMINE

81

34

5 6 78

1

2

34

657

The more lipophilic the ionic drug (clomipramine>papaverine>lidocaine>procaine), the l ower the inversion

concentration and the higher the inversion potentia l

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

80

100

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

LIDOCAINE


PROCAINE

2

81

2

3

4

576

1

2

3

46 85 7

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

80

100

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

t / s0 1000 2000 3000

E1-

E2

/ mV

0

10

20

30

40

50

60

80

100

50

60

t / s

0 1000 2000 3000 4000

E1-

E2

/ mV

-20

-10

0

10

20

30

40

LIDOCAINE


PROCAINE

2

81

2

3

4

576

1

2

3

46 85 7


t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40


CLORMIPRAMINE

81

34

5 6 78

1

2

34

657

t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40

t / s

0 1000 2000 3000

E1-

E2

/ mV

0

20

40

60

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2

/ mV

0

10

20

30

40


CLORMIPRAMINE

81

34

5 6 78

1

2

34

657

The different DDR obtained for all the drugs assaye d could well be used for qualitative purposes

DP (membranes with TCP)DP (membranes with TCP)

60

80Na+ K+

Mg2+ Ca2+ NH

4+

TEA

Plots of DP versus logarithmic concentration of the different compounds assayed

log [C] / M

-10 -8 -6 -4 -2

mV

0

20

40

TEA ProcainamideProcaineLidocaineTetracaineBupivacaineQuinidinaQuininaPapaverineClormipramine

Perturbation of concentrationPerturbation of concentrationConcentration perturbation (Input)Concentration perturbation (Input)

log C

The electrode is re-conditioned in deionised

water after each concentration perturbation

time


log C

The electrode is re-conditioned in deionised

water after each concentration perturbation

time

E1-

E2

/ mV

(1d

iv=5

mV

)

DDR of lidocaine (membranes with TCP)DDR of lidocaine (membranes with TCP)

1x10-6 M 5x10-6 M 1x10-5 M

t / s (1div=50 s)

E1-

E2

/ mV

(1d

iv=2

0mV

)

t / s (1div=20 s)

E1-

E2

/ mV

(1d

iv=2

0mV

)

5x10-5 M 1x10-4 M 5x10-4 M

log C mV


time time

CONCENTRATION PERTURBATION

(INPUT=MONOTONIC)DDR

(OUTPUT=NON-MONOTONIC)

This type of signals has been reported for the dyna mic response of several types of ISEs in the presence of interfiring ions.

mV 150

200

250

300

5x10-4 M

1x10-4 M

5x10-5 M

electrode 1

electrode 2 (Blank membrane)m

V 150

200

250

300

5x10-4 M

1x10-4 M

5x10-5 M

electrode 1

electrode 2 (Blank membrane)

electrode 1

electrode 2 (Blank membrane)


t / s (1div=50 s)

E1-

E2

/ mV

(1d

iv=5

mV

) 1x10-6 M 5x10-6 M 1x10-5 M

t / s (1div=50 s)

E1-

E2

/ mV

(1d

iv=5

mV

) 1x10-6 M 5x10-6 M 1x10-5 M

t / s

0 200 400 600 800 1000 1200 1400 1600

mV

0

50

100

1x10-5 M

5x10-6 M

1x10-6 M

t / s

0 200 400 600 800 1000 1200 1400 1600

mV

0

50

100

1x10-5 M

5x10-6 M

1x10-6 M

E1-

E2

/ mV

(1d

iv=2

0mV

)

t / s (1div=20 s)

E1-

E2

/ mV

(1d

iv=2

0mV

)

5x10-5 M 1x10-4 M 5x10-4 M

E1-

E2

/ mV

(1d

iv=2

0mV

)

t / s (1div=20 s)

E1-

E2

/ mV

(1d

iv=2

0mV

)

5x10-5 M 1x10-4 M 5x10-4 M

DDR(NON-MONOTONIC)

DR(MONOTONIC)

150

200

250

Calibration graphs for DP and DDR of lidocaine (mem branes Calibration graphs for DP and DDR of lidocaine (mem branes with TCP)with TCP)

A

BDDR

log [L] / M

-6 -5 -4 -3

mV

-50

0

50

100

E(mV)=724.84+151.44log[L(M)+1.06x10-5]

A

│A│-│B│

CONVENTIONAL DP

rather odd signals

two ionic drug trasport inside the membrane

free ionic drug complexed ionic drug

the difussion of CD to the sample interface is insufficient to complex all the ionic drug arising from the

sample solution

lower concentrations higher concentrations

CONCLUSIONSCONCLUSIONS

I. The new differential dynamic response technique,applied to ion-selective electrodes, and exploited herefor the first time, is a source of signals not usuallyseen that can be useful for quantitative an qualitativeanalysis.

II. When the DDR is applied to ISEs based on a β-cyclodextrin, the ionic drugs assayed seem to betransported across the membrane following twodifferent processes.

THANK YOU FOR YOUR ATTENTIONTHANK YOU FOR YOUR ATTENTION

Comunicacion oral eseac_2010 [modo de compatibilidad]

Technology

Transcript of Comunicacion oral eseac_2010 [modo de compatibilidad]