Fundamentals and Applications of Chemical Sensors - ACS Publications

22 Design of Sensitive Drug Sensors: Principles and Practice Downloaded by KTH ROYAL INST OF TECHNOLOGY on September 16, 2015 | http://pubs.acs.org Publication Date: May 29, 1986 | doi: 10.1021/bk-1986-0309.ch022

R. P. Buck and V. V. Cosofret Department of Chemistry, University of North Carolina, Chapel Hill, NC 27514

Design principles of new sensors for ionic drugs follow from application of potential generation theory using three ions: Μ , X and Υ , or Μ , Ν and Y . Studies of liquid/liquid interface transport identify single-ion free energies of partition as the figures of merit for selectivity and sensitivity. New liquid membranes with sensitivities to 10 mol/1 for bisquaternary muscle relaxants and phenytoin serve as examples. +

-

-

+

+

-

-7

The s o - c a l l e d " t r a p p e d s i t e s " o f c l a s s i c a l m o b i l e - s i t e , l i q u i d i o n exchanger e l e c t r o d e s belong t o a c a t e g o r y o f compounds known as i o n a s s o c i a t i o n e x t r a c t a n t s . Examples are l o n g - c h a i n d i e s t e r s o f p h o s p h o r i c a c i d and t r i c a p r y l y l m e t h y l a m m o n i u m ( A l i q u a t ) i o n s . The l a t t e r c a t i o n was s t u d i e d e x t e n s i v e l y by F r e i s e r and co-workers ( 1 3) i n the d e s i g n o f a n i o n s e n s o r s . I n 1970 H i g u c h i , e t a l . (4) and L i t e a n u (5) i n t r o d u c e d l i q u i d membrane e l e c t r o d e s r e s p o n s i v e both t o o r g a n i c and i n o r g a n i c i o n s . These e l e c t r o d e s s'eemed t o be n e i t h e r c o n v e n t i o n a l i o n exhangernor n e u t r a l c a r r i e r - b a s e d . At the 1973 IUPAC I n t e r n a t i o n a l Symposium on I o n - S e l e c t i v e E l e c t r o d e s , J . R. C o c k r e l l , J r . p r e s e n t e d an u n p u b l i s h e d example o f a l i q u i d membrane r e s p o n s i v e t o both c a t i o n s and a n i o n s , not u n l i k e responses o f s i l v e r h a l i d e membranes. C a t i o n o r a n i o n response depended on which common i o n of the membrane was i n e x c e s s , i n s o l u b l e form, i n s o l u t i o n . A membrane c o n t a i n i n g a d e t e r g e n t i o n p a i r was r e s p o n s i v e t o e i t h e r cat i o n i c o r a n i o n d e t e r g e n t s p e c i e s i n s o l u t i o n , depending on which was i n e x c e s s . At that t i m e , t h i s e f f e c t seemed anomalous. A l t h o u g h the e q u i l i b r i u m p r i n c i p l e was a v a i l a b l e ( e q u a l i t y o f e l e c t r o c h e m i c a l p o t e n t i a l o f each i o n t h a t r e v e r s i b l y e q u i l i b r a t e s a c r o s s an i m m i s c i b l e l i q u i d / l i q u i d i n t e r f a c e ) , the elementary theory and consequences were not e x p l o r e d u n t i l r e c e n t l y ( 6 ) . To develop an i n t e r f a c i a l p o t e n t i a l d i f f e r e n c e (pd) a t a l i q u i d i n t e r f a c e , two ions Μ , X t h a t p a r t i t i o n are r e q u i r e d . However, 0097-6156/86/0309-0363$06.00/0 © 1986 American Chemical Society

In Fundamentals and Applications of Chemical Sensors; Schuetzle, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1986.

FUNDAMENTALS AND APPLICATIONS OF CHEMICAL SENSORS

Downloaded by KTH ROYAL INST OF TECHNOLOGY on September 16, 2015 | http://pubs.acs.org Publication Date: May 29, 1986 | doi: 10.1021/bk-1986-0309.ch022

364

t h i s c o n d i t i o n i s necessary but not s u f f i c i e n t , because the pd produced i s independent of s a l t c o n c e n t r a t i o n i n e i t h e r phase^ To develop a pd dependent s o l e l y on_a s i n g l e i o n a c t i v i t y , say Μ , t h r e e i o n s _ a r e r e q u i r e d — Μ , X and Υ , of which Y i s very o i l s o l u b l e ; X i s m a i n l y water s o l u b l e and M i s s o l u b l e i n both phases. The s a l t MY i s t y p i c a l l y an o r g a n i c i o n p a i r that may be i s o l a t e d and d i s s o l v e d i n an o r g a n i c s o l v e n t or prepared in s i t u by e x t r a c t i o n . The anion i s t y p i c a l l y p i c r a t e , t e t r a p h e n y l b o r a t e , t r i p h e n y l s t i l b e n y l b o r a t e or t e t r a b i p h e n y l b o r a t e . The s a l t MX, where X = CI p r e f e r a b l y , i s the sample whose M a c t i v i t y i s t o be measured at v a r i a b l e v a l u e s i n the aqueous phase. When MX i s v a r i e d , the i n t e r f a c i a l pd i s o v e r a l l S-shaped (mV vs l o g [ M X ] ) , but c o n t a i n s a l i n e a r s e c t i o n , the s o - c a l l e d N e r n s t i a n r e g i o n . I t i s merely an e x t e n s i o n o f these ideas t o demonstrate the c o n d i t i o n s t h a t the same membrane, c o n t a i n i n g MY, should a l s o be responsive, i n a Nernstian f a s h i o n , to Y a c t i v i t i e s i n s o l u t i o n . These c o n d i t i o n s a r e a g a i n a t h r e e - i o n s i t u a t i o n : M , Y and Ν . The s a l t NY i s the aqueous sample whose Y a c t i v i t y i s to be measured. Ν i s t y p i c a l l y a h y d r o p h i l i c i o n such as Na . When aqueous NY a c t i v i t y i s v a r i e d , the i n t e r f a c i a l pd i s a g a i n S-shaped (mV vs l o g [ N Y ] ) . These responses a r e i l l u s t r a t e d from a t h e o r e t i c a l c a l c u l a t i o n i n F i g u r e 1. The assumed e x t r a c t i o n parameters a r e g i v e n i n the l e g e n d . The s i m i l a r i t y w i t h s i l v e r h a l i d e membrane e l e c t r o d e s a r e summarized below. +

Saturated

S a l t AgBr (aq.)

P a r t i t i o n e d S a l t MY ( v e r y o i l s o l u b l e )

A n i o n Responsive +

Anion Responsive

( a q . ) N a B r ~ a t C's>K

1

^

2

+

( a q . ) N a Y ~ at C * s > C ( a q . ) MV

Sρ

Μι

C a t i o n Responsive

C a t i o n Responsive

+

(aq.)Ag NO ~ a t C's>K ^ 3 sp

2

+

(aq.)M Cl~

a t C · s>C-_,(aq. ) MY

+

+

I J ^ i s ^ h e ^ y p e r b o l i c relations (Ag )(Br~) = Κ and ( M ) ( Y ) = (M ) ( Y ) / K t h a t p r o v i d e s tjje b a s i c analogy between the two k i n d s of systems. I n the l a t t e r , Κ i s the i o n i c s a l t p a r t i t i o n c o e f f i c i e n t r e l a t i n g membrane and b a t h i n g s o l u t i o n a c t i v i t i e s at an e q u i l i b r i u m i n t e r f a c e . The l a t t e r form can a l s o be d e r i v e d f o r i n s o l u b l e s a l t membranes. However the s a l t a c t i v i t i e s (super bar q u a n t i t i e s ) a r e c o n s t a n t and so a r e hidden i n the v a l u e of the s o l u b i l i t y product Κ . sp E q u i l i b r i u m Theory +

+

Each i o n Μ ' Ν ' X and Y w i l l g e n e r a l l y have d i f f e r e n t e n e r g i e s i n water and i n an o r g a n i c phase: an e s t e r such as d i o c t y l a d i p a t e (low d i e l e c t r i c c o n s t a n t ) . The p a r t i t i o n f r e e energy AG.

= μ° i

- μ ° = -RTlnK. i

(1)

f o r the r e a c t i o n species

i(aq.) = species

i(org.)


Design of Sensitive Drug Sensors


BUCK AND COSOFRET

Added Formal C =C (M) X

M

7

I0"

6

5

4

3

2

I0" I0' I0" IO' IO' Added Formal C = C (M) N

1

IO"

10

Y

F i g u r e 1. C a l c u l a t e d response c u r v e s . Upper c u r v e response o f i f " : lower c u r v e response o f Y . See t e x t f o r v a l u e s o f t h e c o n s t a n t s K^, Κγ and Κχ.




366

i s a measure o f the i n t r i n s i c i o n i c o i l - s o l u b i l i t y , where K. i s the s i n g l e - i o n p a r t i t i t o n c o e f f i c i e n t and bars denote o r g a n i c pUase q u a n t i t i e s . For o i l s o l u b l e ( h y d r o p h o b i c ) i o n s /\G i s more n e g a t i v e and K. i s l a r g e r than f o r w a t e r - s o l u b l e ( h y d r o p h i l i c ) i o n s . I n a t y p i c a l two phase w a t e r / o r g a n i c system c o n t a i n i n g e q u i l i b r a t e d s a l t s MX and MY, some MX and MY w i l l be present i n each phase. T h i s two s a l t , t h r e e i o n system p r o v i d e s the necessary c o n d i t i o n s t o o b t a i n the upper-curve f o r the M -sensor i n F i g u r e 1. The c o n c e n t r a t i o n s i n each phase depend on the s a l t p a r t i t i o n c o e f f i c i e n t s I^K and ^ K y j w i t h mass and charge balance e q u a t i o n s to p r o v i d e the a d d i t i o n a l r e q u i r e d r e l a t i o n s h i p s . The l i n k between e n e r g i e s and e q u i l i b r i u m c o n c e n t r a t i o n s ( a c t i v i t i e s ) i s the e l e c t r o c h e m i c a l p o t e n t i a l f o r each i o n at e q u i l i b r i u m a c r o s s the interface: μ. = μ

+ RTlna. + z.F

(2)

ι +

i = M , X", Y"

(3)

= p^org.)

(4)

and μ (aq.) i

By e l i m i n a t i n g ψ between o p p o s i t e l y charged

s p e c i e s one has

(a )(a -)(org.) M +

x

Κ

2

= Ι^Κ

χ

(5)

(a +)(a -)(aq.) M

x

and (a +)(a -)(org.) M

v

2

(a +)(a -)(aq.) M

y

Since MY i s i n t e n t i o n a l l y more o i l s o l u b l e than MX, MY m a i n t a i n s v i r t u a l l y c o n s t a n t a c t i v i t y i n the o r g a n i c phase, when MX(aq.) i s v a r i e d . Only a v e r y s m a l l amount o f X appears i n the membrane because M i n the membrane i s a l r e a d y l a r g e and f i x e d by MY (Donnan E x c l u s i o n ) . However a t v e r y h i g h c o n c e n t r a t i o n s o f MX(aq.), i n c r e a s i n g amounts o f MX w i l l be e x t r a c t e d i n t o the o r g a n i c phase. I n p r i n c i p l e , a t h i g h enough MX(aq.) a c t i v i t i e s , the e x t r a c t e d MX exceeds the MY a l r e a d y p r e s e n t . T h i s i s the c o n d i t i o n o f Donnan F a i l u r e because the c o - i o n X e n t e r s the membrane a t a c o n c e n t r a t i o n comparable t o o r g r e a t e r than Y . A converse argument a p p l i e s t o the f a t e o f M i n the aqueous phase as MX(aq.) concentration i s decreased. Since MY m a i n t a i n s a v e r y low c o n c e n t r a t i o n i n w a t e r , as M X i a j . ) i s decreased below the e q u i l i b r i u m v a l u e o f MY(aq.), M (aq.) approaches the c o n s t a n t c o n c e n t r a t i o n o f MY(aq.). A c o n s t a n t i n t e r f a c i a l p o t e n t i a l i s approached t h a t i s independent o f f u r t h e r decreases i n MX(aq.). J n F i g . 1 the s i n g l e i o n p a r t i t i o n c o e f f i c i e n t s were chosen KL. = 10 , 1^ = 10 and Κγ = 10 , w i t h MY(org.) = 10" Consequently the e q u i l i b r i u m s aqueous MY c o n c e n t r a t i o n i s 10 M.


22.

367


BUCK AND COSOFRET

In the lower p a r t o f F i g u r e 1, the c o r r e s p o n d i n g two-phase, t w o - s a l t e x t r a c t i n g system i s MY, NY. The v a l u e s o f p a r t i t i o n ^ c o e f f i c i e n t s s e l e c t e d ^ f o r i l l u s t r a t i o n were, as above, = 10 , Ky 10 and K = 10 . Consequently m i r r o r image p o t e n t i a l c h a r a c t e r i s t i c s r e s u l t , and Donnan F a i l u r e occurs when NY(aq.) exceeds 1 0 - 1 0 M NY(aq.). a

N


P o t e n t i a l Theory The i n t e r f a c i a l p o t e n t i a l d i f f e r e n c e (pd) f o r the p a r t i t i o n e q u i l i b r i u m i n t e r f a c e i s g i v e n by the e q u a l i t y of e l e c t r o c h e m i c a l p o t e n t i a l i n terms o f a l l ions i n e q u i l i b r i u m , e q u a t i o n ( 4 ) . RT Αφ

= d>(org.) - d>(aq.)

Ad>

RT K a = — l n - ^ -

Κ.a.

l n - ^ (7) ζ .F a. ι ι However, f o r convenience i n c a l c u l a t i o n , the i n t e r f a c i a l pd i s determined from those s p e c i e s whose a c t i v i t i e s a r e known or e a s i l y c a l c u l a t e d . For the upper curve i n F i g u r e 1, i n the l i n e a r range MX i s predominately i n water w h i l e MY i s predominately i n the o r g a n i c phase s i n c e « Κγ. Consequently M a c t i v i t i e s a r e known and used i n e q u a t i o n /, t o g i v e +

RT + — lna +

M

F

a

= Ad)°

(8)

F

M

( N e r n s t i a n response) over a wide a c t i v i t y range. However, at very low MX a c t i v i t i e s , the pd becomes i n s e n s i t i v e to d e c r e a s i n g M a c t i v i t i e s and l e v e l s o f f at a v a l u e RT IL. I n — 2F Κγ

Ad)

(9)

w h i l e at very h i g h MX a c t i v i t i e s ( g e n e r a l l y o n l y seen when X = I , NO^ , CIO^ ) the pd a g a i n l e v e l s o f f s i n c e Donnan E x c l u s i o n by Y i s v i o l a t e d i n the o r g a n i c phase and RT IC.

Ad> 2F These l i m i t i n g , expression :

I n — Κ

(10)

χ

s i n g l e - s a l t pds a r e d e r i v e d from the more g e n e r a l

Λ

.

R T

,

Ad> = 2F —in

r M M K

a

M

+

xx x

+

K

a

/ a

/a

K

a

/ a

N N N

W V

The v a l u e s o f a c t i v i t i e s t o be used a r e those c a l c u l a t e d from e q u i l i b r i u m t h e o r y . For one s a l t , say MX


(ID

368

FUNDAMENTALS AND APPLICATIONS OF CHEMICAL SENSORS RT

/U

- K a /a +

+

+

(12)

In 2F — Κ a /a —

T h i s e q u a t i o n i s s u i t a b l e even i n the case o f unequal c o n c e n t r a t i o n s o f M and X i n each phase. However, i f o n l y MX i s p r e s e n t , a s i m p l i f i c a t i o n i s p o s s i b l e because t h e r e a r e equal c o n c e n t r a t i o n s o f + and - i o n s i n each phase.

RT Downloaded by KTH ROYAL INST OF TECHNOLOGY on September 16, 2015 | http://pubs.acs.org Publication Date: May 29, 1986 | doi: 10.1021/bk-1986-0309.ch022

Ad>

- K a /7 +

+

-

+

In 2F — Κ a /X

r-KjJ

RT

—In 2F

—

I

(13)

κ / 7

These v a l u e s a r e , i n some sense d e r i v e d from c o r r o s i o n t h e o r y , "mean" o r "mixed" p o t e n t i a l s because they a r e determined by exchange o f two charged s p e c i e s . When a c t i v i t y c o e f f i c i e n t s a r e i g n o r e d e q u a t i o n 13 reduces t o 10. By the same a n a l y s i s , a s i n g l e s a l t MY p a r t i t i o n e d g i v e s a constant p o t e n t i a l i n e q u a t i o n 9. These two l i m i t i n g v a l u e s a r e shown i n F i g u r e 1 p o i n t s A and E. L i k e w i s e , Donnan F a i l u r e upon a d d i t i o n o f excess a q . NY g i v e s a constant negative l i m i t of RT (14) 2F D e t a i l s o f the c u r v a t u r e r e g i o n s i n F i g u r e 1 have been g i v e n i n reference (6). S e n s i t i v i t y and S e l e c t i v i t y +

The lower d e t e c t i o n l i m i t f o r i o n s M o r Y i s o f t e n g i v e n as the i n t e r s e c t i o n o f the N e r n s t i a n r e g i o n w i t h the l i m i t i n g p o t e n t i a l o f e q u a t i o n 9. T h i s v a l u e depends on the membrane l o a d i n g MY(org.) and i s g i v e n by a (limit) ι v

a (limit) M w

(15)

M 6

which i s 1θ"~ Μ M* i n F i g u r e 1. The t o t a l range o f a v a i l a b l e p o t e n t i a l s f o r M measurements i s determined by the two l i m i t i n g p o t e n t i a l s o f e q u a t i o n s 9 and 10. T h i s i s the s o - c a l l e d "window" for M RT Κγ /\ (window) = — I n — 2F Κ There i s a l s o a window f o r Y

measurement,


(16)

22.


BUCK A N D COSOFRET

369

The d e f i n i t i o n o f s e l e c t i v i t y o f the e l e c t r o d e f o r two ions o f the same s i g n r e q u i r e s c o n s i d e r a t i o n o f the responses t o MX and I X , when the membrane i s i n i t i a l l y loaded w i t h MY. M i s the p r i n c i p a l i o n and I i s the i n t e r f e r e n c e . D e f i n i n g the f r a c t i o n f as


(17)

then i o n exchange e q u i l i b r i u m r e q u i r e s i n the membrane w i t h a c t i v i t i e s

=

V a

I +

V

Y ) F / ( 1

f o r m a t i o n o f both MY and IY

+

(18)

£ )

= Xjm/u + f )

(19)

Consequently the i n t e r f a c i a l pd i s r e l a t e d t o both a^+ and a c c o r d i n g to

/U = ^lnF

" 7 w M A L

VM *

+

(20)

A

M

The i n t e r f a c i a l pd s e l e c t i v i t y c o e f f i c i e n t , the f a c t o r m u l t i p l y i n g a^. i s determined by the r a t i o K J / K ^ J by the a c t i v i t y c o e f f i c i e n t r a t i o , and by the m o b i l i t y r a t i o , when the i n t e r n a l d i f f u s i o n p o t e n t i a l c o n t r i b u t i o n i s added. C l e a r l y i n t e r f e r e n c e s s h o u l d c o r r e l a t e w i t h the r a t i o Κ / I L , which can be determined from salt extraction coefficients J / M ^ X f° series of p o s i t i v e d r u g s , u s i n g common a n i o n s a l t s . T h i s r e s u l t i s w e l l documented i n the l i t e r a t u r e ( 7 , 8 ) . A c u r i o u s c o r r e l a t i o n f o r N-based drugs s t u d i e d by us and by F r e i s e r (£) i s a t r e n d i n s e l e c t i v i t y k

K

ra

R

X

RNH

3

< R NH 2

2

< R NH 3 0

+

< R,N 4

+

i n which q u a r t e r n a r y drugs o f the same carbon number a r e most s e n s i t i v e l y detected. Omitted from t h i s elementary theory a r e e f f e c t s o f p l a s t i c i z e r and i o n p a i r i n g . Ion p a i r f o r m a t i o n c o n s t a n t s i n the o r g a n i c phase i n c r e a s e w i t h d e c r e a s i n g d i e l e c t r i c c o n s t a n t s o f the p l a s t i c i z e r , i n the absence o f s p e c i f i c bonding e f f e c t s . I n the more g e n e r a l t h e o r y the s i n g l e i o n p a r t i t i o n c o e f f i c i e n t s a r e r e p l a c e d by the product of p a r t i t i o n c o e f f i c i e n t and i o n p a i r f o r m a t i o n c o n s t a n t . Experimental:

Reagents

A l l r e a g e n t s , except TPSB ( t r i p h e n y l s t i l b e n y l b o r a t e ) , were o f a n a l y t i c a l - r e a g e n t grade and were used as r e c e i v e d . S u c c i n y l c h o l i n e c h l o r i d e , hexamethonium bromide and decamethonium bromide were purchased from Sigma ( S t . L o u i s , MO). NPOE ( 2 n i t r o p h e n y l o c t y l e t h e r ) ( F l u k a ) and p o l y ( v i n y l c h l o r i d e ) ( A l d r i c h )



370


were used. T r i p h e n y l s t i l b e n y l b o r a t e ( p o t a s s i u m s a l t ) was k i n d l y donated by Dr. D. D a n i e l s (Kodak, R o c h e s t e r , NY). Injectable s u c c i n y l c h o l i n e c h l o r i d e s o l u t i o n s (USP q u a l i t y ) were purchased from a l o c a l d r u g s t o r e . A l l c a t i o n drug s o l u t i o n s were prepared w i t h d i s t i l l e d water i n a T r i s - H C l b u f f e r o f pH 7.0. S u c c i n y l c h o l i n e s o l u t i o n s c o n t a i n e d 0.05% (w/v) methyl-j>hydroxybenzoate as s t a b i l i z e r . P h e n y t o i n (sodium s a l t ) and decanol were s u p p l i e d by Sigma ( S t . L o u i s , MO); o t h e r m a t e r i a l s were t r i c a p r y l y l m e t h y l a m m o n i u m c h l o r i d e o r A l i q u a t 336S (General M i l l s C h e m i c a l s , I n c . , Kankakee, I L ) . S o l u t i o n s o f sodium p h e n y t o i n were prepared by s e r i a l d i l u t i o n w h i l e k e e p i n g both pH and i o n i c s t r e n g t h a t c o n s t a n t v a l u e s , 10 and 0.1 mol/1, r e s p e c t i v e l y . The s e l e c t i v i t y c o e f f i c i e n t s were determined at pH 10.0 and 0.1 mol/1 i o n i c s t r e n g t h , both a d j u s t e d w i t h borax-NaOH b u f f e r s o l u t i o n o f pH 10.0. Experimental:

Electroactive

Materials

B i s q u a t e r n a r y , as w e l l as monoquaternary compounds and v a r i o u s amino d e r i v a t i v e s , r e a c t w i t h t e t r a p h e n y l b o r a t e and s i m i l a r compounds t o form s t a b l e i o n - p a i r complexes. TPSB was found to be v e r y s u i t a b l e as an i o n - p a i r i n g agent f o r b i s q u a t e r n a r y drugs w i t h which i t forms v e r y i n s o l u b l e compounds. The TPSB complexes were p r e p a r e d i n s i t u , by s o a k i n g the TPSB ( p o t a s s i u m s a l t ) / P V C membranes i n the a p p r o p r i a t e b i s q u a t e r n a r y s o l u t i o n . Of the p l a s t i c i z e r s t e s t e d , 2 - n i t r o p h e n y l o c t y l e t h e r (NPOE), d i o c t y l p h t h a l a t e , d i - i s o - b u t y l p h t h a l a t e , n i t r o b e n z e n e , 2-nitro-j>cyraene, NPOE showed the best b e h a v i o r i n terms o f response time and r e p r o d u c i b i l i t y . The membrane c o m p o s i t i o n s were 3.2% (w/w) TPSB, 64.5% (w/w) NPOE and 32.3% (w/w) PVC. The q u a t e r n a r y ammonium c a t i o n , t r i c a p r y l y l m e t h y l a m m o n i u m , i s a w e l l known i o n - p a i r i n g e x t r a c t i n g agent and was used t o o b t a i n the i o n - p a i r a s s o c i a t i o n complex w i t h 5 , 5 - d i p h e n y l h y d a n t o i n a t e a n i o n . The i o n - p a i r complex was embedded i n a PVC m a t r i x , c o n t a i n i n g NPOE as p l a s t i c i z e r . The membrane c o m p o s i t i o n was 7.7% (w/w) e l e c t r o a c t i v e m a t e r i a l , 61.5% (w/w) NPOE and 30.8% (w/w) PVC. F i v e grams o f A l i q u a t 336S were mixed w i t h 5.0 g o f decanol and e q u i l i b r a t e d w i t h ten s e p a r a t e 15 ml a l i q u o t s o f 0.1 mol/1 sodium p h e n y t o i n s o l u t i o n i n 20% (v/v) m e t h a n o l . The o r g a n i c phase was washed t w i c e w i t h d i s t i l l e d water and then c e n t r i f u g e d u n t i l a c l e a r s o l u t i o n was o b t a i n e d . Experimental:

Construction

of Electrodes

The b a s i c p r i n c i p l e o f the e l e c t r o d e c o n s t r u c t i o n has been d e s c r i b e d elsewhere ( 1 0 ) . The e l e c t r o a c t i v e m a t e r i a l (50 mg) was w e l l mixed w i t h 400 mg p l a s t i c i z e r (NPOE) and l a t e r w i t h 200 mg PVC powder d i s s o l v e d i n 6 ml o f t e t r a h y d r o f u r a n . The c l e a r l i q u i d was poured i n t o a 28 mm i . d . g l a s s r i n g on as sheet o f p l a t e g l a s s . A pad o f f i l t e r paper p l a c e d on top o f the r i n g was kept i n p l a c e by a heavy m e t a l l i c weight and the assembly l e f t f o r 48 h r s . t o a l l o w slow s o l v e n t e v a p o r a t i o n . A d i s c (0.9 cm d i a m e t e r ) was cut from the membrane and f i x e d t o the end o f a 10 mm Tygon tube by u s i n g a P V C - t e t r a h y d r o f u r a n s o l u t i o n as a d h e s i v e . The o t h e r end o f the Tygon tube was f i t t e d on t o a g l a s s tube to form the e l e c t r o d e


22.

BUCK AND COSOFRET

371



body. A s i l v e r / s i l v e r c h l o r i d e w i r e was then i n s e r t e d and the e l e c t r o d e body was f i l l e d w i t h t y p i c a l l y 0.01 NaCl, s a t u r a t e d w i t h A g C l and a s a l t o f exchanging i o n and^a b u f f e r s o l u t i o n . The i n t e r n a l r e f e r e n c e s o l u t i o n s were 10 M o f the r e s p e c t i v e c a t i o n drug at pH 7.0 (0.1 M T r i s - H C l b u f f e r ) . The TPSB i n the polymer membranes was converted t o the b i s q u a t e r n a r y - d r u g form by s o a k i n g the e l e c t r o d e s i n the a p p r o p r i a t e 10 M drug f o r 24 h. When not i n use, the e l e c t r o d e s were s t o r e d i n the same s o l u t i o n as the i n t e r n a l s o l u t i o n . For the a n i o n d r u g , the body was f i l l e d w i t h 10 3 mol/1 sodium p h e n y t o i n s o l u t i o n o f pH 10.0 (borax-NaOH b u f f e r ) . Results Although t h i s theory has not been s u c c i n c t l y r e p o r t e d u n t i l r e c e n t l y , i n t u i t i v e a p p l i c a t i o n s have been a p p l i e d e a r l i e r . R u z i c k a , et a l . (11) i n c r e a s e d the o i l s o l u b i l i t y gf phosphate e s t e r anions t o i n c r e a s e the s e n s i t i v i t y o f the Ca electrode. Gavach, et a l . U_2) and B i r c h , e t a l . (13) made d e t e r g e n t sensors f o r c a t i o n s and a n i o n s . The e l e c t r o d e s d e s c r i b e d above show n e a r - N e r n s t i a n responses over a l a r g e range on c o n c e n t r a t i o n s and v e r y low d e t e c t i o n l i m i t s . These e l e c t r o d e s a r e not a f f e c t e d by pH i n the range 2-10. T h e i r s e l e c t i v i t i e s r e l a t i v e t o a number o f i n o r g a n i c i o n s , amino a c i d s , n e u r o t r a n s m i t t e r s , drugs and v a r i o u s d r u g - e x c i p i e n t s a r e outstanding. Response c h a r a c t e r i s t i c s a r e g i v e n i n Tables I and II. E x t e n s i v e s e l e c t i v i t y t a b l e s a r e g i v e n i n r e c e n t or f o r t h c o m i n g p u b l i c a t i o n s (14,15).

T a b l e I . Response C h a r a c t e r i s t i c s f o r B i s q u a t e r n a r y - d r u g Electrodes Parameter

a

S l o p e ( m V / l o g a) Intercept(mV)

Succinylcholine Electrode 29.05±0.35 157±1.8

6

iQ-l-io"

U s a b l e range(M)

-2 -7 10 — 1 0

Detection limit(M) (ng m l " )

1.58xl0~ 46

a

7

152±2.1

10"—2.5xl0~

7

10"—5.0xl0"

6

3.16xl0" 6.4

Decamethonium Electrode 29.45±0.29

28.03±0.44 14712.2

b

L i n e a r range(M)

1

Hexamethonium Electrode

Membrane

8

10"—2.5xl0" -2 -7 10 — 1 0 1.12xl0" 29

7

A v e r a g e v a l u e s c a l c u l a t e d f o r 10 — 1 0 M range w i t h s t a n d a r d d e v i a t i o n o f average s l o p e v a l u e f o r m u l t i p l e c a l i b r a t i o n ( 5 - 7 ) .

^ S t a n d a r d d e v i a t i o n o f v a l u e s r e c o r d e d d u r i n g one month. Source: Reproduced w i t h p e r m i s s i o n from R e f . 14. C o p y r i g h t 1984 E l s e v i e r (Amsterdam).


7

372


Table II.

Response Characteristics for the Phenytoin-Membrane Electrode


Parameter Slope(mV/log a) Intercept(mV) Linear Range(mol/1) Useable Range(mol/1) Detection Limit(mol/1) (yg/ml)

56.25 + 0.83a 182 + 2.1b ί ο " 1 — io" 5 i o - 1 — io~5 1.5 χ 10"5 4.1

Standard deviation of average slope value for multiple calibrations in the 10*" ^—10"""* mol/1 range. Standard deviation of values recorded during one month.

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Coetzee, C. J.; Freiser, H. Anal. Chem. 1968, 40, 2071. Coetzee, C. J.; Freiser, H. Anal. Chem. 1969, 41, 1128. James, H. J.; Carmack, G. P.; Freiser, H. Anal. Chem. 1972, 44, 853. Higuchi, T.; Illian, C. R.; Tossounian, J. L. Anal. Chem. 1970, 42, 1674. Liteanu, C.; Hopirtean, E. Talanta 1970, 17, 1067. Melroy, O. R.; Buck, R. P. J. Electroanal. Chem. 1973, 143, 23. Koryta, J. "Ion-Selective Electrodes"; Cambridge Univ. Press: Cambridge, 1975, Chapt. 6. Koryta, J.; Stulik, K. "Ion-Selective Electrodes"; Cambridge Univ. Press: Cambridge, 1983, Chapt. 7. Freiser, H., personal communication. Moody, G. J.; Oke, R. B.; Thomas, J. D. R., Analyst 1970, 95, 910. Ruzicka, J.; Hansen, E. H.; Tjell, J. C. Anal. Chim. Acta. 1973, 67, 155. Gavach, C.; Seta, P. Anal. Chim. Acta. 1970, 50, 407. Birch, B. J.; Clarke, D. E. Anal. Chim. Acta. 1973, 67, 387. Cosofret, V.V.; Buck, R. P., Anal. Chim. Acta. 1984, 162, 357. Cosofret, V. V.; Buck, R. P., J. Pharm. Biomed. Anal. 1984 in press.

RECEIVED

October 31,

1985


Fundamentals and Applications of Chemical Sensors - ACS Publications

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