Salicylate-selective electrodes based on Al(III) and Sn(IV) salophens

Article abstract of DOI:10.1021/ac990749w

New salicylate-selective electrodes based on aluminum(III) and tin(IV) salophens are described. The electrodes were prepared by incorporating the ionophores into plasticized poly(vinyl chloride) (PVC) membranes, which were directly coated on the surface of graphite electrodes. These novel electrodes display high selectivity for salicylate with respect to many common inorganic and organic anions. The influence of membrane composition and pH and the effect of lipophilic cationic and anionic additives on the response properties of the electrodes were investigated. The electrode based on- aluminum salophen, with 32% PVC, 65.8% plasticizer, and 2.2% ionophore, shows the best potentiometric response characteristics and displays a linear log [Sal^-] vs EMF response over the concentration range 1 x 10^-6-1 x 10^-1 M in phosphate buffer solutions of pH 7.0, with a Nernstian slope of -59.2 mV/decade of salicylate concentration. Highest selectivity was observed for the membrane incorporating 38.8% PVC, 57.3% plasticizer, 2.6% Sn(salophen), and 1.3% sodium tetraphenylborate. The electrodes exhibit fast response times and micromolar detection limits (~1 x 10^-6 M salicylate) and could be used over a wide pH range of 3-8. Applications of the electrodes for determination of salicylate in pharmaceutical preparations and biological samples are reported.

Full text of DOI:10.1021/ac990749w

Anal. Chem. 2000, 72, 956-962
S a lic yla t e -S e le c t ive Ele c t ro d e s Ba s e d o n Al(III)
a n d S n (IV) S a lo p h e n s
Sa id Sha hrokhia n, Moha m m a d K. Am ini,* Re za Kia , a nd Sha hra m Ta nge s ta nine ja d
Department of Chemistry, University of Isfahan, Isfahan 81744, Iran
New salicylate-selective electrodes based on aluminum-
III) and tin(IV) salophens are described. The electrodes
the lipophilicity of the anions, with more lipophilic anions respond-
ing the best. One of the most important recognition elements that
can be utilized in the development of ISEs involves specific metal-
(
were prepared by incorporating the ionophores into
plasticized poly(vinyl chloride) (P VC) membranes, which
were directly coated on the surface of graphite electrodes.
These novel electrodes display high selectivity for salicy-
late with respect to many common inorganic and organic
anions. The influence of membrane composition and pH
and the effect of lipophilic cationic and anionic additives
on the response properties of the electrodes were inves-
tigated. The electrode based on aluminum salophen, with
6
ligand interactions. For the development of a truly anion-selective
electrode, a strong interaction between the ionophore and the
anions is required in order to complex anions in a selective
fashion. Complexes of several metal ions with different ligands,
such as phthalocyanines,7,8 porphyrins,9,10 and metallocenes,11 as
ionophores for anions, have been observed to show such specific
metal-ligand interactions and induce anion selectivities in the
membranes that differ somewhat from the classical anion ex-
changers. Potentiometric response of the membranes doped with
these complexes is believed to be based on the coordination of
analyte anions as an axial ligand to the metal center of the carrier
molecule.
The purpose of the present work has been the development
of salicylate-selective electrodes based on poly(vinyl chloride)
(PVC) membranes of aluminum and tin salophens, coated on the
surface of graphite electrodes. Salicylic acid is one of the common
metabolites of acetylsalicylic acid (aspirin), which is widely used
as an analgesic and inflammatory agent and, recently, also as a
preventive of heart attacks.12 It is easily hydrolyzed to salicylic
acid, which circulates in blood in the ionized form. Monitoring
the plasma salicylate concentration is important for controlling
the dose and frequency of aspirin administration. The free acid is
widely used as an antiseptic and a preservative for foods. In recent
years, the electrochemical properties and preparations of several
3
2 % P VC, 6 5 .8 % plasticizer, and 2 .2 % ionophore, shows
the best potentiometric response characteristics and
-
displays a linear log [Sal ] vs EMF response over the
-
6
-1
concentration range 1 × 1 0 -1 × 1 0 M in phosphate
buffer solutions of pH 7 .0 , with a Nernstian slope of
-5 9 .2 mV/ decade of salicylate concentration. Highest
selectivity was observed for the membrane incorporating
3
1
8 .8 % P VC, 5 7 .3 % plasticizer, 2 .6 % Sn(salophen), and
.3 % sodium tetraphenylborate. The electrodes exhibit
fast response times and micromolar detection limits ( ∼1
-
6
×
1 0 M salicylate) and could be used over a wide pH
range of 3 -8 . Applications of the electrodes for determi-
nation of salicylate in pharmaceutical preparations and
biological samples are reported.
Potentiometric detection based on ion-selective electrodes
(
ISEs), as a simple method, offers great advantages such as speed
new salicylate-selective membrane electrodes have been reported
by using a variety of ion carriers.1
3-18
The development of a
and ease of preparation and procedures, relatively fast response,
reasonable selectivity, wide linear dynamic range, and low cost.
These characteristics have inevitably led to sensors for several
ionic species, and the list of available electrodes has grown
substantially over the past years.1
A very interesting development of potentiometric sensors is
in the construction of electrodes that respond selectively to
biological compounds. The wide use of ISEs in routine chemical
and biochemical analysis has been accompanied by a search for
ionophores that can chemically recognize specific ions and offer
either new or improved selectivities for different ions. In many
instances in the literature, the membranes used in anion-selective
sensors are based on quaternary ammonium or phosphonium
salts.2 Selectivity of these classical ion exchangers depends on
(
(
4) Yu, R. Q. Ion-Sel. Electrode Rev. 1 9 8 6 , 3, 153-171.
5) Wotring, V. J.; Johnson, D. M.; Bachas, L. G. Anal. Chem. 1 9 9 0 , 62, 2,
506-1510.
(6) Hutchins, R. S.; Bachas, L. G. Anal. Chem. 1 9 9 5 , 67, 1654-1660.
1
(
(
(
7) Li, J. Z.; Wu, X. C.; Yuan, R.; Lin, H. G.; Yu, R. Q. Analyst 1 9 9 4 , 119, 1363-
368.
8) Nakamura, T.; Hayashi, C.; Ogawara, T. Bull. Chem. Soc. Jpn. 1 9 9 6 , 69,
1555-1559.
1
9) Bakker, E.; Malinowska, E.; Schiller, R. D.; Meyerhoff, M. E. Talanta 1 9 9 4 ,
4
1, 881-890.
(
(
(
10) Chaniotakis, N. A.; Park, S. B.; Meyerhoff, M. E. Anal. Chem. 1 9 8 9 , 61,
566-570.
11) Hisamoto, H.; Siswanta, D.; Nishihara, H.; Suzuki, K. Anal. Chim. Acta 1995,
3
04, 171-176.
12) Reiman, A. N. Engl. J. Med. 1 9 8 8 , 318, 245-246.
-5
(13) Chang, Q.; Meyerhoff, M. E. Anal. Chim. Acta 1 9 8 6 , 186, 81-90.
14) Hassan, S. S. M.; Hamada, M. A. Analyst 1 9 8 8 , 113, 1709-1713.
(
(
(
1) B u¨ hlmann, P.; Pretsh, E.; Bakker, E. Chem. Rev. 1 9 9 8 , 98, 1593-1687.
2) Wegmann, D.; Weiss, H.; Ammann, D.; Morf, W. E.; Pretsch, E.; Sugahara,
K.; Simon, W. Microchim. Acta 1 9 8 4 , 3, 1-16.
(15) Hutchins, R. S.; Bansal, P.; Molina, P.; Alajarin, M.; Vidal, A.; Bachas, L. G.
Anal. Chem. 1 9 9 7 , 62, 1273-1278.
(16) Li, Z. Q.; Song, X. P.; Shen, G. L.; Yu, R. Q. Anal. Lett. 1 9 9 8 , 31, 1473-
1486.
(
3) Arnold, M. A.; Solsky, R. L. Anal. Chem. 1 9 8 6 , 58, 84R-101R.
956 Analytical Chemistry, Vol. 72, No. 5, March 1, 2000
10.1021/ac990749w CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/03/2000

suitable salicylate-selective sensor, would enable the detection of
free” salicylate in samples and could aid researchers in studying
spectrum in which hydrogen bonding occurs. The resonance of
OH protons, which appears at δ 13.0 in the free salophenH
“
2
the pharmacological role of this drug.10 The proposed membrane
electrodes based on metallosalophens display a low detection limit
and high selectivity and sensitivity to salicylate determination and
is promising for measurement of salicylate in biological samples.
spectrum and is broad owing to intramolecular exchange, is absent
in spectra of the complexes.
A stock solution of salicylate, 0.1 M, was prepared by dissolving
1.601 g of sodium salicylate in 100 mL of water. Solutions of
interferences, 0.1 M, were prepared by dissolving the appropriate
amount of each compound, usually their sodium salts, in water.
Working solutions were prepared by successive dilutions with
water. All of the working solutions were buffered at pH 7.0, using
0.05 M phosphate buffer solution.
For the preparation of pharmaceutical samples, tablets of three
different samples of aspirin were finely powdered. A precisely
weighed portion of each sample was refluxed with ∼50 mL of 0.5
M NaOH for 1 h. After being filtered, the solution was diluted to
250 mL in a volumetric flask and used for the determination of
salicylate content by potentiometric and spectrophotometric
methods.
EXPERIMENTAL SECTION
Reagents. Poly(vinyl chloride) of high relative molecular
weight, dioctyl phthalate (DOP), trioctylmethylammonium chlo-
ride (TOMACl), and sodium tetraphenylborate (NaTPB) were
used as received from Aldrich. Tetrahydrofuran (THF) and all
other chemicals were of the highest purity available from Merck
and were used without further purification, except THF, which
was distilled before use. All aqueous solutions were prepared with
deionized, distilled water.
The complexes, N,N′-bis(salicylidene)-1,2-phenylenediamino-
aluminum(III) nitrate [Al(salophen)], and its corresponding tin-
(
IV) chloride [Sn(salophen)] (general structural formula I), were
P reparation of Electrodes. Electrodes were prepared from
spectroscopic-grade graphite rods (3 mm diameter and 10 mm
long). The graphite rod was sealed into the end of a PVC tube of
about the same diameter by epoxy cement. Electrical contact was
made by attaching a shielded copper wire, via silver-loaded epoxy
cement, into the back of the graphite rod. The working surface
of the electrode was polished with fine alumina slurries on a
polishing cloth, ultrasonicated in distilled water, and allowed to
dry.
I
Membrane solutions were prepared by dissolving varying
amounts of the ion active phase (aluminum or tin salophen),
together with appropriate amounts of DOP (as plasticizer) and
PVC, to give a total mass of 200 mg, in ∼5 mL of THF. NaTPB
and TOMACl as lipophilic anionic and cationic additives were also
incorporated in some of the mixtures. Membrane compositions
are listed in Table 1. The polished graphite electrode was dipped
into the membrane solution several times, and the solvent was
evaporated each time. A membrane was formed on the graphite
surface, and the electrode was allowed to set overnight.
P otential Measurements. The electrodes were equilibrated
for 24 h in 0.05 M salicylate solution. The potential measurements
were carried out at 25 ( 1 °C with a digital pH/ mV meter (Jenway
model 3305) by setting up the following cell assembly:
synthesized by modification of the reported procedures,1
9-22
as
follows: 1,2-Phenylenediamine, 0.54 g (5.0 mmol), was dissolved
in 25 mL of ethanol and then transferred into a 250-mL three-
necked flask. Under reflux, 1.22 g (10.0 mmol) of salicylaldehyde
in 25 mL of ethanol was added dropwise to the flask. The stirred
mixture was kept reacting for 45 min, under reflux, and then
cooled to room temperature. The solid mass was filtered, and the
2
product, N,N′-bis(salicylidene)-1,2-phenylenediamine (salophenH ),
was recrystallized from ethanol and vacuum-dried for 12 h: 1H
NMR δ 6.8-7.6 (m, 12H, phenyl), 8.8 (s, 2H, -CHdN-), 13.0
-
1
(
1
s, 2H, OH); IR (ν, cm ) 1620 s, 1590 s, 1550 s, 1475 s, 1450 s,
290 s, 1210 m, 1150 m, 1120 w, 1020 m, 930 m, 830 m, 750 s, and
a very broad band at 3000 cm-1. To a 1.58-g (5.0 mmol) sample
of salophenH in 50 mL of ethanol was added 1.13 g (5.0 mmol)
of SnCl ‚2H O or 1.88 g (5.0 mmol) of Al(NO ‚9H O in 30 mL
Hg, Hg Cl2(S),
2
2
KCl (satd) | sample solution | membrane | graphite surface
2
2
3
)
3
2
of ethanol, drop by drop. After being stirred for 1 h at room
temperature, the mixture was refluxed for 2 h and cooled to room
temperature, and the bright yellow Al(salophen) or the orange
product of Sn(salophen) was filtered, washed with ethanol and
hot water several times, and dried under vacuum at 100 °C.
There is no obvious frequency corresponding to ν(OH) in the
IR spectra of the complexes as in the case of the free ligand
The pH of the sample solutions was monitored simultaneously
with a conventional glass pH electrode. Calibration curves were
constructed by plotting the potential, E, vs the logarithm of the
concentration of salicylate at constant pH.
RESULTS AND DISCUSSION
P otentiometric Response Characteristics of Electrodes.
(
(
(
(
17) Li, J. Z.; Pang, X. Y.; Gao, D.; Yu, R. Q. Talanta 1 9 9 5 , 42, 1775-1781.
18) Katsu, T.; Mori, Y. Talanta 1 9 9 6 , 43, 755-759.
19) Atwood, D. A.; Jegier, J. A.; Rutherford, D. Inorg. Chem. 1 9 9 6 , 35, 63-70.
20) Mao, L.; Tian, Y.; Shi, G.; Liu, H.; Jin, L.; Yamamoto, K.; Tao, S.; Jin, J.
Anal. Lett. 1 9 9 8 , 31, 1991-2007.
The potentiometric response characteristics of the plasticized PVC-
based membrane electrodes, incorporating Al(salophen) or Sn-
(salophen) ionophores, toward salicylate, in buffer solutions of
pH 7.0, are shown in Figures 1 and 2, respectively. The electrodes
based on both ionophores generated stable potential responses
in a solution containing salicylate after conditioning for ∼24 h.
(
(
21) Marzilli, L. G.; Marzilli, P. A.; Halpern, J. J. Am. Chem. Soc. 1 9 7 1 , 93, 1374-
1
378.
22) Chen, D.; Martell, A. E. Inorg. Chem. 1 9 8 7 , 26, 1026-1030.
Analytical Chemistry, Vol. 72, No. 5, March 1, 2000 957

Ta b le 1 . Va ria t io n o f P o t e n t io m e t ric Re s p o n s e Ch a ra c t e ris t ic s o f Ele c t ro d e s Ba s e d o n Alu m in u m a n d Tin
S a lo p h e n s w it h Diffe re n t Me m b ra n e Co m p o s it io n s , Me a s u re d in P h o s p h a t e Bu ffe r S o lu t io n s (p H 7 .0 )
%
(w/ w) of various components
electrode
PVC
DOP
Al(salophen)
TOMACl
NaBPh4
slope (mV/ decade)
linear range (M)
detection limit (M)
-
6
-1
-1
-1
-1
-6
A
B
C
D
E
F
31.9
32.0
31.8
38.9
38.0
37.9
62.6
65.8
66.8
58.5
58.2
58.2
5.5
2.2
1.4
2.6
2.7
2.9
-56.0
-59.2
-50.2
-58.9
1 × 10 -1 × 10
1 × 10
-
6
-6
1 × 10 -1 × 10
1 × 10
-
5
-6
1 × 10 -1 × 10
2 × 10
-
6
-6
5 × 10 -1 × 10
2.5 × 10
1.1
1.0
-58.9
1 × 10-6-1 × 10-1
1 × 10-6
Sn(salophen)
-
5
-1
-1
-1
-1
-1
-6
G
H
I
J
K
33.1
32.0
39.2
38.8
38.5
64.8
63.0
58.2
57.3
57.6
2.1
5.0
2.6
2.6
2.8
-59.0
-58.3
-58.7
-57.0
-57.2
1 × 10 -1 × 10
4 × 10
-
4
-4
1 × 10 -1 × 10
1 × 10
-
5
-6
5 × 10 -1 × 10
3 × 10
-
5
-5
1.3
1 × 10 -1 × 10
1 × 10
-
6
-7
1.1
1 × 10 -1 × 10
8 × 10
Fig u re 1 . Potentiometric response of different electrodes based on
Fig u re 2 . Potentiometric response of different electrodes based on
Al(salophen). Compositions of electrodes are summarized in Table
Sn(salophen). Compositions of electrodes are summarized in Table
1.
1.
After such a treatment, a Nernstian response was obtained for
some of the electrodes in salicylate solutions of different concen-
trations, and the slope remained almost constant. Some of the
electrodes displayed remarkable selectivity for salicylate over most
common anions.
of the ion active phase in both membranes results in electrodes
that display somewhat smaller slopes. The incorporation of
TOMACl, as a cationic additive to the membranes, had no
significant effect on the sensitivity of the Al(salophen)-based
electrode, but decreased the slope of the calibration graph for
the Sn(salophen) electrodes, and, as will be discussed later in
this paper, worsened the selectivities of the membranes based
on both ionophores. The influence of the lipophilic anionic additive
on the potentiometric response of the electrodes based on both
ionophores was also investigated. Without this additive, the
membranes already exhibited Nernstian responses toward sali-
cylate (electrodes B and G). In the case of the Al(salophen)
membrane, addition of NaTPB dramatically worsened the re-
sponse of the electrode (electrode E), so that the electrode no
longer responded to anions. For the membrane containing Sn-
(salophen), in the presence of NaTPB (electrode J), the slope of
the calibration plot was slightly decreased, but as will be seen
later in this paper, the selectivity was greatly improved.
It is well known that the sensitivity, linear dynamic range, and
selectivity obtained for a given sensor depend significantly on the
membrane composition. The effect of membrane composition on
the electrode performance was studied by varying the ratio of the
membrane active phase, PVC, and DOP. Additionally, we prepared
membranes with TOMACl and NaTPB as cationic and anionic
additives. Table 1 presents the compositions of several typical
membranes, along with their other characteristics. The potential
response of all the membrane sensors was studied in the
-
7
-1
concentration range 1 × 10 -1 × 10 M salicylate. As can be
seen in Figures 1 and 2 and Table 1, an increase in the
concentration of the membrane active phase, up to ∼2.2% for both
ionophores, is beneficial for obtaining any electrode slope closer
to the theoretical value. Further increase in the concentration level
958 Analytical Chemistry, Vol. 72, No. 5, March 1, 2000

Fig u re 4 . pH response of Al(salophen)-based membrane electrode
A) in the absence and (B) in the presence of 0.01 M salicylate.
(
Fig u re 3 . Calibration plots of electrodes B and K.
The standard deviation of the potential readings for electrodes B
The potentiometric responses of the sensor systems, incorpo-
rating Al(salophen) and Sn(salophen) membranes, were studied
-2
-3
and K in 1 × 10 and 1 × 10 M salicylate solutions over periods
of 20 min and 2 h were about 0.6 and 1.0 mV, respectively. The
detection systems are very stable and can be used over a period
of 1 month, without observing a considerable change in their
response characteristics. The slopes of the calibration graphs were
reproducible to within 1.2 mV/ decade over a period of 1 month.
The pH Response of the Electrodes. The potentiometric
response of both membrane electrodes was found to be sensitive
to pH changes. Figure 4A shows a typical pH response profile for
the Al(salophen)-doped membrane, evaluated by titrating 0.1 M
phosphoric acid solution with sodium hydroxide solution. Such a
-
7
-1
in the salicylate concentration range of 1 × 10 -1 × 10 M at
pH 7.0 and 25 °C. The calibration curves for these systems in the
linear region are shown in Figure 3. It can be seen that electrode
B, with 2.2% Al(salophen), shows a linear potentiometric response
-6
-1
over a wide concentration range of 1 × 10 -1 × 10 M salicylate,
with a Nernstian slope of -59.2 mV/ decade of concentration. For
electrode K, with Sn(salophen) ionophore, about the same linear
range with a slope of -57.2 mV/ decade was observed. The linear
range of the electrode response for these sensors is about five
decades of concentration, which is wider than those reported for
the highly selective salicylate electrodes.10,17,23,24
potentiometric pH response can be ascribed to the coordination
of water molecules as axial ligands to the central metals,19 i.e.,
The limits of detection, defined as the concentration of
salicylate obtained when extrapolating the linear region of the
calibration curve to the baseline potential, for different electrodes
are given in Table 1. As can be seen, electrodes B and K show
+ -
formation of [Al(salophen)(H
(
2
O)
2 2
] X and [Sn(salophen)(H O)-
-
+ -
X )] X complexes. Once associated, the water can readily lose
a proton to the solution, yielding hydroxide-coordinated metal
-
complexes of the following type: [Al(salophen)(H
[
2
O)(OH )] and
-
6
-7
detection limits of about 1 × 10 and 8 × 10 M, respectively.
The limit of detection obtained in this work is several orders of
magnitude below the recommended therapeutic level of salicylate
in biological fluids (e.g., whole blood, plasma, serum and urine,
-
-
Sn(salophen)(OH )X ]. This results in a response analogous to
that resulting from anion coordination at the same axial site. The
mechanism of pH response appears to be similar in nature to those
found with the membranes doped with manganese(III) and tin-
-
4
∼
1.5 × 10 M). Consequently, these samples can be substantially
IV) porphyrins and phthalocyanines.10,17,25,26 However, when those
(
diluted with a suitable buffer solution to minimize variation in
sample pH and probably decrease the effect of interferences. The
electrode also covers the range of both acute and chronic cases
of salicylate intoxication.
same salophen-based membranes are conditioned in 0.05 M
sodium salicylate solution, the response of the electrode is hardly
affected by the change in pH in the range of about 3-8.5 for both
membranes (Figure 4B). The behavior of the electrodes at high
pH can be explained in terms of the increased interference from
hydroxide ions. Protonation of salicylate anion may be the reason
for potential changes at low pH values. The working pH range
over which the electrodes can be used (3-8) covers the physi-
ological conditions (pH 7.2-7.6). The optimum working pH for
the most selective salicylate electrodes are 1-2 pH units below
For analytical applications, the response time of a sensor is
an important factor. The response time of the electrodes, tested
by measuring the time required to achieve a steady-state potential
(
within (1 mV), was within 20-30 s for solutions with salicylate
-6
-1
levels in the range 1 × 10 -1 × 10 M, depending on the stirring
efficiency. The stability and reproducibility of the electrodes were
also tested. The potentials remained almost constant for ∼10 min
10,16,17,23,24
the physiological conditions.
(
drift e1 mV), after which a very slow divergence was observed.
(
25) Chaniotakis, N. A.; Chasser, A. M.; Meyerhoff, M. E.; Groves, J. T. Anal.
Chem. 1 9 8 8 , 60, 185-188.
(
(
23) Liu, D.; Chen, W. C.; Shen, G. L.; Yu, R. Q. Analyst 1 9 9 6 , 121, 1495-1499.
24) Li, Z. Q.; Yuan, R.; Ying, M.; Song, Y. Q.; Shen, G. L.; Yu, R. Q. Talanta
(26) Ma, S. C.; Chaniotakis, N. A.; Meyerhoff, M. E. Anal. Chem. 1 9 8 8 , 60,
1
9 9 8 , 46, 943-950.
2293-2299.
Analytical Chemistry, Vol. 72, No. 5, March 1, 2000 959

Ta b le 2 . P o t e n t io m e t ric S e le c t ivit y Co e ffic ie n t s o f t h e
Al(s a lo p h e n ) a n d S n (s a lo p h e n ) Me m b ra n e Ele c t ro d e s a
Ta b le 3 . Re s u lt s o f t h e An a lys is o f P h a rm a c e u t ic a l
P re p a ra t io n s a n d a n Urin e S a m p le
log Ksal,x of different membranes
potentiometry
interfering ion, x
B
F
G
J
K
sample
label value
electrode B
electrode J
colorimetry
-
Aspirin Content (mg/ Tablet)a
N3
Br
-4.0
-4.0
-4.1
-4.3
-4.0
-4.3
-2.9
-3.8
-4.2
-5.3
-2.3
-5.7
-5.6
-2.0
-4.9
-4.0
-4.0
-5.1
-5.1
-5.6
-4.6
-4.8
1.0
-4.2
-3.9
-3.8
-4.4
-4.3
-4.5
-1.3
-2.9
-4.2
-5.4
-0.6
-5.5
-5.0
-0.5
-4.4
-3.6
-3.5
-4.2
-4.3
-4.9
-3.5
-4.0
1.0
-3.5
-3.5
-3.5
-3.8
-3.4
-4.0
-2.9
-3.8
-3.8
-4.4
-2.2
-5.1
-5.0
-1.7
-4.4
-3.5
-3.7
-4.5
-4.4
-5.0
-4.0
-4.3
1.3
-4.1
-4.2
-3.7
-4.2
-4.0
-4.2
-3.8
-4.1
-3.9
-4.6
-2.6
-5.3
-5.4
-2.2
-5.6
-3.9
-4.5
-5.3
-5.3
-5.8
-5.3
-5.2
1.5
-3.2
-3.1
-3.4
-3.7
-3.5
-4.0
-1.4
-3.2
-4.0
-4.1
-1.4
-5.0
-4.7
-1.0
-4.1
-3.2
-3.3
-4.1
-4.2
-4.6
-3.4
-4.0
0.8
-
1
2
3
100
325
500
100.4
311.4
468.0
98.1
309.6
459.0
94.1
296.6
446.4
-
HCO3
-
Cl
-
CN
Salicylate Content in Urine Sample (mg/ 100 mL)a
-
F
7.45
7.40
7.04
-
I
-
NO3
NO2
C2O4
ClO4
HPO4
SO4
SCN
maleate
acetate
benzoate
tartrate
adipate
citrate
a
Average of three determinations.
-
2
-
-
2
-
2
-
oxalate, phosphate, sulfate, maleate, tartrate, adipate, phthalate,
and nitrophthalate, have not been reported for the most selective
salicylate electrodes.10,16,17,23,24 The report on these anions by
Hassan and Hamada14 shows selectivity coefficients that are
generally higher than those of electrode J by ∼2 orders of
-
16
magnitude. The selectivity coefficients reported for bromide,
chloride,16,17,23 perchlorate,10,16,17,23 thiocyanate,10,17,24 and acetate16
are superior to the proposed electrodes, but for the other anions,
the selectivities observed in this report are comparable to or better
than those reported for the most selective salicylate electrodes.
The electrode based on Al(salophen) without additive (electrode
B) is generally more selective to salicylate, compared to that based
on the same electrode with 1% cationic additive (electrode F). In
the case of Sn(salophen) ionophore, although the selectivities in
the absence of the anionic additive are generally worse than those
of the Al(salophen) (electrode B), the presence of 1.3% of NaTPB
in the Sn(salophen) membrane results in better selectivities over
aluminum ionophore. The KSal,OH values, given in Table 3, were
obtained by the fixed interference method using the data shown
in Figures 1 and 2, which were in good agreement with those
obtained by the fixed parent ion using Figure 4. From the data
given in Figure 4B, it can be seen that the interference of
hydroxide ion becomes significant at pH values above 8.4, and
therefore, the interference from hydroxide is negligible at the
working pH of 7.0. Meyerhoff and co-workers10 also obtained the
selectivity coefficient for the salicylate relative to hydroxide ion,
from the calibration plot at pH 7.2. They reported a log KSal,OH
value of 4.2 at this pH, but the interference at pH 5.5 was
negligible.
phthalate
-nitrophthalate
hydroxide
3
b
a
All values obtained in 0.05 M phosphate buffer solution, pH 7.0,
b
at an anion concentration of 0.01 M. The selectivity for salicylate
relative to hydroxide were obtained at pH 8.4 using the fixed
interference method.
Selectivity. The most important characteristic of any ion-
sensitive sensor is its relative response for the primary ion over
other ions present in solution, which is expressed in terms of the
potentiometric selectivity coefficients. Potentiometric selectivity
coefficients (KSal,X), describing the preference by the membrane
-
for an interfering ion X relative to salicylate, were determined in
.01 M solutions of the corresponding sodium salts by the separate
0
solution method, except for hydroxide interference, which was
estimated by the fixed interference method.27 Concentrations were
used rather than activities due to uncertainties in estimating the
ionic strength of the background electrolyte. The potentiometric
ion selectivity coefficients of different electrodes, based on Al-
(
salophen) and Sn(salophen) membranes, are summarized in
Table 2. The selectivity coefficient patterns clearly indicate that
the electrodes are highly selective to salicylate over a number of
other anions. A typical selectivity pattern for a series of anions
presented by electrode B is as follows: salicylate . thiocyanate
perchlorate > iodide > nitrate > benzoate > acetate > bromide
cyanide - azide > carbonate > nitrite > chloride > fluoride >
phthalate > nitrophthalate > maleate > adipate > tartrate >
oxalate > sulfate > citrate > phosphate. Selectivities over the
organic and inorganic anions studied in this paper are better than
those of other salicylate sensors based on enzyme electrodes,28
Nitron,14 ion-exchanger membranes,10,17,29 and membranes based
on several metal complexes.11,13,15 The selectivities for salicylate
over several anions, including azide, carbonate, cyanide, fluoride,
Mechanism of Salicylate Response and Selectivity. There
have been several reports on the use of quaternary ammonium
salts for the development of salicylate-selective electrodes.10,11,30,31
Although these electrodes offer a fairly good discrimination of
hydrophilic anions, their preferred anions are perchlorate, thio-
cyanate, and iodide, respectively. The Al(salophen)- and Sn-
>
-
(
salophen)-doped membrane electrodes displayed substantially
improved selectivity for salicylate over several other anions. Most
of these anions would be expected to interfere seriously with
classical anion-exchanger-type membrane electrodes. The high
selectivity for salicylate over perchlorate, thiocyanate, and iodide
clearly deviates from the conventional Hofmeister anion response
pattern and suggests that salicylate is directly interacting with the
(
27) Guilbault, G. G.; Durst, R. A.; Frant, M. S.; Freiser, H.; Hansen, E. H.; Light,
T. S.; Pungor, E.; Rechnitz, G. A.; Rice, N. M.; Rohm, T. J.; Simon, W.;
Thomas, J. D. R. Pure Appl. Chem. 1 9 7 6 , 48, 127-132.
28) Fonong, T.; Rechnitz, C. A. Anal. Chim. Acta 1 9 8 4 , 158, 357-362.
29) Midgley, D. Anal. Chim. Acta 1 9 8 6 , 182, 91-101.
(30) Choi, K. K.; Fung, K. W. Anal. Chim. Acta 1 9 8 2 , 138, 385-391.
(31) Mitsana-Papazoglou, A.; Diamandis, E. P.; Hadjiioannou, T. P. Anal. Chim.
Acta 1 9 8 4 , 159, 393-399.
(
(
960 Analytical Chemistry, Vol. 72, No. 5, March 1, 2000

Ta b le 4 . Co m p o s it io n o f S im u la t e d S e ru m
Ta b le 5 . De t e rm in a t io n o f S a lic yla t e Ad d e d t o
S yn t h e t ic S e ru m S a m p le
compound
concn (mM)
compound
concn (mM)
electrode B
electrode J
D,L-alanine
L-arginine
L-aspartic acid
L-cysteine
glycine
0.41
0.21
0.88
0.071
0.14
0.14
0.20
D,L-methionine
L-phenylalanine
L-serine
D,L-tryptophan
NaHCO3
0.034
0.16
0.16
0.085
8.0
amt added
mmol/ L)
amt founda
(mmol/ L)
amt founda
(mmol/ L)
(
% recovery
% recovery
0
1
1
2
3
5
.990
.48
.96
.91
.65
.66
0.993
1.43
1.89
2.71
3.74
5.37
100.3
96.6
96.4
93.2
97.2
94.9
1.02
1.52
2.01
2.87
3.94
5.86
103.0
102.7
102.6
98.6
102.3
103.5
L-histidine
L-lysine
NaCl
citric acid
88.8
0.17
a
Average of three determinations.
metallosalophens as an axial ligand. The strength of this interac-
tion, relative to other anions, dictates the observed selectivity
pattern of the electrodes. The hard metal centers in both
ionophores endow a strong oxophilic character on the complexes
and interact strongly with the carboxylate group of salicylate,
which acts as a hard base.
and its beneficial effect on Sn(salophen) membranes, which
suggest that these compounds act as electrically neutral and
charged ionophores, respectively, and (2) the acid-base titration
curve (Figure 4A), which suggests the pH-dependent deprotona-
tion of the axial water molecules leaving hydroxide ions, the
following mechanisms may be proposed for the potentiometric
response of these membranes toward salicylate:
As can be seen in Table 2, the membranes containing TOMACl
(
electrodes F and K) generally show less selectivity to salicylate
in comparison to the electrodes without the cationic additive
(
electrodes B and G). Such a difference is more pronounced for
-
-
-
4
the highly lipophilic ClO , SCN , and I anions. The anion
responses observed for the electrodes containing TOMACl may
stem from the ion-exchange process that occurs to some extent
at the membrane surface.
H O
2
-H+
+ -
-
0
[
Al(salophen)X ] y z [Al(salophen)(H O) ] X y
z
2
2
+
sal-
z
-
0
[
Al(salophen)(H O)(OH )] y
2
Recently, there have been several reports on the effect of
anionic additives on the potentiometric selectivity of the membrane
electrodes.9,17,32 These reports demonstrated that for ionophores
that operate via a charged carrier mechanism, incorporation of a
certain ratio of fixed anionic sites into the membranes improves
the selectivity of electrodes. The effect of NaTPB on the selectivity
of Al(salophen)- and Sn(salophen)-doped membranes was studied.
Addition of NaTPB to the Al(salophen)-based membrane wors-
ened the performance of the electrode, so that the electrode was
no longer selective to salicylate (electrode E). However, the
selectivity of the Sn(salophen)-based electrode was considerably
improved in the presence of the anionic additive (electrode J).
As can be seen from the selectivity coefficients given in Table 2,
electrode J with 1.3 wt % NaTPB (∼39 mol % relative to the
ionophore) shows the highest selectivity among the different
compositions studied for both ionophores. It is interesting to note
that, although the Al(salophen) membrane (electrode B) generally
shows somewhat better selectivities over the corresponding
electrode based on Sn(salophen), the reverse is true in the
presence of the anionic additive. According to the theoretical
models that predict the effect of lipophilic anionic additives on
the selectivity of the membrane electrodes,9,32 the above studies
involving these effects suggest that Al(salophen) ionophore acts
on the basis of a neutral carrier mechanism but Sn(salophen)
ionophore behaves as a charged carrier in the membranes.
Previous studies have shown that aluminum salen19 and tin
neutral ionophore
-
-
-
+
[
Al(salophen)(sal )(OH )] M
H O
2
-
0
[Sn(salophen)(X ) ] y
z
2
-H+
+ -
-
[
Sn(salophen)(H O)X ] X y
z
2
charged ionophore
-
- 0
[
Sn(salophen)(OH )X ]
+
+ -
sal-
z
-
[Sn(salophen)(H O)X ] X y
2
charged ionophore
-
- 0
[
Sn(salophen)(sal )X ]
Analytical Applications. With the wide use of aspirin, there
is an increasing need for measurement of “free” salicylate in
biological samples such as urine and serum. The high degree of
salicylate selectivity exhibited by these metallosalophens makes
them potentially useful for monitoring concentration levels of
“free” salicylate in biological samples. For therapeutic drug
monitoring, determining the free concentration of a drug is
claimed to be physiologically more relevant than determining its
total concentration.10 In this regard, experiments were performed
to determine the feasibility of using these electrodes to measure
salicylate in human urine samples. The urine sample was diluted
1:10 with phosphate buffer, pH 7.0. The calibration plot, obtained
under the same experimental conditions, was employed to evaluate
the concentration of salicylate in urine sample. The results
obtained by the potentiometric method are in good agreement
with those of the spectrophotometric procedure,33 as shown in
Table 3.
porphyrin26 exist as [Al(L)(H
]+ and [Sn(L)(H
-
+
2
O)
2
2
O)(X )] spe-
cies in aqueous solutions and that H
2
O groups occupy the axial
position of an octahedral coordination environment around the
central metals. On the basis of these reports, and the results of
this study, i.e., (1) deteriorating effect of NaTPB on Al(salophen)
(
32) Schaller, U.; Bakker, E.; Spichiger, U. E.; Pretsch, E. Anal. Chem. 1 9 9 4 ,
6, 391-398.
6
(33) Trinder, P. Biochem. J. 1 9 5 4 , 57, 301-303.
Analytical Chemistry, Vol. 72, No. 5, March 1, 2000 961

Experiments were conducted to measure the concentration of
salicylate added to a synthetic serum sample, the composition of
which is listed in Table 4. The concentration of each component
was chosen to match its normal level in human serum.34 The
results of salicylate determination, summarized in Table 5, show
an average recovery of 96.4% for electrode B and 102.1% for
electrode J, indicating that the constituents of the synthetic serum
sample do not significantly interfere with the detection of salicy-
late. These electrodes seemed to provide an alternative device
for the direct determination of salicylate in biological samples.
The proposed electrodes were used for the determination of
salicylate content of the hydrolyzed pharmaceutical preparations.
Tablets of different samples of aspirin were treated according to
the procedure described above, and the resulting solutions were
used for the determination of salicylate content by potentiometric
and spectrophotometric methods. The results obtained by the
electrode method (Table 3) are in good agreement with those
obtained by the spectrophotometric method.35
CONCLUSIONS
The results of this study show that the potentiometric method
based on Al(salophen) and Sn(salophen) membranes coated on
graphite electrodes may provide an attractive alternative for the
determination of salicylate. The proposed sensors are very easy
to prepare and show high sensitivity and wide dynamic range.
High selectivity, very low detection limit, and rapid response make
these electrodes suitable for measuring the concentration of
salicylate in a wide variety of samples, including pharmaceutical
preparations and biological samples, without the need for pre-
concentration or pretreatment steps and without significant
interaction from other anionic species present in the samples.
ACKNOWLEDGMENT
The authors express their appreciation to the University of
Isfahan Graduate Office for financial support of this work.
Received for review July 8, 1999. Accepted November 19,
1
999.
(
(
34) Pau, C. P.; Rechnitz, G. A. Anal. Chim. Acta 1 9 8 4 , 160, 141-147.
35) British Pharmacopoeia; University Press: Cambridge, 1993; Vol. II.
AC990749W
962 Analytical Chemistry, Vol. 72, No. 5, March 1, 2000