ЖУРНАЛ АНАЛИТИЧЕСКОЙ ХИМИИ, 2013, том 68, № 2, с. 197-202
ОРИГИНАЛЬНЫЕ СТАТЬИ
УДК 543
DETERMINATION OF FLUOXETINE IN PHARMACEUTICAL PREPARATIONS AND BIOLOGICAL SAMPLES USING POTENTIOMETRIC SENSORS BASED ON POLYMERIC MEMBRANES © 2013 M. Arvand*, N. Ahmadi Rad**
*Department of Chemistry, Faculty of Science, University of Guilan P.O. Box 1914 Rasht, Iran **Environmental Research Institute, University of Applied Science and Technology P.O. Box 41635-3114Rasht, Iran Received 05.10.2010; in final form 07.07.2011
The construction and general performance of four novel potentiometric membrane sensors for the determination of fluoxetine have been described. The sensors are based on the formation of the ion association complex of fluoxetine with sodium tetraphenylborate and phosphotungstic acid as electroactive materialles, dispersed in a PVC matrix with dibuthyl sebacate (or diethyl sebacate) as a plasticizer. These sensors exhibit fast, stable and near-Nernstian response for the monocharged fluoxetine cation over wide concentration range from 3.0 x 10-6 to 1.2 x 10-2 M and pH 4.0—7.5. No interferences are caused by many inorganic and organic species. Direct potentiometric determinations of 5—100 p.g/mL of fluoxetine in drug and urine samples show good recovery of fluoxetine. The developed membrane electrodes have been used as an end point indicator electrode; the potentiometric titration of fluoxetine with sodium tetraphenylborate as a titrant has been monitored.
Keywords: fluoxetine, PVC-membrane electrode, ion-association complex, potentiometry.
DOI: 10.7868/S0044450213020023
The work which eventually led to the discovery of fluoxetine began at Eli Lilly in 1970 as collaboration between Bryan Molloy and Robert Rathbun. It was known at that time that antihistamine diphenhydramine showed some antidepressant-like properties. 3-Phenoxy-3-phenylpropylamine, a compound structurally similar to diphenhydramine, was taken as a starting point, and Molloy synthesized dozens of its derivatives. Testing the physiological effects of these compounds in mice resulted in nisoxetine, a selective norepinephrine reuptake inhibitor currently widely used in biochemical experiments [1, 2]. Later, hoping to find a derivative inhibiting only serotonin reuptake, another Eli Lilly scientist, David Wong, proposed to re-test the series for the in-vitro reuptake of serotonin, norepinephrine and dopamine. This test carried out by Jong-Sir Horng in May 1972 [2] showed the compound later named fluoxetine to be the most potent and selective inhibitor of serotonin reuptake of the series [3].
Fluoxetine (F) ((R,S)-N-methyl-3-(4-trifluoro-methylphenoxy)propan-1-amine), a selective serotonin uptake inhibitor, is one of the most frequently prescribed antidepressant (Fig. 1). One of the risks involved with F is the high suicide attempt rate of the population group to whom it is prescribed. Several in-
toxications by accidental overdoses or in suicide attempts of psychotic patients to whom F is often prescribed have been reported in the current literature for amounts ranging from 120 to 3000 mg, most of which have occurred in combination with other drugs [4].
Reported methods for the determination of fluox-etine are mainly based on high performance liquid chromatography [5—11] and gas chromatography [12—14]. Spectrofluoremetric methods have been also used by few researchers [15—17]. The reported spec-trophotometric methods for fluoxetine are based on charge transfer complexes with chloranil, 2,3-dichlo-
F3C
CH3 I 3
NH
HCl
Fig. 1. Fluoxetine hydrochloride structure.
ro-5,6-dicyanoquinone [18], ion pair complexes with methyl orange and thymol blue [19], pyrocatechol violet [20], bromothymol blue, bromocresol green and bromophenol blue [21], ion association compounds with erichrome cyanine R and chrome azurol S [22, 23] and colored vinylamino substituted quinones with haloquinones in the presence of acetaldehyde [24]. Most of these spectrophotometric methods are based on liqui—liquid extraction before measurement of absorption. The flow injection methods have also been reported for the determination of flouxetine using square wave adsorptive voltammetric method [25] and spectrophotometric method based on competitive complexation reaction with phenolphthalein-p-cyclo-dextrin inclusion complex [26]. Some of these methods, however, suffer from severe interferences from various organic compounds are not applicable to determining low drug concentrations and require sophisticated instruments. Ion selective electrodes (ISEs) are electrochemical transducers that respond selectively, directly and continuously to the activity of the free ion of interest in solution [27, 28]. Due to their advantages (sufficient selectivity and sensitivity, wide analytical range of the analyte concentration, low cost, fast response, simplicity of assembly, capability of measuring in colored and cloudy solution) they have found many applications, including studies of drugs with macromol-ecules [29-36].
In this work, we describe four potentiometric PVC-membrane sensors for the determination of fluoxetine in pharmaceutical preparations and in biological matrices. The membrane used in these electrodes was made from liquid-plasticized PVC and was based on water-insoluble ion pairs such as fluoxetine-tetraphe-nylborate (F-TPB) and fluoxetine-phosphotungstate (F-PT) as an ion-exchanger.
EXPERIMENTAL
Reagent grade o-nitrophenyl octyl ether (o-NPOE), dibutyl phthalate (DBP), dimethyl sebacate (DMS), diethyl sebacate (DES), dibutyl sebacate (DBS), dio-cthyl sebacate (DOS), tetrahydrofuran (THF), sodium tetraphenylborate (Na TPB), phosphotungstic acid (PTA) and high relative molecular weight PVC (all from Merck) were used as received. Fluoxetine hydrochloride (from Merck) was of the highest purity available and used without any further purification except for vacuum drying over P2O5. Triply distilled deionized water was used throughout. The pH adjustments were made with dilute nitric acid or potassium hydroxide solution as required.
Preparation of ion-pairs and electrodes. Preparation of fluoxetine-tetraphenylborate (F-TPB). About 20 mL of 0.01 M solution of F were mixed with 25 mL of 0.01 M solution of tetraphenylborate under stirring. The resulting precipitate was filtered off, washed with water and dried at 60°C.
Preparation of fluoxetine-phosphotungstate (F-PT). The preparation of fluoxetine-phosphotungstate was carried out by mixing the two solutions at the ratio of volumes 65 : 20, i.e., 65 mL of 0.01 M solution of F were mixed with 20 mL of 0.01 M solution of PT. The other procedures are similar to the one stated above.
For F-TPB electrode (electrode A), a mixture of PVC cocktail was prepared by dissolving 48 mg of PVC, 2.5 mg of F-TPB, 49.5 mg of DBS in 4 mL of THF. The cocktails and sensing membranes for other electrodes (B, C, and D) were prepared analogously, the compositions of the sensing membrane prepared were 48 mg of PVC, 2.5 mg of F-TPB, 49.5 mg of DES for the B electrode, 48 mg of PVC, 3 mg of F-PT, 49 mg of DES for the C electrode and 48 mg of PVC, 3 mg of F-PT, 49 mg of DBS for the D electrode, respectively.
The resulting clear mixture was transferred into 2 cm diameter glass dish. The solvent was evaporated slowly until an oily concentrated mixture was obtained. A Pyrex tube (3 mm i.d. on top) was dipped into the mixture for about 10 s so that a nontransparent membrane of about 0.3 mm thickness was formed. The tube was then pulled up from the mixture and kept at room temperature for about 1 h. The tube was then filled with an internal filling solution (1.0 x 10-4 M fluoxetine for A and B electrodes and 1.0 x 10-3 M fluoxetine for C and D electrodes). The electrodes were finally conditioned for 24 h by soaking in an external solution with the same internal solution concentration.
emf measurements. The emf measurements with the polymeric membrane electrodes were carried out with the following cell assemble:
Ag-AgCl/KCl (3 M)|internal solution|PVC mem-branejtest solution|Ag-AgCl, KCl (saturated).
All potentiometric measurements were made at 25 ± 1°C with a Metrohm (model 645) potentiometer. pH was measured by using of a Behine (model 2000) pH meter.
The emf observation was made relative to a double-junction saturated silver/silver chloride reference electrode (Philips) with the chamber filled with a potassium nitrate solution. A silver/silver chloride electrode (Metrohm) containing 3 M solution of KCl was used as the internal reference electrode. The performance of each electrode was investigated by measuring its potential in fluoxetine hydrochloride in the range of 1.0 x 10-7—2.0 x 10-2 M. Activities were calculated according to the Debye-Huckel procedure [37, 38].
RESULTS AND DISCUSSION
In this study, six plasticizers, DBP, DBS, DOS, DMS, o-NPOE and DES were used to examine the optimization of the membrane. The results obtained showed that the response performances of the prepared electrodes were rather different depending on the type of plasticizer, the proportion of the plasticizer to-
Table 1. Influence of the membrane composition on the potentiometric response characteristics (with F-TPB ion-pair)
No. Composition (wt %) Slope, mV/decade Linear range, M
PVC Plasticizer F-TPB
1 48.0 DBP 49.5 2.5 46.3 5.0 x 10-6- .3 x 10- -3
2 A 48.0 DBS 49.5 2.5 51.0 3.0 x 10-6- .3 x 10- -3
3 48.0 DOS 49.5 2.5 49.5 3.0 x 10-6- .3 x 10" -3
4 48.0 DMS 49.5 2.5 49.3 3.0 x 10-6- .3 x 10" -3
5 48.0 o-NPOE 49.5 2.5 48.8 3.0 x 10-6- .3 x 10" -3
6 B 48.0 DES 49.5 2.5 51.8 5.0 x 10-6- .3 x 10" 3
7 32.0 DES 65.5 2.5 48.6 1.5 x 10-6- .3 x 10" 3
8 65.5 DES 32.0 2.5 50.8 7.5 x 10-6- .3 x 10" 3
9 48.0 DES 50.0 2.0 43.4 5.0 x 10-6- .3 x 10" 3
10 48.0 DES 49.0 3.0 43.6 5.0 x 10-6- .3 x 10" 3
11 48.0 DES 48.5 3.5 42.1 5.0 x 10-6- .3 x 10" 3
Table 2. Influence of the membrane composition on the potentiometric response characteristics (with F-
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