ОРИГИНАЛЬНЫЕ СТАТЬИ =
УДК 543
POLY(ANILINE) SOLID CONTACT ION SELECTIVE ELECTRODE FOR UDENAFIL
© 2010 Won-Sik Han*, Jang-Ki Kim*, Koo-Chun Chung**, Joo-Yeon Hong***, Jong-Ki Hong***, Jeong-Hoon Kim****, Tae-Kee Hong*
*Department of Chemistry, Hanseo University
Seosan, Chungnam, 356-820, Korea **Department of Chemistry, Konkuk University
Seoul, 143-701, Korea ***College of Pharmacy, Kyunghee University Seoul, 130-701, Korea ****Research Laboratory, Dong-A Pharmaceutical Company Limited Yongin, kyunggi-Do, 446-905, Korea Received 01.07.2009; in final form 16.03.2010
Udenafil is an oral agent for treating male erectile dysfunction. The poly(aniline) solid contact selective electrodes for udenafil have been fabricated from PVC cocktail solutions with three ion selective ion pairs. This solid contact electrode contains three layers of Pt/electro-conductive poly(aniline) polymer/PVC film with an ionophore with a thickness of 2.5 ± 0.1 mm. We compared the slopes of EMF responses and the response range of a solid contact electrode based on Udenafil-TmClPB ion pair with those based on Udenafil-PMA and Udenafil-TPB ion pairs and showed that the response slopes were influenced by plasticizers. The EMF response slopes of Udenafil-TmClPB-based solid contact electrodes equalled 58.0 mV/decade (at 20 ± 0.2°C) and their linear response dynamic ranges were 1.0 x 10-2~1.0 x 10-585 M (r2 = 0.9984). When electrodes with 6 different plasticizers based on Udenafil-TmClPB were compared, as the dielectric constant of PVC plasticizer increased, so was the response slope at the same time. Having applied the electrodes to artificial serum directly, we could get same satisfactory results [Nernstian slope : 60.3 mV/decade, dynamic range : 1.0 x 10-2~1.0 x 10-5 78 M (r2 = 0.9978) in artificial serum]. Solid contact electrodes with Udenafil-TmClPB have shown the best selectivity, reproducibility of EMI; long-term stability, and short response time (<20 s).
Key words: Solid Contact Electrodes, Udenafil, Poly(aniline).
Phosphodiesterase type 5 (PDE5) inhibitors are vasoactive drugs that have been developed for the treatment of erectile dysfunction [1]. PDE5 inhibitors act by blocking the degradation of cGMP, which is increased in the vascular smooth muscle cells in the endothelium by l — argi-nine in the presence of NO synthase, leading to relaxation of the vessels [2]. It was reported that zaprinast enhances the endothelium-dependent, NO — mediated vasodilation in an intact lamb with experimental pulmonary hypertension [3]. Halcox et al. reported that sildenafil citrate, which was the first PDE — 5 inhibitor approved for treating erectile dysfunction, dilated the epi-cardial coronary arteries, improved the endothelial dysfunction, and improved the physiologic coronary vaso-motion in patients with coronary artery disease (CAD) [4, 5]. Udenafil (5-[2-propyloxy-5-(1-methyl-2-pyrol-lidinylethylamidosulphonyl)phenyl]-1-methyl-3-pro-pyl-1,6-dihydro-7-H-pyrazolo (4,3-d) pyrimidin-7-one) is also a potent and selective PDE5 inhibitor developed by the Dong-A Pharmaceutical Company in Korea as an oral agent for treating male erectile dysfunction. (Fig. 1) For these drugs, few reports appeared describing
accurate spectrochemical, chromatographic and elec-troanalytical techniques for their quantification [6, 7]. However, most of these methods are expensive, suffer from lack of selectivity and require careful control of conditions and considerable time for routine analysis [8, 9]. Therefore, precise and simple methods for the quantification of udenafil in pharmaceutical preparations are required. Recent years have seen an upsurge of interest in the application of ion sensors in the field of medicinal analysis. These instruments provide fast, accurate, reproducible and selective determination of various species [10, 11]. Solid contact electrodes have especially great advantages of mechanical flexibility, possibilities of miniaturization and microfabrication. The solid membranes are easy to construct and better suited for multi-ion sensors because they can be miniaturized and are not restricted to one side of the electrode. Therefore, these are gaining popularity in medical, biotechnological, pharmaceutical and environmental fields [12]. The solid contact electrodes exhibit good performance, such as better stabilization of the base potential, reproducibility, selectivity, wide response range, and fast response time. We
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2 3 4 5 6 7 —log (concentration of Udenfil)
Fig. 1. Formula of udenafil and response characteristics of udenafil solid contact electrodes with various plasticizer in pH 4.5 acetate-buffered udenafil solution. -¡- ; (Udenafil-TmClPB) ion pair 0.050 : PVC 0.19 : NPOE 0.35 : KTp-ClPB 0.001, ; (Udenafil-PMA) ion pair 0.010 : PVC 0.19 : NPOE 0.35 : KTpClPB 0.001 ; -A- (Udenafil-TPB) ion pair 0.010 : PVC 0.19 : DOP 0.45 : KTpClPB 0.001
have recently developed and reported such solid contact electrodes for hydrogen ion and many other ions based on conducting polymers of poly(aniline) and poly(pyr-role) in PVC with various carriers [13, 14]. In the last paper, we described the application of two developed ion selective solid contact electrodes for udenafil determination in pharmaceutical preparations using the ion-association complex of udenafil with the electroactive phase containing sodium tetraphenylborate (TPB) or phosphomolybdic acid (PMA) in a poly vinyl chloride (PVC) matrix over a wide concentration range. The slopes of EMF responses showed, respectively, 55.0, 47.0 mV/decade, and the linear response dynamic ranges were 1 x 10-2~1 x 10-573 M for PMA based solid contact electrodes and 1 x 10-2~1 x 10-504 M for udenafil-TPB based solid contact electrodes [15]. The proposed methods are successfully applied for the determination of udenafil in the presence of other components.
In this work, we describe the poly(aniline) solid contact electrode with Udenafil-TmClPB ionophore dissolved in o-nitrotoluene for udenafil ion detecting. Vinous plasticizers (DOS, NPOE, DOP, TEHP, DOA, DBP) were tested for best response. General physical properties of these electrodes such as responsibility, effect of interfering ions, response time, and stabilization time and the application of these properties to the analysis of an artificial serum were studied.
EXPERIMENTAL
Reagents. Aniline and tetrahydrofuran (THF) were purified by vacuum distillation. For all experiments, analytical grade chemicals and doubly distilled and deminer-alized water were used. The membrane matrix high molecular weight poly(vinylchloride) (PVC, n = 1,100), the
anionic additive potassium tetrakis(4-chlorophenyl) borate (KTpClPB), the plasticizers 2-nitrophenyl-octylether (o-NPOE), tris(ethylhexyl)phosphate (TEHP), bis(2-ethylhexyl)adipate (DOA), dioctylphthalate (DOP), and bis(2-ethylhexyl)sebacate (DOS), the solvent THF, sodium tetraphenylborate (TPB), phosphomolybdic acid (PMA), and aniline were from Aldich Co.
Polymerization [16]. Electrochemical experiments were performed in a conventional cell with three electrodes. A saturated calomel electrode was used as the reference electrode and all potentials were recorded and reported with respect to this electrode. Platinum wires (1 mm in diameter, 50 mm in length) were used as the working and counter electrodes. Electro-polymerization was carried out at the one end of a platinum wire by cyclic voltammetry in 3.0 x 10-2 M aniline and 6.0 x 10-2 M HCl solution. Cyclic voltammograms were recorded using a potentiostat (EG & G 273A). For electrochemical polymerization of aniline, the potential was swept between 0.0 V and 1.0 V at scan rate of 100 mV/s. The potential cycling was repeated up to 30 cycles and stopped at 1.0 V After electrodeposition, the poly(aniline) was washed with distilled water and then dried for 24 h in an 80°C oven. Then the part of the Pt in Pt-poly(aniline) electrode was covered with a thermo-contractive insulation tube.
Preparation of cocktail solutions and fabrication of solid contact electrode. Typical cocktail solution consists of ion-pair 0.010 ~ 0.100 : PVC 0.30~0.40 : plasticizer 0.50~0.70 : KTpClPB 0.001~0.010. All components were dissolved in THF. The solid contact electrodes were produced by dipping the Pt-poly(aniline) electrode directly into the cocktail solution to coat it with a thin film. The resulting solid contact electrode contains three layers of Pt/electroconductive polymer/PVC film with an iono-phore with a thickness of 2.5 ± 0.1 mm.
EMF measurements. The emf values were measured at 20 ± 0.2°C using a model 355 Ion-analyzer (Mettler-Toledo Ltd., England). In all experiments, the pH measurements of the sample solutions were determined with a Mettler-Toledo InLab 412 glass electrode. The external reference electrode was a double-junction calomel electrode Orion 90-20-00 (Orion Research, U.S.A.). The standard deviation arising from this equipment was <0.1 mV for a single determination. Before use, the electrodes were conditioned in distilled water for at least 2 h.
Measurements of stabilisation time and respons time. [17]. Time required for stabilization of the electrode was measured in 1.0 x 10-3 M pH 4.5 acetate buffer udenafil solution with an ion analyzer (Orion Model 720A). The dry electrode was placed in udena-fil-acetate buffer solution to attain a stable potential for 4 hours. Then 10.00 mL of 1.0 x 10-2 M udenafil-pH 4.5 acetate buffer solution was added while the solution was vigorously stirred magnetically to measure the potential change and time required for the stabilization of the potential in terms of time required/unit
CH
concentration change. Electrode response was considered stable when AE/At became less than 0.1 mV/min .
Udenafil standard sample solution. A stock solution (1.0 x 10-2 M) of udenafil at pH 4.5 was prepared by dissolving 0.5167 g of udenafil in 100 mL of water adjusted with acetate bu
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