ОРИГИНАЛЬНЫЕ СТАТЬИ =
УДК 543
A NEW SENSOR FOR ELECTROCHEMICAL DETERMINATION OF CAPTOPRIL USING CHLORPROMAZINE AS A MEDIATOR AT A GLASSY CARBON ELECTRODE © 2012 г. Ali A. Ensafi, A. Arabzadeh
Department of Chemistry, Isfahan University of Technology Isfahan 84156-83111, Iran Received 09.12.2009; in final form 05.05.2011
A new simple, selective and rapid cyclic voltammetric method is reported for the accurate and precise determination of captopril using chlorpromazine as a suitable electrocatalyst. It has been shown by cyclic voltam-metry, single step chronoamperometry and electrochemical impedance spectroscopy that chlorpromazine can catalyze the oxidation of captopril in aqueous buffer solution and produces a sharp oxidation peak current at about 0.625 V vs. saturated calomel reference electrode. The catalytic oxidation peak current of captopril is linearly dependent on its concentration and enables the determination of captopril over the concentration range of 8—1000 цМ at pH 5.0, with a detection limit of 4.8 цМ. The relative standard deviation for the determination of 400 цМ captopril is 0.66% (n = 9). The influence of potential interfering substances on the determination of captopril was studied. The method was satisfactorily applied to the determination of capto-pril in real samples such as drug and urine.
Keywords: electrocatalytic, captopril, cyclic voltammetric, tlectrochemical impedance spectroscopy, chro-noamperometry.
The angiotensin-converting enzyme inhibitor, captopril (1 - [ 3 -mercapto - 2- (S) -methyl-1 - oxopropyl] -(S)-proline), scheme 1, has been used in the treatment of essential hypertension [1] and to reduce mortality in patients with acute myocardial infraction [2]. Captopril, as a chelating agent, has been proposed to complex cysteine in the treatment of cystinuria, an autosomal recessive genetic defect of the transepithelial transport of cystine and other dibasic amino acids in the kidney [3—5]. Some studies indicate that captopril acts as an antioxidant both by scavenging reactive oxygen species (ROS) and by increasing the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase [6].
O
CH3 J^y
HOOC
Scheme 1. Structure of captopril (CPL).
Unfortunately, administering CPL for therapeutic purposes leads to undesirable side effects. Preliminary research has indicated significant loss of zinc in urine due to the intake of CPL [7]. Although details remain unclear, it now appears that chronic use of CPL may lead to a zinc deficiency [8]. CPL is metabolized in the liver (it is oxidized into the corresponding disulfide) and is excreted mainly with the urine with 40—60% of
the drug excreted unchanged [9]. An uncommon yet potentially serious side effect of CPL treatment (in common with other angiotensin-converting enzyme inhibitors) is increased blood potassium levels [10—12]. Therefore, the determination of CPL is important from a physiological point ofview as well as for the purposes of quality control.
Several methods have already been reported for the determination of captopril in pharmaceutical formulations and biological fluids, including liquid chromatography with electrochemical [13, 14] and with fluorescence [15] detection, capillary zone electrophoresis with UV detection [16] and with laser-induced fluorescence [17], spectrophotometry with visible [18] and ultraviolet [19—22] detection, fluorometry [23], flow-injection with chemiluminescence detection [24], and mass spectrometry [25], The cathodic stripping volta-mmetry using Hg-electrode [26] and square wave vol-tammetry using Hg-electrode [27] have been used for captopril determination.
Amperometric and voltammetric detections are inexpensive and sensitive techniques therefore, they have been widely used to detect electro-active compounds in pharmaceutical formulations, biological matrices, and medicinal herbs. Voltammetric detection is also an extremely promising means for the determination of electroactive impurities in pharmaceutical formulations. Since captopril contains —SH group, it is electroactive, making it suitable for electrochemical detec-
Fig. 1. Cyclic voltammetric behavior of 1.0 mM chlorpro-mazine at glassy carbon electrode in universal buffer (pH 5.0) with scan rate of 50 mV s-1.
tion using Hg-electrode. However, this electrode is toxic and environmentally is not safe to use.
Based of our knowledge, there is one reported paper about the voltammetric determination of captopril using ferrocenedicarboxylic acid as a mediator [28]. However, the influences of some urine components such as uric acid, L-cystein, glutathione and kreatinin were not studied. In this work, we proposed chlorpro-mazine as a suitable mediator for the rapid and highly selective voltammetric determination of CPL on the surface of a glassy carbon electrode. As far as we know, electrocatalytic determination of any drug using modified electrode with chlorpromazine as a mediator has not been reported in literature. In this study, cyclic vol-tammetry (CV), single potential step chronoamperom-etry and electrochemical impedance spectroscopy (EIS) were used to establish the electrocatalytic behavior of chlorpromazine.
EXPERIMENTAL
Reagents. All chemicals were of analytical reagent grade and used without any purification, unless stated otherwise, and all the solutions were made up by doubly deionized water.
Captopril solution, 1.0 x 10-2 M, was prepared daily by dissolving 0.0217 g captopril in water and diluting the solution to 10 mL with water in a 10-mL volumetric flask. The solution was kept in a refrigerator at 4°C and in dark. More dilute solutions were prepared by serial dilution with water.
A 1.0 x 10-2 M chlorpromazine solution was prepared daily by dissolving 0.089 g chlorpromazine in wa-
ter and diluting the solution to 25 mL with water in a 25-mL volumetric flask.
Universal buffer solutions (boric acid, phosphoric acid, acetic acid (0.04 M) and sodium hydroxide, 0.2 M) with different pH values were used for the study of the influence of pH.
Captopril tablets (Exir Pharmaceutical Co., Iran, labeled 25 mg captopril per tablet) were purchased from Red Cross drug store in Isfahan.
Apparatus. Electrochemical measurements were done with Micro-Autolab, ptentiostat/galvanostat instrument, connected to a three-electrode cell, MicroAutolab ^3AUT70751 linked with a computer (Pentium IV, 1200 MHz) and cell linked with micro-Autolab software. A conventional three-electrode cell was used for all experiments. Glassy carbon electrode was used as a working electrode, platinum wire was used as an auxiliary electrode, and an SCE electrode was used as reference electrode. All potentials were measured versus the SCE.
Electrochemical measurements were carried out in a conventional three-electrode cell, powered by an electrochemical system comprising the Autolab (AUT83593). For impedance measurements, a frequency range of10 kHz to 1 Hz was employed. The AC voltage amplitude used was 5 mV.
A pH-meter (Corning, Model 140) with a double junction glass electrode was used to check the pH of the solutions.
Preparation of real samples.Ten tablets of captopril labeled with amount of 25 mg per tablet were completely ground and homogenized. 100 mg of the powder was accurately weighted and dissolved with ultra-sonication in 10 mL of buffer solution (pH 10.0). Then, 0.10 and 0.15 mL volumes of the solution were diluted to 10 mL using 0.04 M buffers and the captopril contents were measured using the recommended procedure.
Urine samples, used for measurements, were cen-trifuged and diluted 100-times with the buffer solution. The standard addition method was used for the determination of captopril in real samples.
RESULTS AND DISCUSSION
Electrochemistry of the mediator. Electrochemical determination of CPL is difficult using an ordinary GCE due to large oxidation overpotential. One promising approach for minimizing overpotential of analytes is the use of electrocatalysis. We used chlorpromazine as a mediator. Fig. 1 shows cyclic voltammetric behavior of chlorpromazine at a glassy carbon electrode in the universal buffer (pH 5.0). The electrochemical behavior of chlorpromazine in this condition yielded an oxidation/reduction process (Fig. 1, a in curve A or B). In addition, the cyclic voltammograms of chlorprom-azine at the surface of GCE in a buffer solution (pH 5.0) in the absence and presence of 1000 ^M cap-
Fig. 2. Cyclic voltammogram of a solution on a glassy carbon electrode at a scan rate of 50 mV s-1 and at pH 5.0:
(a) buffer solution (in 0.1 M KCl) in the absence of CPL;
(b) buffer solution (in 0.1 M KCl) in the presence of 1000 цМ CPL; (c) as (a) in the presence of1000 цМ chlorpromazine; (d) as (c) in the presence of 1000 цМ CPL.
topril are presented in Fig. 2. Captopril did not show any distinguishable anodic peak in the scanning region potential of 0.00 to + 1.10 V vs. SCE. As the results show, in the absence of captopril, a pair of well-defined redox peaks of chlorpromazine can be observed
545
(Fig. 1, A). Upon addition of 1000 цМ captopril, a drastic enhancement was observed in the anodic peak current close to the formal potential of chlorprom-azine(Red)/chlorpromazine(Ox) redox couple, while no cathodic current was observed in the reverse scan of potential. This behaviour is consistent with a very strong electrocatalytic effect. The process corresponds to an EC' catalytic mechanism (Diagram 1), where electro-chemically formed chlorpromazine(Ox) reacts chemically with CPL diffused toward the electrode surface, while the simultaneous oxidation of regenerated chlor-promazine(Red) causes an increase in the anodic current. For the same reason, the cathodic current of the modified electrode is not observed in the presence of 1000 цМ CPL (Fig. 2). The plot of the anodic peak current was linearly dependent on v1/2 with a correlation coefficient of 0.9992 at all scan rates (Fig. 3, insert (B)). This behavi
Для дальнейшего прочтения статьи необходимо приобрести полный текст. Статьи высылаются в формате PDF на указанную при оплате почту. Время доставки составляет менее 10 минут. Стоимость одной статьи — 150 рублей.