Differential pulse voltammetry (DPV) and chronoamperometry (CA) were used to detect and determine acetylsalicylic acid (ASA) at a mildly oxidized boron-doped diamond (BDD) electrode in a neutral sodium sulphate solution as supporting electrolyte. ASA determination in unbuffered medium was achieved using neutralized standard and real samples. Over the concentration range of 0.01 mM–0.1 mM, linear calibration plots of anodic current peaks in DPV and anodic currents in CA experiments versus concentration were obtained with very high correlation coefficients and good sensitivity values. The limits of detection were situated around 1
Acetylsalicylic acid (ASA) or aspirin, the world’s oldest and best known nonsteroidal anti-inflammatory drug, continues to receive special attention due to its clinical effects on inflammation, fever, renal function, and platelet aggregation [
A survey in the literature indicates a variety of analytical techniques used for the detection and determination of acetylsalicylic acid. Generally, ASA is indirectly determined after the conversion to salicylic acid, its main hydrolysis product [
Acting as electroactive substance through salicylic acid, aspirin’s main hydrolysis product, ASA has also been electrochemically studied from a mechanistic or analytical perspective, using a range of methods, electrode types, and, supporting electrolytes [
Boron-doped diamond (BDD) is a very important material for electroanalysis, since it exhibits several electrochemically valuable properties such as its very wide electrochemical window in aqueous solutions resulting from the high overpotentials of the oxygen and hydrogen evolution reactions, low and stable voltammetric and amperometric background current, its excellent chemical and electrochemical stability in aggressive conditions, and its good responsiveness to a range of analytes without any conventional pretreatment [
Several important studies reported the determination of ASA in pharmaceutical formulations based on its hydrolysis to salicylate at controlled temperature conditions, using unmodified or modified graphite [
Published data reports the use of a boron-doped diamond (BDD) electrode for the electrochemical evaluation of salicylic acid in acidic media [
This paper presents the cyclic voltammetry (CV) investigation and the determination of acetylsalicylic acid by anodic differential pulse voltammetry (DPV) and chronoamperometry (CA), using a stationary mildly oxidized unmodified BDDE and a very simple and easy accessible supporting electrolyte, a neutral sodium sulphate solution. The actual report continues by outlining specific applications of DPV and CA techniques explored at a BDD electrode coupled with standard addition method to the analysis of two commercialized pharmaceutical formulations.
The electrochemical data were obtained from CV, DPV, and CA measurements. A Metrohm three-electrode cell equipped with a stabilized BDDE working electrode as a 3 mm diameter stationary disc embedded in a PEEK (PolyEtherEtherKetone) rod, a platinum foil counter-electrode, and a saturated calomel reference electrode (SCE), was used to perform the electrochemical measurements. The unmodified commercial boron-doped diamond electrode supplied by Windsor Scientific Ltd. for electroanalytical use was a mirror-polished doped polycrystalline industrial diamond (microcrystalline, doping degree cca. 0.1% boron) prestabilized in our laboratory by mild electrochemical oxidation at +2 V versus SCE in neutral and alkaline media and several hundreds repeated alternate polarization cycles between −1 and +2 V versus SCE in acidic and neutral media. All voltammograms were collected using an Autolab PGstat 20 EcoChemie system controlled by a PC running GPES Software version 4.9. The CV measurements obtained corresponded to restricted potential limits ranged between 0 V and +1.25 V versus SCE and a scan rate between 0.005 and 0.03 Vs−1, usually of 0.03 Vs−1. Working parameters for the exemplified differential pulse voltammograms involved a modulation time of 0.05 s, an interval time of 0.25 s, an initial potential of 0 V, an end potential of 1.25 V, a step potential of 0.00405 V, a modulation amplitude of 0.02502 V, and a scan rate of 0.0162 Vs−1. CVs, DPVs, and CAs were recorded at stationary electrode in quiescent solutions, in a controlled argon atmosphere, and at room temperature (
Before starting each series of electrochemical measurements, the working electrode was carefully cleaned, degreased, and treated to remove fouling by polishing with alumina aqueous suspension, and finally thoroughly washed with double-distilled water. Each determination was repeated three times with good reproducibility of the practically stabilized state of electrode surface recovered by simple means of cleaning of the electrode, short resting period, and brief stirring of the solution between the successive measurements.
The supporting electrolyte was a 0.1 M Na2SO4 unbuffered solution, pH practically 7. The substances used were analytical grade Merck reagents. Acetylsalicylic acid standard solutions were freshly prepared at room temperature (
The electroanalytical application of DPV and CA methods associated with standard addition method for detection and determination of acetylsalicylic acid was verified using
A series of cyclic voltammetry data recorded in a neutral unbuffered sodium sulphate solution used as supporting electrolyte represented the starting point in evaluating the electrochemical behavior of ASA at an unmodified BDDE. Figure
Cyclic voltammograms of 0.03 mM ASA. Supporting electrolyte: 0.1 M Na2SO4 pH 7; starting potential: 0 V versus SCE; potential range: 0 V → +1.25 V → 0 V versus SCE; scan rate: 0.03 Vs−1; (1)–(3): scan 1–scan 3.
The practical overlapping of second and third scans disposed below the first one corresponded to a stationary state of diffusively controlled anodic process. Voltammograms for ASA solutions, with anodic and cathodic branches (obtained but not presented here in the figures), corresponded to an irreversible electrochemical behavior of the studied compound at an unmodified BDDE. Our work relates only to the analytically oriented investigations without any consideration of the mechanistic aspects.
The influence of the scan rate on ASA anodic oxidation at BDDE in unbuffered 0.1 M Na2SO4 solution (pH 7) has been investigated for 0.03 mM ASA final concentration in the electrochemical cell, under cyclic voltammetric conditions. CV scans (see Figure
Cyclic voltammograms of 0.03 mM ASA. Effect of scan rate: (1) 0.005 Vs−1, (2) 0.01 Vs−1, (3) 0.015 Vs−1, (4) 0.02 Vs−1, (5) 0.025 Vs−1, (6) 0.03 Vs−1; supporting electrolyte: 0.1 M Na2SO4 pH 7; starting potential: 0 V versus SCE; potential range: 0 V → +1.25 V → 0 V versus SCE.
The diffusively controlled anodic oxidation process of ASA at BDDE and the absence of adsorbed reaction products on electrode surface were confirmed by the linear dependency and zero intercept of anodic current peak,
In addition, besides the good reproducibility and the detailed aspect regarding the control of anodic process by diffusion, the less positive potential of current peaks comparatively with literature data obtained at a strong oxidized BDD electrode [
ASA concentration effect (not presented here) on the optimum anodic response in CV exploration at an unmodified BDDE using a neutral sodium sulphate solution as supporting electrolyte was also evaluated. The series of CVs obtained for ASA standard solution were recorded over the concentration range of 0.01 mM–0.08 mM. Calibration plot data of anodic current peaks versus concentration of ASA exhibited good linearity and sensitivity (see Table
Parameters of calibration plots (
Figure | Method | Concentration range (mM) | Regression equation of linear calibration plot | Sensitivity ( | LOD ( | |
---|---|---|---|---|---|---|
— | CV | 0.01–0.08 | 24.175 | 0.998 | 1.02 | |
Figure | DPV | 0.01–0.1 | 12.86 | 0.998 | 1.03 | |
Figure | CA | 0.01–0.09 | 5.684 | 0.997 | 1.03 | |
Figure | CAa | 0.01–0.08 | 21.397 | 0.998 | 1.08 |
aContinuous addition, stirred solution.
After this preliminary discussion of cyclic voltammetry data, and confirmation of a diffusely controlled anodic process, more detailed investigations with electroanalytical application purposes were conducted using two other different techniques, differential pulse voltammetry, and chronoamperometry.
A series of anodic DPVs presented in Figure
Differential Pulse Voltammograms. Effect of ASA concentration: (1) supporting electrolyte, (2) 0.01 mM, (3) 0.02 mM, (4) 0.03 mM, (5) 0.04 mM, (6) 0.05 mM, (7) 0.06 mM, (8) 0.08 mM, (9) 0.09 mM, (10) 0.1 mM; supporting electrolyte: 0.1 M Na2SO4 pH 7.
Under conditions of the applied parameters of differential pulse voltammetry technique, sharp and well-defined current peaks corresponding to ASA oxidation manifested around +0.9 V versus SCE.
Calibration plot (for calibration data, see Table
The potential usefulness of DPV method at the determination of ASA content in real sample solutions was verified using aqueous solutions from tablets of
Figure
(a) Differential pulse voltammograms. (1) supporting electrolyte; (2) 0.2/50 dilution of
A similar evaluation, Figure
The matrix effects, which can be attributed to particular ingredients present in the tablets, were insignificant in their impact on quantitative evaluation of ASA in real samples.
The preliminary evaluation of cyclic voltammetric data for the detection and determination of acetylsalicylic acid at an unmodified BDDE using as supporting electrolyte a neutral unbuffered sodium sulphate solution, constituted, as already mentioned, a basis for the chronoamperometric study of ASA electrochemical behavior at the same working electrode.
The detailed investigation using the chronoamperometry (CA) method, similar to our former study [
Figure
Chronoamperograms. Effect of ASA concentration at one potential level, +0.9 V versus SCE, around the corresponding current peak potential from CVs. (1) supporting electrolyte, (2) 0.01 mM, (3) 0.02 mM, (4) 0.03 mM, (5) 0.04 mM, (6) 0.05 mM, (7) 0.06 mM, (8) 0.07 mM, (9) 0.08 mM, (10) 0.09 mM; supporting electrolyte: 0.1 M Na2SO4 pH 7.
The tested analyte was added in increasing concentration, from 0.01 mM to 0.09 mM, and chronoamperograms were recorded at one potential level, +0.9 V versus SCE, which corresponded to optimum ASA anodic amperometric signal. Calibration plot of anodic currents read at 120 s (a sufficient time period for obtaining a conventional steady state) versus ASA concentration (see Table
A continuous chronoamperogram (see Figure
Continuous chronoamperogram at one potential level, +0.9 V versus SCE, around the corresponding current peak potential from CVs; progressive addition of ASA in the concentration range of 0.01 mM–0.08 mM; supporting electrolyte: 0.1 M Na2SO4 pH 7; stirred solution.
Linear plot (for calibration data, see also Table
The utility of chronoamperometric method for the assessment of ASA in single component systems was suggested by the relatively high sensitivities, RSD values between 2 and 3%, and also by low values of limit of detection. Thus, the potential usefulness of the elaborated method was then verified by practical data of chronoamperometry associated with standard addition method obtained from ASA determination in real samples of
Figure
(a) Chronoamperograms, at one potential level, +0.9 V versus SCE. (1) supporting electrolyte; (2) 0.2/50 dilution of
The other example of ASA determination in pharmaceutical formulations refers to using of an
The association of differential pulse voltammetry, and chronoamperometry techniques with standard addition method proved to be very useful in analytical evaluation of both ASA-containing pharmaceutical products,
Linear calibration data and LOD values obtained are summarized in Table
The detection and determination of acetylsalicylic acid by differential pulse voltammetry and chronoamperometry using a mildly oxidized boron-doped diamond electrode and an easily accessible, simple unbuffered sodium sulphate solution as supporting electrolyte has been achieved.
Very good linearities of the calibration plots of anodic current peaks and anodic currents, respectively, versus ASA concentration resulted from DPV and CA data. Adjacent analytical data regarding RSD, LOD, and sensitivities were obtained.
The association of differential pulse voltammetric and chronoamperometric methods with standard addition method has been successfully used for a fast analytical evaluation of pharmaceutical formulations which contain acetylsalicylic acid without significant matrix effects. The average content of ASA in BAYER and SICOMED tablets, explored as real samples, was measured in good accordance with those indicated by the suppliers.