Magnetic nanoparticles incorporated on functionalized mesoporous silica: an advanced electrochemical sensor for simultaneous determination of amiodarone and atenolol

Abstract

A new chemically modified carbon paste electrode is constructed based on magnetic (Fe₂O₃) mobile crystalline material-41 grafted with 3-aminopropyl groups (MCM-41–nPrNH₂), a kind of mesoporous silica with large surface area (362 m² g⁻¹). For the first time, the electrode was evaluated as an electrochemical sensor for simultaneous determination of amiodarone and atenolol in aqueous solutions. The measurements were carried out by application of the differential pulse voltammetry method in Briton Robinson buffer solution with pH 4.00. Fe₂O₃ loaded in MCM-41–nPrNH₂ can increase anodic peak currents by adsorption of amiodarone and atenolol on the electrode surface. The prepared electrode shows voltammetric responses with good selectivity for amiodarone and atenolol in optimal conditions, which makes it suitable for simultaneous determination of these drugs.

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Introduction

Recently, mesoporous molecular sieves have attracted significant attention in the field of electrochemical sensing as they exhibit excellent characteristics such as a high surface area up to 1500 m² g⁻¹, a large pore volume, and a narrow pore size distribution between 1.5 and 10 nm.¹ In addition, they are highly efficient, sustainable, recyclable, and eco-friendly materials. Mobile crystalline material-41 (MCM-41) is a mesoporous material consisting of a hexagonal array of unidirectional pore structures which is synthesized under basic conditions using cationic surfactants as structure-directing agents. Pure MCM-41 is neutral in charge and exhibits only weak hydrogen-bonding type sites which limit its application in sensing.² The functional aminopropyl group was anchored on MCM-41 silica by the post-modification method and was prepared according to the procedure reported in the literature from the reaction of MCM-41 with 3-aminopropyltriethoxysilane in refluxing dry toluene.³

The integration of functionalized mesoporous silica with magnetic nanoparticles to form a porous magnetic nanocomposite is undoubtedly of great interest for practical applications. These types of magnetic nanocomposites have the advantages of both mesoporous silica and magnetic nanoparticles. Also magnetic separation by an appropriate magnetic field provides a convenient and low cost method for the separation of these magnetic catalysts in a multiphase suspension without using extra organic solvents and additional filtration steps or tedious work-up.^4,5

Determination and quantification of drugs in biological fluids and pharmaceutical samples are essential in clinical chemistry, toxicological, doping and pharmaceutical investigations. On the other hand, the therapeutic efficacies of drugs are related to their concentrations in biological fluids (mostly plasma). Therefore, the simpler and more rapid methods for simultaneous analyses of several drugs are interesting for therapeutic drug monitoring purposes. Despite their widespread application and use, little work has been reported on the simultaneous determination of cardiovascular drugs by electrochemical and related sensing devices.⁶

Electrochemical techniques have been used for the determination of a wide range of drug compounds, often without derivatization. Additionally, electrochemical techniques include the determination of the drug's electrode mechanism. Redox properties of drugs can provide insight into their metabolic fate, their in vivo redox processes and their pharmacological activities.^7–9 For that reason, it is important to find out more sensitive sensors for detection of these drugs. As far as we are aware, not only is there no report on the preparation of magnetic mobile crystalline material-41–nPrNH₂ (Fe₂O₃–MCM-41–nPrNH₂) modified electrode but also, there is no report on simultaneous determination of amiodarone (AM) and atenolol (AT) by electrochemical methods. Therefore, based on the importance of simultaneous determination of these drugs, in the present work, we constructed a new magnetic sensor for simultaneous detection of AM and AT. The present study was an attempt on the development and application of the modified electrodes which were aimed at inspecting the electrochemical processes of two cardiovascular drugs. In this paper, we demonstrated the first application of Fe₂O₃–MCM-41–nPrNH₂ for simultaneous determination of AT and AM in aqueous solutions.

Experimental details

Chemicals and materials

All chemicals were purchased from Merck (Darmstadt, Germany) and were used without further purifications. AM and AT were kindly gifted by Sobhan Darou Co., (Rasht, Iran). All solutions were prepared with double distilled water. Before spiking the samples with AM and AT, these drug solutions were filtered, and diluted 2 times with a 0.15 M Briton Robinson buffer (pH 4.00). Briton Robinson buffer was prepared by initially dissolving 10.1 mL concentrated orthophosphoric acid, 8.7 mL glacial acetic acid and 9.27 g boric acid in water and diluting to 1.0 L in a volumetric flask. This solution was subsequently used to prepare appropriate buffers.

To prepare the solutions of the AM and AT commercial samples, a representative number of tablets (10) of each different pharmaceutical dosage were reduced to a homogeneous fine powder in a mortar with a pestle. An adequate amount of the resulting powders was weighed and transferred to a 25 mL calibrated flask, which was completed to volume with the respective supporting electrolyte solution. An aliquot of each sample solution was directly transferred to the electrochemical cell containing the respective supporting electrolyte, after which the voltammograms were obtained.

Instrumentation

Electrochemical measurements were carried out in a conventional three-electrode cell containing 0.15 M Briton Robinson buffer of pH 4.00 (which was employed as the running electrolyte throughout the work) powered by a Potentiostat/Galvanostat, an Autolab, and PGSTAT 302N (Eco Chemie, the Netherlands). Ag/AgCl and Pt wire were used as the reference and counter electrodes, respectively. The system was run by a PC through NOVA software.

IR spectra were recorded on a Shimadzu model FTIR prestige 21 spectrophotometer (Tokyo, Japan) using KBr discs. Additional dilute solutions were prepared daily by accurate dilution just before use. The drug solutions were stable and their concentrations did not change with time. X-ray powder diffraction (XRD) measurements were performed using a Philips diffractometer manufactured by X'Pert with monochromatized CuKα radiation. The pore structure of the prepared catalyst was verified by the nitrogen sorption isotherm ([5.0.0.3] Belsorp, BEL Japan, Inc.).

Procedures

Synthesis of (Fe₂O₃)–MCM-41–nPrNH₂. Briefly naked Fe₃O₄ nanoparticles were prepared from a solution with molar composition of 3.2FeCl₃ : 1.6FeCl₂ : 1CTAB in NH₄OH/H₂O (39 : 2300) at room temperature. Typically, 2 g of iron(III) chloride (FeCl₃·6H₂O) and 0.8 g of iron(II) chloride (FeCl₂·4H₂O) were dissolved in 10 mL of distilled water under a N₂ atmosphere. The resultant solution was added dropwise to a 100 mL solution of 1.0 M NH₄OH containing 0.4 g of CTAB to construct a colloidal suspension of iron oxide magnetic nanoparticles. The magnetic MCM-41 (Fe₂O₃–MCM-41) was prepared by adding 20 mL of the magnetic colloid to a 1 L solution with the molar composition of 292 NH₄OH : 1 CTAB : 2773 H₂O under vigorous mixing and sonication. Then sodium silicate (16 mL) was added, and the mixture was allowed to react at room temperature for 24 h under stirring. The Fe₂O₃–MCM-41 was filtered and washed with alcoholic ammonium nitrate. The surfactant template was then removed from the synthesized material by calcination at 450 °C for 4 h and the Fe₃O₄–MCM-41 converted to Fe₂O₃–MCM-41. It is worth mentioning that in the absence of nitrogen the magnetic properties of Fe₃O₄ are decreased. Then, functionalized Fe₂O₃–MCM-41 [Fe₂O₃–MCM-41–nPrNH₂] was prepared from the reaction of (Fe₂O₃)–MCM-41 with 3-aminopropyltriethoxysilane by refluxing in dry toluene.

Unmodified carbon paste electrode (UCPE) was prepared by hand-mixing carbon powder and mineral oil (80 : 20 w/w%) ratio. The paste was carefully mixed and homogenized in an agate mortar for 20 min. The resulting paste was kept at room temperature in a desiccator. The paste was packed firmly into a cavity (2 mm diameter, geometric surface area of 0.0125 cm² and 0.5 mm depth) at the end of a Teflon tube. Electrical contact was established via a copper wire connected to the paste in the inner hole of the tube. The electrode surface was gently smoothed by rubbing on a piece of weighting paper just prior to use. This procedure was also used to regenerate the surface of the carbon paste electrode (CPE). The Fe₂O₃–MCM-41–nPrNH₂–CPE was prepared by mixing carbon powder together with Fe₂O₃–MCM-41–nPrNH₂ at different ratios in an agate mortar until a uniform paste was obtained. The percentage (w/w) of Fe₂O₃–MCM-41–nPrNH₂ presented throughout the text corresponds to the final percentage relative to the total paste composition. Then mineral oil was added (20 w/w%) and mixed thoroughly. The paste obtained was packed into a 2 mm diameter cavity at the end of a Teflon tube, and the electrical contact was provided with a copper wire.

Results and discussion

Characterization of (Fe₂O₃)–MCM-41–nPrNH₂

The prepared magnetic nanocatalyst was characterized by transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, XRD, and nitrogen physicosorption measurements.

The TEM images showed that the encapsulated nanoparticles were present as uniform particles and the size of encapsulated nanoparticles was about 100 nm. Fig. 1 shows TEM images of mesoporous (Fe₂O₃)–MCM-41–nPrNH₂ in which all the materials possess hollow structures. They provide a large active surface area for the electrochemical measurements of AM and AT.

Fig. 1 TEM images of (a) (Fe₂O₃)–MCM-41 and (b) (Fe₂O₃)–MCM-41–nPrNH₂.

The IR spectra of Fe₂O₃–MCM-41 before and after functionalization are shown in Fig. 2. In the IR spectra, the band from 400–650 cm⁻¹ is assigned to the stretching vibrations of the (Fe–O) bond in Fe₂O₃, and the band at about 1100 cm⁻¹ belongs to the stretching of the (Si–O) bond. After functionalization with amine groups, the absorption bands at 1550 cm⁻¹ and at 1650 cm⁻¹ belong to the bending vibration of N–H groups. It should be mentioned that the C–N stretching vibrations in the region of 1030–1230 cm⁻¹ overlap with the broad absorption band of the silanol group and the Si–O–Si vibrations.

Fig. 2 FT-IR spectra of (a) Fe₂O₃–MCM-41 and (b) Fe₂O₃–MCM-41–nPrNH₂.

The XRD analysis of prepared catalyst was performed from 2.0° (2θ) to 80.0° (2θ). In the region of 2.0° (2θ) to 10.0° (2θ), the sample of (Fe₂O₃)–MCM-41–nPrNH₂ showed relatively well-defined XRD patterns, with one major peak along with two small peaks identical to those of MCM-41 materials. In addition, the XRD pattern in the region of 10.0° (2θ) to 80.0° (2θ) confirmed that the change of sample color from black to brick-red after calcination of the catalyst is due to the oxidation of embedded Fe₃O₄ to Fe₂O₃ nanoparticles (Fig. 3).

Fig. 3 The XRD pattern of prepared catalyst in the region of 2.0° (2θ) to 80.0° (2θ). Inset: catalyst recovery at the reaction.

The surface area and pore-size distribution of prepared materials were calculated from N₂ adsorption–desorption isotherms using the Brunauer, Emmett and Teller (BET),¹⁰ and Barrett, Joyner and Halenda (BJH)¹¹ methods, respectively (Fig. 4). For (Fe₂O₃)–MCM-41, a BET surface area of 1213 m² g⁻¹; pore volume of 1.29 cm³ g⁻¹; and average pore diameter of 5.26 nm were obtained. On the other hand, for (Fe₂O₃)–MCM-41–nPrNH₂, a BET surface area of 362 m² g⁻¹; pore volume of 0.35 cm³ g⁻¹; average pore diameter of 3.93 nm were calculated. These results show that the surface area and pore volume of functionalized magnetic MCM-41 were lower than those of corresponding mesoporous silica due to the grafting of nPrNH₂ groups.

Fig. 4 (a) Nitrogen adsorption–desorption isotherm, (b) BJH and (c) pore size distribution of Fe₂O₃–MCM-41–nPrNH₂.

Electrochemical behavior of AM and AT

Fig. 5 shows cyclic voltammograms of UCPE (curve a), MCM-41–nPrNH₂–CPE (curve b) and Fe₂O₃–MCM-41–nPrNH₂–CPE (curve c) in the presence of 15 μM AM and AT in 0.15 M Briton Robinson buffer (pH 4.00) solution. Fig. 5 (curve a) does not show an oxidation signal on UCPE. This indicated the electro-inactivity of AM and AT on the carbon paste surface. Typical cyclic voltammograms of MCM-41–nPrNH₂–CPE and Fe₂O₃–MCM-41–nPrNH₂–CPE in 0.15 M Briton Robinson buffer solutions and in the potential range of −0.5 to 1 V are shown as curves (b) and (c) in Fig. 5 where a potential sweep rate of 50 mV s⁻¹ has been employed. A number of well-defined peaks are observed in both MCM-41–nPrNH₂–CPE and Fe₂O₃–MCM-41–nPrNH₂–CPE electrodes. At both electrodes peak I at 0.066 V which related to MCM-41–nPrNH₂ was observed. Comparing to the MCM-41–nPrNH₂–CPE, Fe₂O₃–MCM-41–nPrNH₂–CPE shows another two anodic peaks which related to oxidation of AM and AT, respectively. Peaks II and III are assigned to AM and AT oxidation at the working pH, respectively. It is noteworthy to point out that the present response of AT and AM on Fe₂O₃–MCM-41–nPrNH₂–CPE was dramatically improved when Fe₂O₃ was introduced to the surface of MCM-41–nPrNH₂–CPE. There is ample evidence in the literature regarding the role of Fe(II) and (III) species in the oxidation of organic substrates.^12–17 These species that are generated at positive potentials have been reported to have the role of a redox mediator in the oxidation of several compounds at Fe related electrodes and the electrode reaction may take place with a mechanism involving a rate limiting step where a reaction intermediate is formed upon a chemical reaction with Fe(II) and (III) species. Due to the above results, MCM-41–nPrNH₂ provides an ideal platform to disperse Fe₂O₃ paramagnetic centers as much as possible because of the very large surface areas, diverse pore structures, tunable pore sizes and satisfactory biocompatibility.¹⁸ Considering these two factors, if the Fe₂O₃ paramagnetic centers were distributed evenly within a mesopore system, such a pore system could enable drugs to diffuse freely in mesopores with greatly increased accessibility to interact with Fe₂O₃ paramagnetic centers, which may result in the improved longitudinal relaxivity.

Fig. 5 Cyclic voltammograms of 15 μM AM and AT at the surface of the CPE (a), MCM-41–nPrNH₂–CPE (b) and Fe₂O₃–MCM-41–nPrNH₂–CPE (c) in BRB (pH 4) at a scan rate of 50 mV s⁻¹.

The differential pulse voltammograms (DPV) recorded for AM and AT at MCM-41–nPrNH₂–CPE and Fe₂O₃–MCM-41–nPrNH₂–CPE in 0.15 M Briton Robinson buffer (pH 4.00) are shown in Fig. 6A. As seen in Fig. 6A the DPV of AM and AT at Fe₂O₃–MCM-41–nPrNH₂–CPE showed excellent improvement in oxidation peak currents for these drugs. Therefore it is suggested that the application of Fe₂O₃–MCM-41–nPrNH₂–CPE leads to provide a current sensitivity and selectivity in simultaneous detection of AM and AT.

Fig. 6 (A) DPVs of MCM-41–nPrNH₂ (curve a) and Fe₂O₃–MCM-41–nPrNH₂ (curve b) containing 15 μM AM and AT. Solution: 0.15 M BRB (pH 4). Pulse amplitude: 0.05 V. Pulse width: 0.05 s. Pulse period: 0.2 s. (B) Effect of pH on the peak currents of oxidation of AM and AT compounds at Fe₂O₃–MCM-41–nPrNH₂–CPE in BRB (pH 4). Concentrations: 15 μM AM and AT. (SD = 3.0%, n = 3).

Effect of operational parameters

Effects of pH. Since the oxidation of the selected analytes is pH dependent, in order to optimize operational conditions and obtain the best peak separation and higher response, the effects of pH on the electrochemical response of the Fe₂O₃–MCM-41–nPrNH₂–CPE towards the simultaneous determination of AM and AT were investigated. Variations of peak current with respect to pH of the electrolyte (from 2.00 to 8.00) are shown in Fig. 6B. It can be realized that the anodic peak currents of AM and AT are increased slightly – when there is an increase in the pH solution until 4.00. Therefore the optimum solution pH selected was pH 4.00. The results indicated that all the anodic peak currents for the oxidation of AM and AT shifted towards more negative potential with an increase in pH. This result indicated that the protons have taken part in their electrode reaction processes.

Our results revealed that the numbers of protons in the processes are equal to the number of the transferred electrons which is in agreement with the known electrochemical reactions of AM and AT as shown in other investigations.^12–17 It is known that AT can be oxidized via a two electron and two proton process. Also, as shown in Scheme 1, AM can be oxidized via a one electron and one proton process, respectively.

Scheme 1 Oxidation mechanism of AT (A) and AM (B).

Effect of modifier percent. The effect of Fe₂O₃–MCM-41–nPrNH₂ as a modifier in the composition of the electrode is shown in Fig. 7. The results showed that the anodic peak current of AM and AT reached the highest value at 20% (w/w) of the modifier. Higher concentration of modifier showed a decrease in peak current. This is presumably due to reduction of conductivity of the electrode due to a decrease in graphite powder concentration. Consequently a carbon paste composition of 20% modifier, 50% graphite and 30% mineral oil was used in further studies. In addition, Fig. 7 shows when further increasing the content of Fe₂O₃–MCM-41–nPrNH₂ from 15% to 20%, the oxidation peak current of the drugs increases slightly, and the plot becomes curved. Indeed with increasing the content of Fe₂O₃–MCM-41–nPrNH₂, the effective surface area is improved and then the oxidation peak current is enhanced. However, the oxidation peak current of AM and AT dramatically decreases when the content of Fe₂O₃–MCM-41–nPrNH₂ increases from 20% to 25%, suggesting that too much Fe₂O₃–MCM-41–nPrNH₂ is not beneficial for AM and AT sensing. Although Fe₂O₃–MCM-41–nPrNH₂ possesses promising properties, its electric conductivity is very poor. So, the conductivity of the Fe₂O₃–MCM-41–nPrNH₂ sensor will gradually lower with increasing the content of Fe₂O₃–MCM-41–nPrNH₂, blocking the electron transfer and increasing the background current. As a result, the oxidation peak current of AM and AT contrarily decreases when the content of Fe₂O₃–MCM-41–nPrNH₂ is higher than 20%. In this work, the best content of Fe₂O₃–MCM-41–nPrNH₂ is selected as 20% (w/w).

Fig. 7 Effect of modifier percent on the peak current of 15 μM AM and AT at an accumulation time of 50 s (SD = 3.0%, n = 3).

Linear range, detection limit

Possible mutual interferences due to AM–AT interactions were investigated by changing the concentration of one drug at a constant concentration of the other drug. To verify the linear relationship between anodic peak currents and AM and AT concentrations, several calibration curves were constructed under optimum conditions in 0.15 M Briton Robinson buffer (pH 4) solutions. Fig. 8 shows DPVs obtained at Fe₂O₃–MCM-41–nPrNH₂–CPE in various concentrations of AM and AT. Fig. 8A shows DPV at various concentrations of AT in the presence of 15 μM AM. A linear dynamic range from 8 to 205 μM, with a calibration equation of I_p (μA) = 14.8c (μM) + 0.93 (R² = 0.990), and a detection limit of 2.1 μM (S/N = 3) was obtained. A linear relationship was found for AM in the 4.5–710 μM range containing 15 μM AT with a calibration equation of I_p (μA) = 11.0 (μA μM⁻¹) + 4.16 (R² = 0.991) and a detection limit of 1.4 μM (Fig. 8B). The values of the analytical parameters obtained for these drugs according to this method are reported in Table 1. Also, the results obtained for AM and AT on an (Fe₂O₃)–MCM-41–nPrNH₂–CPE are compared in Table 2 with previously reported methods for AM and AT detections.^19–30 It can be seen that the Fe₂O₃–MCM-41–nPrNH₂–CPE offered a reasonable linear range for AM and AT detections and the detection limit was lower than some of the previous reports. These results indicated that Fe₂O₃–MCM-41–nPrNH₂–CPE is an appropriate platform for the determination of AM and AT.

Fig. 8 (A) Differential pulse voltammograms for 10 (a), 15(b), 20 (c), 25 (d) and 30 (e) μM of AT in the presence of 15 μM AM. (B) Differential pulse voltammograms for 10 (a), 15 (b), 20 (c), 25 (d) and 30 (e) μM of AM in the presence of 15 μM AT.

Table 1 Parameters determined for calibration curves of drugs and accuracy and precision (n = 3) for electrocatalytic oxidation of drugs on (Fe₂O₃)–MCM-41–nPrNH₂ electrode

Analytical parameters	AM	AT
a Each value was obtained from ten experiments.b LOD: limit of detection; LOQ: limit of quantitation; RSD: relative standard deviation.
Linear range (μM)	4.5–710	8–205
Slope (μA μM^−1)	11.0	14.8
Intercept (μM)	4.16	0.93
RSD^a^b (%)	3.8	4.0
LOD^b (μM)	1.4	2.1
LOQ^b (μM)	3.4	6.0
Bias (%)	2.23	4.17

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Table 2 Results obtained from AM and AT analysis using several methods

Drug type	Method	Linear range	LOD	Ref.
AT	SWV	2.0–41 μM	0.93 μM	21
	DPV	2.0–41 μM	1.3 μM
	DSC	20–200 μM	1.8 μM	22
	DPV	0.25–1.5 mM	0.16 mM	23
	DPV	0.5–1000 μM	0.13 μM	24
	DPV	4–100 μM	3.16 μM	25
	Amperometry/FIA system	0.2–3 mM	18.1 μM	26
	DPV	12–96 μM	1.12 μM	27
	DPV	1.96–900 μM	0.07 μM	28
AM	ASV	0.2–23 nM	0.15 nM	29
	Potentiometric	6.2–2000 μM	4.7 μM	30
	DPV	0.2–4 μM	0.03 μM	31
	LSP	0.1–2 μM	0.05 μM	32
AT	DPV	8–205 μM	1.4 μM	This work
AM		4.5–710 μM	2.1 μM

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Reproducibility and long-term stability of the electrode

The reproducibility and stability are the two important parameters for the evaluation of the performance of a sensor. The main advantage of using the Fe₂O₃–MCM-41–nPrNH₂–CPE is easy and quick surface renewal after each use. Thus, the repeatability of the analytical signal has been studied. Indeed, the relative standard deviation (RSD) of 4.8% and 4.0% for 15 μM AM and AT, respectively, in ten consecutive determinations, has been obtained.

Another benefit of the proposed modified electrode was that this one showed good long term stability. Stability of the proposed electrode was tested by measuring the decrease in voltammetric current during repetitive DPV measurements of AM and AT with Fe₂O₃–MCM-41–nPrNH₂–CPE stored in solution or air. For example, this electrode, within 24 h, is used for the determination of 15 μM AM and AT in 0.15 M Briton Robinson buffer (pH 4.00). Obtained results show that this electrode has remarkable stability and any significant change in the voltammetric currents was not shown. When the electrode was stored in the atmosphere, the current response remained almost unchanged for 17 days. The high stability of the Fe₂O₃–MCM-41–nPrNH₂–CPE could be related to the strong affinity of MCM-41–nPrNH₂ for Fe₂O₃ and the insolubility of the MCM-41–nPrNH₂ in water.

Analytical application

Applicability of the Fe₂O₃–MCM-41–nPrNH₂–CPE was examined for the determination of AM and AT in commercial tablets by using differential pulse voltammetry (DPV), since DPV possesses high sensitivity and excellent resolution. The DPVs were obtained at Fe₂O₃–MCM-41–nPrNH₂–CPE by spiking appropriate samples in diluted solution, at optimum conditions, as described earlier. The results are presented in Table 3. The recoveries were acceptable, showing that the proposed methods could be efficiently used for the determination of lower concentration of these drugs in pharmaceutical preparations.

Table 3 Determination of AM and AT in commercial tablets by Fe₂O₃–MCM-41–nPrNH₂ electrode

Sample	Original	Added (μM)	Found (μM)	Recovery (%)
In commercial tablets	AM	0	—	—
		10	17.3	98.2
		40	54.5	102.5
	AT	0	—	—
		10	16.0	105.7
		40	60.3	103.7

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Fe₂O₃–MCM-41–nPrNH₂–CPE presents some advantages compared with other reported electrodes such as: simplicity and low cost construction, good LOD and selectivity as well as a wide linear range. In terms of LOD; the proposed sensor possesses an LOD of 1.4 μM and 2.1 μM for AM and AT, respectively whereas other electrodes provided lower LODs. But Fe₂O₃–MCM-41–nPrNH₂–CPE provided a wide linear range for detection of these drugs. Generally, it can be seen that the Fe₂O₃–MCM-41–nPrNH₂–CPE offered a reasonable linear range for AM and AT detections and the detection limit was lower than some of the previous reports. These results indicated that Fe₂O₃–MCM-41–nPrNH₂–CPE is an appropriate platform for the determination of AM and AT.

With the manufacture of more AM and AT electrochemical sensors, it was found that AM and AT has lower detection potentials on Fe₂O₃–MCM-41–nPrNH₂–CPE which is important in practical chemical analyses. So the detection of AM and AT by Fe₂O₃–MCM-41–nPrNH₂–CPE is appropriate. Also, MCM-41 is better than CNTs as MCM-41 is obtained more easily.

Conclusions

In the present study, for the first time, a sensitive, inexpensive, rapid and selective method for simultaneous determination of AM and AT was proposed based on electrocatalytic oxidation of the proposed analytes on the Fe₂O₃–MCM-41–nPrNH₂–CPE. The results indicated that Fe₂O₃–MCM-41–nPrNH₂–CPE facilitates the simultaneous determination of AM and AT with good sensitivity and selectivity. The electrode is stable in repetitive experiments due to the high affinity of MCM-41–nPrNH₂ for Fe₂O₃ and the low solubility of the MCM-41–nPrNH₂ in water. The proposed electrode was used for determination of AM and AT in commercial tablets, without the necessity for sample pretreatment or any time-consuming extraction or evaporation steps prior to the analysis, with satisfactory recovery. We used the mixture of AM and AT as a model mixture. However, the proposed electrode could be also used for determination of AM and AT in their individual pharmaceutical products. These types of analyses are in demand in the pharmaceutical industry for quality control of drugs. The reproducibility, good stability, wide linear range, low detection limit, and a distinct advantage of polishing in the event of surface fouling, suggest that this electrode is an attractive candidate as a transducer for practical applications. Also due to the very large surface area of MCM-41–nPrNH₂ and remarkable electrocatalytic properties of Fe₂O₃ the MCM-41–nPrNH₂–CPE can be used for simultaneous determination of some drugs which is necessary for interference studies.

Acknowledgements

This is a report of a database from thesis entitled "Development of sensitive, routine and reliable methods for determination of cardiovascular drugs in biological samples” registered in Drug Applied Research Center. We gratefully acknowledge the partial financial support of this work by the Drug Applied Research Center, Tabriz University of Medical Sciences.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3ra45433a

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