An electrochemical acetaminophen sensor based on La3+/Co3O4 nanoflowers modified graphite screen printed electrode architecture

Document Type: Reasearch Paper


1 Department of Chemistry, Shahid Bahonar University, Kerman, Iran.

2 Environment Department, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.


In this study, the La3+/Co3O4 nanoflowers were synthesized by co-precipitation method. The morphology of the La3+/Co3O4NFs were characterized using scanning electron microscopy (SEM), and were further used to modify the graphite screen printed electrode (GSPE). The electrochemical behavior of acetaminophen at La3+/Co3O4NFs/GSPE has been studied in aqueous solutions. Experimental results showed that the La3+/Co3O4NFs modified GSPE possess excellent electrocatalytic activity toward the detection of acetaminophen. Under optimum conditions, the La3+/Co3O4NFs modified electrode exhibited high sensitivity and stability to acetaminophen over a wide linear range of concentrations from 0.5μM to 250.0μM, with a detection limit of 0.09μM. Finally, the proposed sensor was successfully applied to the detection of acetaminophen in real samples.


Main Subjects


Recently the design, fabrication and application of novel electroanalytical methods for the analysis of electroactive materials in biological samples have received much interest due to less time consuming, rapid, simple, inexpensive, adequate accuracy and selectivity [1-7]. These features were attained by using modified electrodes as working electrodes in the potentiostatic systems by methods such as voltammetry and amperometry [8-11]. Nowadays, the nanoscale materials have been attracted much attention to modify on the surface of electrodes for electrochemical detection biological compounds due to their unique physical and chemical properties, such as large surface area, plenty active sites, high electronic conductivity and good chemical stability [12-24].

Lanthanides, as f-block-based elements, possess remarkable chemical and physical properties. Lanthanide-based materials have been used as sensing materials in electrode modifiers in voltammetric sensors. In voltammetric sensors, changes in the current produced by the targeted analyte due to redox events are measured as the potential of the working electrode is varied in a controlled way. Because many electroactive species are not able to have a good charge transfer on the electrode surfaces, there is a need to modify the electrode surface with a suitable material. Many Lanthanide-based materials have recently been used as modifiers in voltammetric sensing [25]. Lanthanum (La) is one of the most important lanthanides elements. La ions own relatively low toxicity and extraordinary catalytic properties, thus, those ions can be used to construct environment-friendly sensors [26-28]. Recently, transition metal oxides such as Co3O4 nanoparticles have been explored as the sensing materials for several biologically important analytes detection with satisfactory results due to their biocompability, good electrochemical properties, low cost, earth abundance, large surface area, wide availability and good ability of promoting electron transfer reactions [29-32].

Screen printing technology has been evolved for designing feasible disposable chemical sensors, which is involved in the fabrication of screen printed electrodes (SPEs) [33]. The use of screen printed electrodes for the recognition and determination of a variety of analytes is currently undergoing widespread growth. Screen printed electrodes have all the major performance characteristics of sensors: sample preparation is minimal; they are quick, cheap, and easy to use; and they are small and can be miniaturized with new technology [34-38].

Acetaminophen (N-acetyl-p-aminophenol or Paracetamol) (Fig. 1), is the most widely used analgesic and antipyretic drug in the world [39-40]. When it is used as an analgesic drug it reduces mild-moderate pain associated with headache, backache, muscular aches, toothache, migraine and postoperative pain. As an antipyretic agent it reduces fevers of viral and bacterial origin [41-42]. Limited use of acetaminophen does not exhibit any harmful side effects, while overdoses of acetaminophen will damage liver and kidney [43-44]. Thus, the development of efficient, sensitive, and simple analytical techniques for the determination of acetaminophen is important. A great number of analytical methods such as: high performance liquid chromatography (HPLC) [45], spectrofluorimetry [46], spectrophotometry [47], and electrochemical methods [48-51] have been developed for the determination of acetaminophen. The aim of this study is to develop a novel, simple, reliable electrochemical sensor for the determination of acetaminophen based on the co-precipitation synthesized La3+/Co3O4NFs modified graphite screen printed electrode (GSPE). The La3+/Co3O4NFs modified GSPE showed a better electrocatalytic redox behavior compared with unmodified GSPE. The prepared modified electrode (La3+/Co3O4NFs/GSPE) showed a good sensitivity and reproducibility. The proposed sensor was successfully applied to the determination of acetaminophen in acetaminophen tablet and urine samples.


Chemicals and Apparatus

Electrochemical measurements were done by an Autolab potentiostat/galvanostat (PGSTAT 302N, Eco Chemie, the Netherlands). Experimental conditions were controlled through General Purpose Electrochemical System (GPES) software. The screen printed electrode (DropSens, DRP-110, Spain) consists of three conventional electrodes: graphite counter electrode, a silver pseudo-reference electrode and an unmodified graphite working electrode. A Metrohm 710 pH meter was employed for pH measurements. La3+/Co3O4NFs were synthesized in our laboratory as described below.

The solutions were freshly prepared with double distilled water. Acetaminophen and all other reagents were of analytical grade and were purchased from Merck chemical company (Darmstadt, Germany). The buffer solutions were prepared from orthophosphoric acid and its salts in the pH range of 2.0-9.0.

Synthesis of La3+/Co3O4 nanoflowers

All the chemicals used for the preparation of the nano-powders, namely cobalt acetate (Co(CH3COO)2.2H2O), lanthanum nitrate (La(NO3)3. 6H2O), thiourea ((NH2)2CS) and ammonia (25% NH3), were of analytical grade. All the precursors were dissolved in deionized water. During the preparation of the nano-powders, ammonia was used as a complexing agent. The La3+-doped Co3O4nanostructures were prepared by dissolving 0.46 mol of cobalt acetate in 80 mL of deionized water, 0.0046 mol of lanthanum nitrate in 80 mL of deionized water, 0.18 mol of thiourea in 80 mL of deionized water and lastly by adding 19.76 mL of ammonia in 80 mL of deionized water. The amount of solutions of cobalt acetate, thiourea and ammonia was held constant at a ratio of 1 : 1 : 1. Then the cobalt acetate solution was added in a beaker in the reaction bath, followed by adding thiourea and lanthanum nitrate solution in the same reaction bath and the mixture was stirred for a few seconds. Lastly ammonia solution was added slowly into the mixture, while continuing stirring for 5 min. The temperature of the bath was then allowed to increase up to 80 °C. After that the precipitates were formed and were left overnight and filtered thereafter. The precipitates were then washed with ethanol. The obtained powders were dried at ambient conditions for several days. A typical SEM for synthesized La3+-doped Co3O4 nanoflowers is shown in Fig. 2.

Preparation of the electrode

The bare graphite screen printed electrode was coated with La3+/Co3O4 according to the following simple procedure. 1 mg La3+/Co3O4 was dispersed in 1 mL aqueous solution within 45 min ultrasonication. Then, 5 µl of the prepared suspension was dropped on the surface of carbon working electrodes. It remains at room temperature until becomes dry.

Preparation of real samples

Five acetaminophen tablets (labeled 300 mg per tablet, Amin Company, Iran) were grinding and homogenizing. Then, the tablet solution was prepared by dissolving 300 mg of the powder in 25 ml water by ultrasonication. Then, different volumes of the diluted solution were transferred into a 25 ml volumetric flask and diluted to the mark with PBS (pH 7.0). The acetaminophen content was analyzed by the proposed method using the standard addition method.

Urine samples were stored in a refrigerator immediately after collection. 10 ml of the sample was centrifuged for 15 min at 2000 rpm. The supernatant was filtered out using a 0.45 μm filter. Then, different volumes of the solution were transferred into a 25 ml volumetric flask and diluted to the mark with PBS (pH 7.0). The diluted urine sample was spiked with different amounts of acetaminophen.


Electrochemical behavior of acetaminophen on the La3+/Co3O4/GSPE

The electrochemical behavior of acetaminophen is dependent on the pH value of the aqueous solution.

Therefore, pH optimization of the solution is necessary in order to obtain the best results for electro-oxidation of acetaminophen. Thus the electrochemical behavior of acetaminophen was studied in 0.1 M PBS in different pH values (2.0-9.0) at the surface of La3+/Co3O4/GSPE by voltammetry (Fig. 3). It was found that the electro-oxidation of acetaminophen at the surface of La3+/Co3O4/GSPE was more favored under neutral conditions than in acidic or basic medium (Fig. 3 inset b). Thus, the pH 7.0 was chosen as the optimum pH for electro-oxidation of acetaminophen at the surface of La3+/Co3O4/GSPE. The mechanism for oxidation of acetaminophen is shown in Fig. 4.

In addition, the long-term stability of the La3+/Co3O4/GSPE was tested over a three-week period. When CVs were recorded after the modified electrode was stored in atmosphere at an ambient temperature, the peak potentials for acetaminophen oxidation were unchanged and the current signals showed less than 2.5% decrease relative to the initial response. The antifouling properties of the modified electrode toward acetaminophen and its oxidation product were investigated by recording the CVs of the modified electrode before and after use in the presence of acetaminophen. CVs were recorded in the presence of acetaminophen after having cycled the potential 20 times at a scan rate of 50 mVs-1. The peak potentials were unchanged and the currents decreased by less than 2.4%. Therefore, at the surface of La3+/Co3O4/GSPE, not only the sensitivity increases, but the fouling effect of the analyte and its oxidation product also decreases.

Fig. 5. depicts the CV responses for the electro-oxidation of 150.0μM acetaminophen at an unmodified GSPE (curve a), Co3O4/GSPE (curve b), and La3+/Co3O4/GSPE (curve c). The peak potential due to the oxidation of acetaminophen at the surface of La3+/Co3O4/GSPE (curve c) occurs at 390 mV, which is about 50 and 110 mV more negative than Co3O4/GSPE (curve b) and unmodified GSPE (curve a) respectively . Also, La3+/Co3O4/GSPE shows much higher anodic peak current for the oxidation of acetaminophen (4μA) compared to Co3O4/GSPE (3 μA) and unmodified GSPE (2 μA), indicating that the modification of unmodified GSPE with La3+/Co3O4NFs has significantly improved the performance of the electrode toward acetaminophen oxidation.

Effect of scan rate on the results

In the next experiment, the scan rate of the method was optimized to consider the response mechanism. Increasing in scan rate leads to enhancement of the oxidation peak current of acetaminophen. According to the obtained results from the study of the effect of potential scan rates on the oxidation currents of acetaminophen, Fig. 6, it can be concluded that there is a linear relationship between Ip and the square root of the potential scan rate (ν1/2). This demonstrates that the oxidation procedure of acetaminophen is a kind of diffusion control process.

Chronoamperometric analysis

The analysis of chronoamperometry for acetaminophen samples was performed by use of La3+/Co3O4/GSPE vs. Ag/AgCl/KCl (3.0 M) at 0.45V. The Chronoamperometric results of different concentration of acetaminophen sample in PBS (pH 7.0) are demonstrated in Fig. 7. The Cottrell equation for chronoamperometric analysis of electroactive moieties under mass transfer limited conditions is as follow [52]:

I =nFAD1/2Cbπ-1/2t-1/2

Where D represents the diffusion coefficient (cm2 s-1), and Cb is the applied bulk concentration (mol cm−3). Experimental results of I vs. t−1/2 were plotted in Fig. 6A, with the best fits for different concentrations of acetaminophen. The resulted slopes corresponding to straight lines in Fig. 6A, were then plotted against the concentration of acetaminophen (Fig. 6B). The mean value of D was determined to be 8.6×10−5cm2/s and according to the resulting slope and Cottrell equation.

Calibration plot and limit of detection

Fig. 8. showed the differential pulse voltammetric response of acetaminophen at La3+/Co3O4/GSPE in the phosphate buffer solution with pH=7.0. We found a relationship between the oxidation current of acetaminophen and its concentration within the range 0.5-250 µΜ. The detection limit (3σ) of acetaminophen was found to be 0.09 µΜ.

Table 1. shows a comparison of analytical properties for the detection of acetaminophen at the prepared electrode in this work and some other works.

Analysis of real samples

In order to evaluate the analytical applicability of acetaminophen, the proposed method, also it was applied to the determination of acetaminophen in acetaminophen tablet and urine, using a standard addition method. The results for determination of the acetaminophen in real samples are given in Table 2. Satisfactory recoveries of the experimental results were found for acetaminophen. The reproducibility of the method was demonstrated by the mean relative standard deviation (R.S.D.).


In conclusion, La3+/Co3O4NFs were used to modify the surface of the GSPE. A sensitive and reliable method to determine the acetaminophen in the real samples was firstly elaborated by the obtained La3+/Co3O4NFs/GSPE. The results indicated that the La3+/Co3O4NFs/GSPE exhibited a remarkable capacity to the electrochemical oxidation and reduction of the acetaminophen. Moreover, a linear relationship was observed between the response and the concentration in the range of 0.5 to 250.0 μM.


The authors declare that there is no conflict of interests regarding the publication of this manuscript.


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