Carbon film resistor electrode for amperometric determination of acetaminophen in pharmaceutical formulations
Introduction
Acetaminophen (N-acetyl-p-aminophenol, 4-acetamido-phenol, paracetamol or tylenol) is a popular analgesic and antipyretic agent. Its action is similar to aspirin and is an appropriate alternative for patients who are sensitive to acetylsalicylic acid [1]. The development of analytical techniques for the rapid analysis of paracetamol is important for quality and medical control. Overdose ingestions of acetaminophen lead to accumulation of toxic metabolites, which may cause severe and sometimes fatal hepatotoxicity and nephrotoxicity [2], [3], [4]. This drug is available in different dosage forms of tablets, capsules, suspensions and suppositories.
Kissinger et al. [5], [6] investigated the electrochemical oxidation of acetaminophen through cyclic voltammetric studies. The first reaction step is an electrochemical oxidation involving two electrons and two protons to generate N-acetyl-p-quinoneimine. All subsequent reaction steps are non-electrochemical, but pH-dependent, processes. For oxidations at pH values ≥ 6, the final product is a benzoquinone.
For the quantification of acetaminophen in pharmaceutical products, the American Pharmacopoeia recommends liquid chromatography as the official method [7] while the Brazilian Pharmacopoeia uses a spectrophotometric technique [8]. Moreover, there are many studies described in the literature for determination of this drug.
These include spectrophotometry [9], [10], [11], chemiluminescence [12], [13], liquid chromatography [14], capillary electrophoresis [15], [16], amperometric biosensors [17], [18], [19], amperometric batch injection analysis [20], colorimetry [21], titrimetry [22] and FTIR-spectrometry [23]. Flow injection analysis (FIA) using UV–vis spectrophotometric detection has been demonstrated in several papers to be appropriate for acetaminophen determination [24], [25], [26], [27], [28], but these spectrophotometric methods require special reagents and are time consuming, not constituting a rapid analytical method.
Many voltammetric studies involving acetaminophen quantification utilize chemically modified electrodes [29], [30], [31], [32], [33] or boron doped diamond electrodes [34] in order to improve the sensitivity. To the best of our knowledge, there is no other report in the literature of flow injection studies utilizing unmodified electrodes for acetaminophen quantification in pharmaceutical formulations. The possible use of unmodified electrodes is an attractive alternative to investigate, since it leads to simplification of the analytical procedure and a decrease in analysis time, particularly in flow analysis.
This paper reports the electrochemical determination of acetaminophen in different pharmaceutical tablets at carbon film electrodes, without any sample pretreatment or electrode modification being necessary. These carbon film electrodes, fabricated from carbon resistors of 2 Ω nominal resistance, have a wide potential window (for both positive and negative limits) than many other forms of carbon, the detector preparation is very easy and they have already been employed in a variety of electroanalytical experiments involving its characterization [35], [36], trace metal analysis [37], [38] and its utilization for biosensor construction [39], [40], [41], [42]. Cyclic voltammetry characterization and determinations by flow injection analysis with amperometric detection were performed, at the carbon film electrode inserted in a flow cell. In the flow injection procedure, a wide linear working range, high sensitivity and submicromolar detection limit were achieved, without any memory effect between injections.
Section snippets
Reagents and solutions
Acetaminophen, caffeine, l-ascorbic acid, citric acid, lactose and glucose were obtained from Sigma (St. Louis, Mo, USA). Sodium hydroxide, sulphuric acid, sodium monohydrogen phosphate and potassium dihydrogen phosphate were acquired from Merck (Darmstadt, Germany). All aqueous solutions were freshly prepared by dissolving the solid salt in 0.1 mol L−1 phosphate buffer electrolyte solution. The pH (2–12) of the solutions was adjusted to the required value by addition of aliquots of 1.0 mol L−1
pH dependence study
The electrochemical behavior of acetaminophen was investigated over the pH range from 2 until 12. Fig. 2 shows cyclic voltammograms of 1.0 × 10−4 mol L−1 acetaminophen in 0.1 mol L−1 phosphate buffer solutions. It was observed that the oxidation potential decreased when the pH of the acetaminophen solution increased. This behavior was attributed to an increasing amount of hydrolysis that occurs as the pH is increased, leading to the formation of reducing compounds such as p-hydroxyaniline [34]. The
Conclusion
The results obtained in this work demonstrated the potentiality for carbon film resistor electrodes combined with FIA-amperometric detection for acetaminophen determination in pharmaceutical formulations. The high sensitivity provided by amperometry associated with the low cost of the sensor, makes this method very suitable for quality control applications. Moreover, carbon film electrodes provide good selectivity and excellent sensitivity for acetaminophen quantification in relatively complex
Acknowledgements
The authors gratefully acknowledge the financial support from Brazilian Foundations (FAPESP, CNPq, CAPES) and Fundação para a Ciência e Tecnologia (FCT) Portugal, ICEMS (Research Unit 103). This work was also partially supported with grants of IM2C project, RENAMI and SAMUTI projects.
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