Carbon film resistor electrode for amperometric determination of acetaminophen in pharmaceutical formulations

Abstract

Flow injection analysis (FIA) with amperometric detection was employed for acetaminophen quantification in pharmaceutical formulations using a carbon film resistor electrode. This sensor exhibited sharp and reproducible current peaks for acetaminophen without chemical modification of its surface. A wide linear working range (8.0 × 10⁻⁷ to 5.0 × 10⁻⁴ mol L⁻¹) in phosphate buffer solution as well as high sensitivity (0.143 A mol⁻¹ L cm⁻²) and low submicromolar detection limit (1.36 × 10⁻⁷ mol L⁻¹) were achieved. The repeatability (R.S.D. for 10 successive injections of 5.0 × 10⁻⁶ and 5.0 × 10⁻⁵ mol L⁻¹ acetaminophen solutions) was 3.1 and 1.3%, respectively, without any memory effect between injections. The new procedure was applied to the analyses of commercial pharmaceutical products and the results were in good agreement with those obtained utilizing a spectrophotometric method. Consequently, this amperometric method has been shown to be very suitable for quality control analyses and other applications with similar requirements.

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.