Voltammetric determination of paracetamol at C60-modified glassy carbon electrode
Introduction
Paracetamol (N-acetyl-p-aminophenol) is a commonly used analgesic and antipyretic drug these days. Paracetamol acts as painkiller by inhibiting prostaglandin's synthesis in the central nervous system and relieves fever by sedating hypothalamic heat-regulating center [1]. Paracetamol, a weak acid having pKa value 9.5, rapidly gets absorbed and distributed after oral administration and is easily excreted in urine [2]. Generally paracetamol does not exhibit any harmful side effects but hypersensitivity or overdoses in few cases leads to the formation of some liver and nephrotoxic metabolites [3], [4]. Non-invasive methods (e.g. urine samples), with faster analysis and simple procedure, are given preferences inspite of the fact that the best way for clinical analysis is estimation of drug blood levels. Clinical analysis of paracetamol formulations using urinary excretion data has been well documented [5], [6], [7], [8], [9], [10], [11]. Attention of medical staff, discomfort and possible hazard of repeated venipunctures in analysis of drug blood level could be avoided using such methods. Criado et al. [12] described a fully automated urinary screening system for paracetamol and its metabolites, which comprises on-line acid microwave assisted hydrolysis of paracetamol to p-aminophenol followed by reaction with o-cresol in alkaline solution. The absorbance of indophenol blue dye formed is then monitored at 620 nm.
However, analytical methods get preference if they can be used without sample pre-treatment. Use of electrochemical methods in analysis attracted attention as an accurate, sensitive and cost-effective method of analysis in last decade. The electroanalytical features and performances of carbon paste electrodes for fabrication of chemo and biosensors through the modification of carbon paste and their analytical applications are well documented [13], [14], [15], [16], [17], [18]. In last few years, the modification of electrode surface attracted considerable attention because of the remarkably improved results achieved in such cases. Tan et al. [19] compared the electrochemical oxidation of l-cysteine on C60-modified carbon electrode with that on bare glassy carbon electrode and reported significantly better results for C60-modified electrode.
The present paper describes simple differential pulse voltammetric technique for the sensitive and selective determination of well-known analgesic drug paracetamol at C60-modified glassy carbon electrode at physiological pH, i.e. at pH 7.2. The electrode has a catalytic function towards the oxidation of paracetamol. Electrode modified using fullerene films [20] have been found to show much better results as compared to bare electrodes and have a lot of potential applications in electroanalytical studies. The method described in this paper overcomes the two major limitations of conventional methods for the screening of paracetamol and its metabolites in urine samples, namely the hydrolysis time and the interference. Further, the method does not require any sample pre-treatment.
The proposed method also resolves the voltammetric response of the paracetamol and p-aminophenol in two well-defined voltammetric peaks. The voltammetric response of paracetamol in the presence of other interferents, viz., ascorbic acid, caffeine, glucose and urea has also been studied. Various paracetamol containing tablets and syrup were also examined for their paracetamol content and experimental determinations are in good agreement with the reported paracetamol in them.
Section snippets
Chemicals and reagents
C60-fullerene was obtained from Aldrich, USA (purity 98%). Pure paracetamol in powdered form was obtained as a gift sample from Sri Krishna Pharmaceuticals Ltd., Hyderabad. Ascorbic acid, caffeine, glucose and urea were purchased from E. Merck. p-Aminophenol was obtained from Loba Chemie and was recrystallised before use. Paracetamol containing tablets and syrup marketed by different medical companies were purchased from the local market. Phosphate buffer solutions (μ = 1.0 M) were prepared
Electrochemical oxidation of paracetamol
A remarkable improvement in electrode response was observed at fullerene-C60-modified GCE towards oxidation of paracetamol as fullerene anion (C60n−) catalyses redox reaction as it makes deprotonation of substrate easier [22]. Fig. 1 illustrates the voltammogram of paracetamol at bare and C60-modified GCE at pH 7.2. As compared to bare GCE, the electrooxidation of paracetamol occurred at a lesser potential with enhanced peak current at C60-modified electrode. Appearance of oxidation peak at
Conclusions
Many analytical methods are employed for quality control, stability testing, identification and clinical studies before bringing a drug product from the discovery stage to the commercial market. Analysts choose from a number of techniques, such as NMR, MS, separations, spectroscopy and electrochemistry, each having its own advantages. Electrochemistry has many advantages making it an appealing choice for pharmaceutical analysis. Most electrochemical techniques have excellent detection limits
Acknowledgements
One of the authors (SPS) is thankful to the Council of Scientific and Industrial Research for awarding Junior Research Fellowship. Financial assistance for this work was provided by CSIR, New Delhi vide grant no. 01(1815)/02/EMR-II.
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