Simple flow injection amperometric system for simultaneous determination of dipyrone and paracetamol in pharmaceutical formulations

J. Braz. Chem. Soc., Vol. 20, No. 7, 1249-1255, 2009. Printed in Brazil - ©2009 Sociedade Brasileira de Química 0103 - 5053 $6.00+0.00 Wallans T. P. dos Santos, Denise T. Gimenes, Edimar G. N. de Almeida, Sebastião de P. Eiras, Yaico D. T. Albuquerque, Eduardo M. Richter* Instituto de Química, Universidade Federal de Uberlândia, Av. João Naves de Ávila, 2121, 38408-970 Uberlândia-MG, Brazil Este trabalho descreve uma metodologia simples empregando análise por injeção em fluxo com detecção amperométrica pulsada para determinação simultânea de dipirona (DI) e paracetamol (PCT) em formulações farmacêuticas. Os compostos são detectados através da aplicação de quatro pulsos de potencial (seqüenciais) em função do tempo. Dipirona é diretamente detectada em +0,40 V e paracetamol indiretamente em 0,00 V através da redução do produto de oxidação (N-acetil-pbenzoquinonaimina) gerada eletroquimicamente em +0,65 V. O quarto pulso de potencial (–0,05 V) é aplicado para a regeneração ou limpeza do eletrodo de trabalho (carbono vítreo). A faixa linear de resposta foi otimizada em 9 a 45 mg L-1 para dipirona e em 6 a 30 mg L-1 para paracetamol. As regressões lineares para as duas curvas analíticas apresentaram excelentes coeficientes de correlação (R = 0,999), assim como os resultados obtidos nos estudos de adição-recuperação (ca. 100%). A freqüência analítica para a metodologia proposta foi calculada em 45 injeções hora com o consumo de 1,5 mL de solução por minuto. O desvio padrão relativo do sinal para 24 injeções sucessivas foi calculado em 0,4 % para dipirona e 0,2 % para paracetamol. O método proposto foi usado com sucesso para a determinação destes compostos em formulações farmacêuticas. In this work a simple flow injection methodology with pulsed amperometric detection for simultaneous determination of dipyrone (DI) and paracetamol (PCT) in pharmaceutical formulations is described. The compounds are detected by applying four sequential potential pulses as function of the time. Dipyrone is directly detected at +0.40 V and paracetamol indirectly at 0.00 V through the reduction of the oxidation product (N-acetyl-p-benzoquinoneimine) electrochemically generated at +0.65 V. The fourth potential pulse (–0.05 V) is applied for the cleaning of the electrode surface (glassy carbon). The linear response range was optimized between 9 and 45 mg L-1 for dipyrone and 6 and 30 mg L-1 for paracetamol. Linear regression of these two series of experiments leads to excellent correlation coefficients (R = 0.999) for both analytes and recoveries of around 100%. The proposed methodology allows an analytical frequency of 45 injections h-1 with a consumption of 1.5 mL of solution per minute. The relative standard deviation for 24 successive injections of solutions containing DI and PCT was calculated as 0.4% and 0.2%, respectively. The developed methodology was successfully used for the determination of dipyrone and paracetamol in pharmaceutical samples. Keywords: simultaneous determination, dipyrone, paracetamol, flow injection analysis (FIA), multiple pulse amperometric detection Introduction Dipyrone (DI), also known as metamizol, is a widely used analgesic and antipyretic with proven efficiency in pharmaceutical formulations.1 Despite being restricted in some countries, like the United States, DI is commercially available in Brazil, mainly due to its strong analgesic effect and a relative *e-mail: low cost.2 In some drugs, DI is presented in combination with paracetamol (PCT), which is also an analgesic and antipyretic drug widely used in formulations for pain relief or fever reducer without causing gastric problems, such as aspirin.3 The combination of both drugs is indicated in order to enhance the effect by pharmacodynamics interaction,4,5 which may justify the presence of DI and PCT in the same formulation. Due to the low cost of generic medicinal products Article Simple Flow Injection Amperometric System for Simultaneous Determination of Dipyrone and Paracetamol in Pharmaceutical Formulations 1250 Simple Flow Injection Amperometric System compared to brand-name medicinal products, the generic pharmacies can be an alternative way for acquisition of these medicines by consumer. However, there are some obstacles that hinder the growth of this field, and the most significant one is the lack of credibility in the generic drugs.6 On the other hand, the development of analytical methods that are simpler, faster and present lower costs, to incentive systems for a quality control of commerciallyavailable drugs, can promote the growth of this area. Efficient methodologies for the analysis of commercial drugs are also extremely important for quality control in the pharmaceutical field. Several works reported analytical methodologies for the determination of dipyrone or paracetamol. For dipyrone, procedures employing titration, 7,8 chromatography, 9,10 voltammetry,11 polarography,12 spectrophotometry,13,14 and flow methods using many detectors14-20 are described. For paracetamol, in the same manner, a considerable number of analytical methods are mentioned, as highlighted in a review recently published and other related works.3 However, few analytical methods are able to perform the simultaneous determination of DI and PCT, in cases where both compounds are concomitantly present in the sample. According to the US Pharmacopoeia (USP),21 when two or more active ingredients are present in a given formulation, the quantification must be carried out by high performance liquid chromatography (HPLC) with UV detection. Among the few references cited for simultaneous determination of DI and PCT, one of them mentions the use of titration,22 which requires prior stages of sample preparation and separation of the analytes, increasing significantly the time of analysis. Other methodologies applied HPLC-UV,9,23,24 based on official methods, which are expensive and usually require sample pretreatment, affecting the analytical frequency and producing significant quantities of organic solvents as waste. Thus, the development of procedures for faster and cheaper analyses, with selectivity and sensitivity comparable to the official methods, is a subject of great interest in this research area.25 Electroanalytical techniques are considered an alternative for the development of methods with reduced time and analysis costs, because they frequently enable the direct determination of electroactive compounds in complex samples.26 Among the electroanalytical methods, amperometric detection at constant potential coupled with FIA system provides good selectivity and high frequency for the analytical determination of many compounds.27,28 However, this method of detection is limited for cases in which the simultaneous determination of electroactive compounds at the same working electrode is required. Another limitation of amperometric detection at constant potential is related to the contamination of the electrode surface (...truncated)