Paracetamol, caffeine and ibuprofen are found in over-the-counter pharmaceutical formulations. In this work, we propose two new methods for simultaneous determination of paracetamol, caffeine and ibuprofen in pharmaceutical formulations. One method is based on high-performance liquid chromatography with diode-array detection and the other on capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation by high-performance liquid chromatography with diode-array detection was achieved on a C18 column (250×4.6 mm(2), 5 μm) with a gradient mobile phase comprising 20-100% acetonitrile in 40 mmol L(-1) phosphate buffer pH 7.0. The separation by capillary electrophoresis with capacitively coupled contactless conductivity detection was achieved on a fused-silica capillary (40 cm length, 50 μm i.d.) using 10 mmol L(-1) 3,4-dimethoxycinnamate and 10 mmol L(-1) β-alanine with pH adjustment to 10.4 with lithium hydroxide as background electrolyte. The determination of all three pharmaceuticals was carried out in 9.6 min by liquid chromatography and in 2.2 min by capillary electrophoresis. Detection limits for caffeine, paracetamol and ibuprofen were 4.4, 0.7, and 3.4 μmol L(-1) by liquid chromatography and 39, 32, and 49 μmol L(-1) by capillary electrophoresis, respectively. Recovery values for spiked samples were between 92-107% for both proposed methods.

1IntroductionThem ost used methods for the determination of drugsi n pharmaceutical samples are basedo nh igh performance liquid chromatography (HPLC) using an UV detector. Despite of these methods being highly robust, in general they present some drawbacks such as high generation of waste and low analyticalf requencyf or routine analysis. Thee lectroanalytical techniques have shown to be an attractive alternativeness for the determination of drugs in pharmaceutical formulations.T he electroanalytical methods present high selectivity because most of active components in formulations are electroactive species while the excipients do not present any faradaic response.F urthermore,t he electrochemical detection providesh igh sensitivity,l ow-cost and fast analysis with less waste generation. Ar ecentr eview of Uslu and Ozkan has listed more than 200 pharmaceutical compounds that were determined by electrochemical detection [1].A notheri mportanta dvantage of electroanalytical methodsi st he possibility of simultaneous determinations of two or more associateda ctive ingredients in pharmaceutical formulations.T here are manys tudies reported in the literature using electrochemical techniques for simultaneous determinations by voltammetric detection on various types of workinge lectrodes [2][3][4][5][6][7][8].When electroanalytical methodsa re coupled to flow injection analysis (FIA), therea re even more advantages for the determination of electroactivec ompounds in comparison with voltammetric techniques using stationary detection mode.T he methods developed by FIA with electrochemical detection are faster and the passage of solution on the working electroder educes its surface fouling (or contamination) and increases the reproducibility of analyses.H owever, there are few studies in the literature using FIA systems with electrochemical detectionf or simultaneous determinations of drugs because the conventional amperometric detection mode (application of aconstant potential) is not selective.I nr ecenty ears,t he multiAbstract:T his work presents as imple,f ast and low-cost methodf or the simultaneous determination of three drugs by flow-injection analysis with multiple-pulse amperometric (MPA) detectionu sing aw all-jet flow cell with ab oron-doped diamond electrode.T he amperometric determination of caffeine (CF), ibuprofen (IB) and paracetamol (PC)w as performed by the application of af our-potential waveform using the MPAt echnique. PC is oxidized at E 1 (1.20 V/70 ms) and thus selectively detected;P Ca nd CF are oxidizeda tE 2 (1.49 V/40 ms);P C, CF and IB are oxidized at E 3 (1.70 V/70 ms);a nd E 4 (1.80 V/100 ms) is appliedf or electrode cleaning. The subtraction of currents obtaineda tt he differentp otentials did not provide accurated eterminations of CF and IB,t hus it was required to investigate correction factors to determine CF and IB without the interference from PC and CF usingt he respectivea mperometric signals obtained at E 2 and E 3 .T he proposed method was successfully appliedf or the determinatio...

Recebido em 25/4/13; aceito em 17/5/13; publicado na web em 1/7/13 DETERMINATION OF NIMESULIDE BY FLOW INJECTION ANALYSIS WITH MULTIPLE-PULSE AMPEROMETRIC DETECTION. A simple and fast method for the determination of nimesulide (NI) using flow injection analysis with multiple-pulse amperometric (FIA-MPA) detection at a boron-doped diamond (BDD) electrode was developed. The method was based mainly on the application of a four-potential waveform, E 1(det) = -0.8 V / 30 ms, E 2(det) = 0.6 V / 30 ms, E 3(det) = -0.4 V / 30 ms and E 4(cleaning) = -0.45 V / 300 ms versus Ag/AgCl (3.0 mol L -1 KCl). NI was detected at three different electrode potentials, at which the nitro group undergoes different redox reactions. The proposed method was selective and sensitive (detection limit of 81.0 nmol L -1 ), and successfully applied for the determination of NI in pharmaceutical formulations, yielding similar results to those obtained by the reference method.Keywords: pulse amperometric detection; nimesulide; boron-doped diamond. INTRODUÇÃOA Nimesulida (NI), N-(4-nitro-2-fenoxifenil)metanossulfonamida, é um anti-inflamatório não-esteroide de alta atividade analgé-sica e antipirética, sendo amplamente prescrita e recomendada por apresentar melhor eficácia sobre os medicamentos similares, como ibuprofeno, diclofenaco e piroxicam.1 Além disso, a NI possui menor acidez (pKa = 6,9) e, consequentemente, melhor tolerabilidade gástrica quando comparada aos fármacos utilizados para a mesma finalidade, como o ácido acetilsalicílico (pKa = 3,4).2 Devido às vantagens apresentadas pela NI, este composto está entre os dez medicamentos mais vendidos no Brasil nos últimos anos.3 Neste contexto, este analito pode também ser classificado como um poluente orgânico emergente em amostras ambientais, como seus similares supracitados.4 Dessa forma, torna-se fundamental o desenvolvimento de métodos analíticos rápidos, simples e de baixo custo que possam ser utilizados no controle de qualidade deste fármaco em formulações farmacêuticas, bem como sua quantificação sensível e seletiva em amostras ambientais.A Farmacopeia Brasileira indica o doseamento da NI por dois métodos: espectrofotometria de absorção no UV-Vis e cromatografia líquida de alta eficiência (CLAE), ambos com detecção na região do ultravioleta.5 Os métodos espectrofotométricos acoplados (ou não) aos sistemas cromatográficos fazem parte da maioria dos métodos citados na literatura para a determinação de NI, tanto em formulações farmacêuticas como em amostras biológicas, conforme relatado em revisão publicada recentemente. 6 No entanto, grande parte dessas metodologias são de alto custo, requerem etapas complexas de pré--tratamento das amostras e geram resíduos provenientes da utilização de solventes orgânicos no procedimento analítico.Os métodos eletroanalíticos apresentam características interessantes para serem explorados na determinação de uma diversidade de compostos em formulações farmacêuticas e amostras de composição química mais complexa, como fluidos biológicos e amostras ambientai...