Comparison of Paracetamol-Induced Hepatotoxicity in the Rat in vivo with Progression of Cell Injury in Vitro in Rat Liver Slices

Um eletrodo modificado quimicamente foi construído, baseado em eletrodo de carbono vítreo modificado por nanotubos de carbono de parede múltipla (MWCNTs/GCE). Demonstrou-se que este sensor pode ser usado para a determinação simultânea de compostos com importância farmacêutica, como o paracetamol (PAR) e o tramadol (TRA). As medidas foram realizadas com aplicação de voltametria de pulso diferencial (DPV), voltametria cíclica (CV) e cronoamperometria (CA). A aplicação do método DPV demonstrou que em tampão fosfato (pH 7,5) há uma relação linear entre a corrente de pico de oxidação e a concentração de PAR no intervalo entre 0,5 μmol L -1 e 210 μmol L -1 . Uma correlação linear semelhante, entre a corrente de pico de oxidação e a concentração, foi observada para TRA no intervalo de 2 μmol L -1 a 300 μmol L -1 . Sob condições ótimas, o eletrodo modificado exibiu alta sensibilidade, seletividade e estabilidade para a determinação de ambos, PAR e TRA, tornando este, um sensor adequado para a detecção submicromolar simultânea de PAR e TRA, em soluções. O desempenho analítico deste sensor foi avaliado para detecção de PAR e TRA em soro e urina humanos e em algumas preparações farmacêuticas, com resultados satisfatórios.A chemically modified electrode was constructed based on a multi-walled carbon nanotubemodified glassy carbon electrode (MWCNTs/GCE). It was demonstrated that this sensor can be used for the simultaneous determination of the pharmaceutically important compounds paracetamol (PAR) and tramadol (TRA). The measurements were carried out by the application of differential pulse voltammetry (DPV), cyclic voltammetry (CV) and chronoamperometry (CA) methods. Application of the DPV method demonstrated that in phosphate buffer (pH 7.5) there was a linear relationship between the oxidation peak current and the concentration of PAR over the range 0.5 μmol L -1 to 210 μmol L -1. A similar linear correlation between oxidation peak current and concentration was observed for TRA over the range of 2 μmol L -1 to 300 μmol L -1. Under optimal conditions the modified electrode exhibited high sensitivity, selectivity and stability for both PAR and TRA determination, making it a suitable sensor for the simultaneous submicromolar detection of PAR and TRA in solutions. The analytical performance of this sensor has been evaluated for detection of PAR and TRA in human serum, human urine and some pharmaceutical preparations with satisfactory results.

Section: Effect Of Modification Of the Electrodes On The Effective Areamentioning

confidence: 89%

“…K 3 Fe(CN) 6 exhibited a pair of quite reversible redox peaks at a bare GC electrode. At the modified electrode, a pair of higher and reversible redox peaks could still be observed.…”

Section: Effect Of Modification Of the Electrodes On The Effective Areamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A multi-walled carbon nanotube-modified glassy carbon electrode as a new sensor for the sensitive simultaneous determination of paracetamol and tramadol in pharmaceutical preparations and biological fluids

Babaei¹,

Taheri²,

Afrasiabi³

2011

“…21 Overdose ingestions of acetaminophen lead to accumulation of toxic metabolites, which cause severe and sometimes fatal hepatotoxicity and nephrotoxicity. 22,23 This drug is available in different dosage forms of tablets, capsules, suspensions and suppositories and sometimes it is present along with other analgesic agents such as dypirone. For quantification of paracetamol in pharmaceutical products, the American Pharmacopoeia recommends liquid chromatography as the official method while the Brazilian Pharmacopoeia uses a spectrophotometric technique.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous voltammetric determination of dypirone and paracetamol with carbon paste electrode and multivariate calibration methodology

Skeika¹,

Faria²,

Nagata³

et al. 2008

Esse artigo descreve a determinação simultânea de dipirona (DIP) e de paracetamol (PAR) utilizando a técnica de Voltametria de Pulso Diferencial (VPD) e eletrodo de pasta de carbono não modificado. Devido à sobreposição dos picos voltamétricos de DIP e PAR, a metodologia de calibração multivariada baseada na Regressão de Mínimos Quadrados Parciais (PLSR) foi proposta. O conjunto de voltamogramas obtidos na presença de ambos os analitos em diferentes concentrações foi pré-processado pelos dados centrados na média. Para escolha do número de componentes principais, um procedimento de validação cruzada foi empregado, sendo que quatro componentes principais foram necessárias para obtenção dos menores valores de PRESS (Prediction Residual Error Sum of Squares). Esse modelo explicou aproximadamente 95,5% da variância do conjunto de dados. Os dados obtidos utilizando-se esse modelo mostraram uma alta correlação entre as concentrações reais e previstas. Entretanto, para baixas concentrações do PAR, os erros relativos aumentaram para 25%. Comparando-se os valores de RMSEP (Root Mean Square of Error Prediction), entre PAR e DIP, foi observado que este foi menor para DIP, provavelmente devido a maior quantidade de informação analítica apresentada pelos voltamogramas desse analito quando comparado ao processo redox de PAR, o qual devido a sua oxidação irreversível apresenta apenas um único pico. This paper shows the simultaneous electrochemical determination of dypirone (DIP) and paracetamol (PAR) by differential pulse voltammetry technique (DPV) using an unmodified carbon paste electrode. Because of the overlapping of the voltammetric peaks of DIP and PAR, the multivariate calibration methodology based on Partial Least Square Regression (PLSR) was proposed. The data pre-treatment used in this process was mean centering and to choose the principal component number a cross validation procedure was used (leave-one-out). Four principal components were necessary to obtain the lowest PRESS (Prediction Residual Error Sum of Squares). The statistics showed that this model explains approximately 95.5% of the variance from the data set. Using this model, high correlation between real and predicted concentrations was observed. However, for low concentrations of PAR the relative error increased to 25%. Comparing RMSEP (Root Mean Square of Error Prediction) between PAR and DIP, it was observed that it was lower for DIP probably due to higher analytical information in the voltammograms for this analyte when compared to the electrochemical process of PAR, which presented only one potential peak due to its irreversible oxidation.

“…1 Nevertheless, the ease with which ordinary people can access this drug makes it frequently associated with overdoses, in this situation causing serious or even fatal hepatic damage. 2 An overdose of ACT can lead to the accumulation of toxic metabolites, which may cause severe and some times fatal hepatoxicity and nephrotoxicity [3][4][5] and it can also cause liver disorders, skin rashes and inflammation of the pancreas. 6 The product of hydrolytic degradation of ACT is 4-aminophenol which can be found in pharmaceutical preparations as a degradation product of ACT or as a synthetic intermediate which can be dangerous and causes teratogenic effect and nephrotoxicity.…”

mentioning

confidence: 99%

A sensitive determination of acetaminophen in pharmaceutical preparations and biological samples using multi-walled carbon nanotube modified glassy carbon electrode

Babaei¹,

Afrasiabi²,

Mirzakhani³

et al. 2011

Um eletrodo quimicamente modificado foi construído, baseado em eletrodo de carbono vítreo modificado por nanotubos de carbono de paredes múltiplas (ECV-NTCPM). O uso deste sensor na determinação de acetaminofeno (ACT), em meio aquoso tamponado, foi demonstrado. As medidas foram realizadas com utilização dos métodos de voltametria de pulso diferencial (VPD), voltametria cíclica (VC) e cronoamperometria (CA). A aplicação de VPD mostrou dois intervalos dinâmicos lineares. O primeiro intervalo dinâmico linear foi de 0,1 a 22 μmol L -1 , com equação de calibração Ip(μA) = 1,2782c (mmol L -1 ) + 0,2431 (R 2 = 0,9984) e o segundo intervalo dinâmico linear foi entre 26 e 340 μmol L -1 com equação de calibração Ip(μA) = 0,7793c (mmol L -1 ) + 11,615 (R 2 = 0,9986). O limite de detecção de 0,029 μmol L -1 (S/N = 3) foi obtido. O eletrodo modificado mostrou respostas eletroquímicas com alta sensitividade, excelente seletividade e estabilidade para determinação de ACT em condições ótimas, o que o torna um sensor adequado para detecção submicromolar de ACT em soluções. O desempenho analítico deste sensor foi avaliado para detecção de ACT em soro humano, urina humana e em preparações farmacêuticas com resultados satisfatórios.A chemically modified electrode is constructed based on multi-walled carbon nanotube modified glassy carbon electrode (MWCNTs/GCE). It was demonstrated that this sensor could be easily used for determination of acetaminophen (ACT) in aqueous buffered media. The measurements were carried out by application of differential pulse voltammetry (DPV), cyclic voltammetry (CV) and chronoamperometry (CA) methods. Application of DPV method showed two linear dynamic ranges. The first linear dynamic range was from 0.1 to 22 μmol L -1 , with a calibration equation of Ip(μA) = 1.2782c (mmol L -1 ) + 0.2431 (R 2 = 0.9984) and the second linear dynamic range was between 26 to 340 μmol L -1 with a calibration equation of Ip(μA) = 0.7793c (mmol L -1 ) + 11.615 (R 2 = 0.9986). A detection limit of 0.029 μmol L -1 (S/N = 3) was obtained. The modified electrode showed electrochemical responses with high sensitivity, excellent selectivity and stability for ACT determination at optimal conditions, which makes it a suitable sensor for submicromolar detection of ACT in solutions. The analytical performance of this sensor has been evaluated for detection of ACT in human serum, human urine and a pharmaceutical preparation with satisfactory results.Keywords: acetaminophen, carbon nanotube, modified glassy carbon, electrochemical sensor IntroductionAcetaminophen (N-acetyl-p-aminophenol) (ACT), also known as paracetamol, is a drug with antipyretic and analgesic action, frequently used in therapy and which has low toxicity when used at the recommended doses. 1 Nevertheless, the ease with which ordinary people can access this drug makes it frequently associated with overdoses, in this situation causing serious or even fatal hepatic damage. 2 An overdose of ACT can lead to the accumulation of toxic metabolites, which may cause severe an...