RESUMEN
A liquid chromatography-electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous quantitation of nicorandil and its denitrated metabolite, N-(2-hydroxyethyl)-nicotinamide, in rat plasma. After a liquid-liquid extraction step, chromatographic separation was performed on a ShinPack C(18) column with an isocratic mobile phase composed of methanol and 2 mM aqueous ammonium acetate containing 0.03% (v/v) formic acid (33:67 v/v). Procainamide was used as an internal standard (IS). Selected reaction monitoring was performed using the transitions m/z 212 â m/z 135, m/z 166 â m/z 106 and m/z 236 â m/z 163 to quantify nicorandil, its denitrated metabolite and IS, respectively. Calibration curves were constructed over the range of 5-15,000 ng.ml(-1) for both nicorandil and its metabolite. The mean relative standard deviation (RSD%) values for the intra-run precision were 5.4% and 7.3% and for the inter-run precision were 8.5% and 7.3% for nicorandil and its metabolite, respectively. The mean accuracy values were 100% and 95% for nicorandil and its metabolite, respectively. No matrix effect was detected in the samples. The validated method was successfully applied to a pharmacokinetic study after per os administration of nicorandil in rats.
Asunto(s)
Cromatografía Liquida/métodos , Niacinamida/análogos & derivados , Nicorandil/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Animales , Femenino , Masculino , Niacinamida/sangre , Niacinamida/farmacocinética , Nicorandil/farmacocinética , Procainamida/sangre , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
O objetivo da experiencia foi determinar o efeito da hiperlipidemia experimental na farmacocinetica da procainamida (PA) e N-acetilprocainamida (NAPA), cujo nome oficial e acecainida. A experiencia foi realizada em um periodo de dois meses em 20 coelhos, machos, divididos aleatoriamente em dois grupos: controle e experimental (deixado em dieta rica em gorduras). Depois dos dois meses foram realizadas determinacoes farmacocineticas em todos os animais. Apos administracao estomacal (por sonda) de procainamida em dose de 40 mg/kg, foi coletado sangue para as determinacoes, durante um periodo de 12 horas. Para calculos, foi tomado o modelo de dois compartimentos para administracao extravascular. Foi observada diminuicao da concentracao da PA e NAPA no sangue, diminuicao do volume de distribuicao e aumento da depuracao total. A presente experiencia demonstrou o efeito da hiperlipidemia experimental na farmacocinetica de PA e NAPA, seguido de aumento da velocidade de eliminacao do farmaco do organismo