RESUMO
A sample of 0.104 M nicardipine in methanol was photoirradiated with a Philips 400 W UV lamp for 3 h in a photochemical chamber. A total of four major photoproducts were found from the HPLC chromatogram. The same sample was used for taking LC-MS, while eight major photoproducts were observed and the structures elucidated by analyzing the CID patterns of their respective mass spectra. A reaction scheme of nicardipine is proposed that the photochemical reactions occur mainly via oxidation of 1,4-dihydropyridine moiety, following the stepwise photo-reduction of the m-nitro group and demethylation of the ester group at 5-position of the pyridine ring.
Assuntos
Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Nicardipino/química , Nicardipino/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray/métodos , Nicardipino/análogos & derivados , FotoquímicaRESUMO
A capillary gas chromatographic method with nitrogen-phosphorus detection for the simultaneous determination of nicardipine and its pyridine metabolite M-5 was developed. The method involves extraction of the plasma with hexane-methylene chloride (1:1, v/v), followed by evaporation of the organic phase. The extract is injected into a fused-silica capillary column coated with cross-linked 5% phenyl-methylsilicone. A temperature gradient (85-285 degrees C) is applied and the two products and the internal standard can be separated within 22 min. The limit of detection is 0.5 ng/ml for both products. The method is suitable for pharmacokinetic studies in humans.
Assuntos
Cromatografia Gasosa/métodos , Nicardipino/análogos & derivados , Nicardipino/metabolismo , Nitrogênio/análise , Fósforo/análise , Calibragem , Humanos , Nicardipino/sangueRESUMO
A rapid, specific and direct method based on capillary column gas chromatography with electron-capture detection is described for the simultaneous determination of nicardipine, a new calcium antagonist, and its pyridine metabolite II in human plasma. In this method, the nicardipine, its pyridine metabolite II and internal standard are extracted from the plasma and then partially purified by acid-base partitioning prior to the final injection onto the capillary column gas chromatograph for quantification by means of an electron-capture detector. The quantification limit of the method is 1 ng/ml of plasma for both nicardipine and its pyridine metabolite II. The coefficients of variation for nicardipine and the pyridine metabolite II at concentrations of 1-50 ng/ml are less than 7% and less than 9% (n = 4), respectively. The method has been validated against a previously developed high-performance liquid chromatographic method (sensitivity 5 ng/ml).
