RESUMEN
1H and 13C NMR spectra of cis- and trans-3-(2-[2-(4-methylphenyl)ethenyl]phenyl])sydnones, the first stilbene-substituted mezoionic oxadiazolium rings, were fully assigned combining the information in various solvents, such as deuterated benzene, acetone and chloroform, using 2D NMR techniques.
Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Sidnonas/química , Acetona/química , Benceno/química , Isótopos de Carbono , Cloroformo/química , Deuterio/química , Estructura Molecular , Oxadiazoles/química , Solventes , Estereoisomerismo , Estilbenos/química , Sidnonas/análisis , TritioRESUMEN
The pharmacokinetics and metabolism of synthetic 2-hydroxymesocarb and 4-methyl-2-hydroxymesocarb analyzed by HPLC-DAD and thermospray LC-MS were studied in rats. Multistep liquid-liquid extraction (LLE) was used with diethyl ether at pH 7.0. The major metabolites of 2-hydroxymesocarb in both urine and plasma of the rat were the p-hydroxylated derivative of the phenylcarbamoyl group of the parent drug. The metabolites of 4-methyl-2-hydroxymesocarb in urine of rats may be the oxidized forms at the phenylcarbamoyl group of the parent drug. Absorption (ka) and elimination (ke) rate constants in plasma of 2-hydroxy-mesocarb were 0.0300 and 0.00485 min-1, respectively; those of 4-methyl-2-hydroxymesocarb were 0.0546 and 0.00797 min-1, respectively. The half-lives (t1/2) of 2-hydroxymesocarb and 4-methyl-2-hydroxymesocarb in plasma were 144 and 86 min, respectively.
Asunto(s)
Estimulantes del Sistema Nervioso Central/análisis , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Sidnonas/análisis , Animales , Calibración , Estimulantes del Sistema Nervioso Central/sangre , Estimulantes del Sistema Nervioso Central/farmacocinética , Estimulantes del Sistema Nervioso Central/orina , Cromatografía de Gases y Espectrometría de Masas/métodos , Ratas , Sidnonas/sangre , Sidnonas/farmacocinética , Sidnonas/orinaRESUMEN
The title study permitted detecting genetic differences in sydnocarb metabolism. It was established that the rate of sydnocarb oxidation in BALB/c mice was higher than in C57B1/6 mice.
Asunto(s)
Ratones Endogámicos BALB C/metabolismo , Ratones Endogámicos C57BL/metabolismo , Oxadiazoles/metabolismo , Psicotrópicos/metabolismo , Sidnonas/metabolismo , Animales , Encéfalo/metabolismo , Radioisótopos de Carbono , Cromatografía/métodos , Cinética , Hígado/metabolismo , Masculino , Ratones , Unión Proteica/efectos de los fármacos , Psicotrópicos/análisis , Solubilidad , Especificidad de la Especie , Sidnonas/análisis , Factores de TiempoRESUMEN
A high-performance liquid chromatographic method is described for the analysis of the anti-anginal compound 5-ethoxycarbonyl-3-morpholinosydnonimine (Molsidomine) in human and dog plasma. The drug was extracted from plasma into chloroform and the analysis was carried out on a reversed-phase column, the column effluent being monitored by UV absorption at 312 nm. The method is sensitive (2 +/- 0.3 ng/ml) and specific. The method was applied to a study in which human volunteers received an aqueous solution of the drug and then, on a separate occasion, a tablet formulation. Peak plasma levels of 20--30 ng/ml (tablet) and 10--19 ng/ml (aqueous solution) were obtained following a 2-mg oral dose.