High performance liquid chromatography of a new 1,4-dihydropyridine: applications to pharmacokinetic study in dogs

A new nitrendipine derivative [ethyl-2-(1-piperidino)ethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)- 3,5-pyridine dicarboxylate hydrochloride;1] was assayed in plasma by high-performance liquid chromatography. After deproteinization and extraction, 1 and nitrendipine, as the external standard, were separated by ion-pair chromatography and measured by UV detection (254 nm). The method is rapid and specific: the limit of sensitivity of the assay was 5 ng/mL and the concentration range was linear between 5 and 2000 ng/mL. In vitro studies showed that, in contrast to nifedipine and nicardipine, 1 and nitrendipine were stable when exposed to light for at least 4 h. Pharmacokinetic parameters obtained in three beagle dogs after oral and intravenous administration are reported. Comparison with a nicardipine pharmacokinetic study showed similar results for the distribution and elimination characteristics of these two drugs.