Determination of ivabradine and its N-demethylated metabolite in human plasma and urine, and in rat and dog plasma by a validated high-performance liquid chromatographic method with fluorescence detection.

A sensitive and selective high-performance liquid chromatographic method with native detection of fluorescence was developed and validated for the quantitation of ivabradine and its N-demethylated metabolite in plasma (rat, dog, human) and human urine. The procedure involves the use of an analogue as internal standard, solid-phase extraction on cyano cartridges, separation on a Nova-Pak C8 column and fluorescence detection. Calibration curves are linear in the concentration ranges from 0.

Determination of S 12024 enantiomers in human plasma by liquid chromatography after chiral pre-column derivatization.

S 12024-2 is a new drug in phase II development that possesses cognitive enhancing properties. As its molecular structure has a chiral centre, a stereoselective method for the analysis of both enantiomers in human plasma has been developed. The method involves pre-column derivatization of the amine moiety with a homochiral reagent (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), and chromatographic separation of the two diastereoisomers on an achiral reversed-phase cyanopropyl column, with fluorimetric detection (lambda ex = 260 nm; lambda em = 310 nm).

First-pass metabolism of pentamethylmelamine in the rat liver.

The disposition of pentamethylmelamine (PMM) was studied in the male Wistar rat. PMM (5 mg/kg) was administered intraarterially, i.v.

The area under the curve of metabolites for drugs and metabolites cleared by the liver and extrahepatic organs. Its dependence on the administration route of precursor drug.

The venous equilibrium model (or well-stirred model) is used to determine the area under the blood concentration vs. time curve of a metabolite formed from a precursor drug. It will be shown that the AUC of a metabolite will change according to the route of precursor drug administration(whether intraarterially, intravenously, via the portal vein, or orally) when the drug and/or metabolite is eliminated by more than one organ.

Low oral bioavailability of hexamethylmelamine in the rat due to simultaneous hepatic and intestinal metabolism.

The disposition of both hexamethylmelamine (HMM) after intraarterial, i.v., portal vein, and intraduodenal administration and of pentamethylmelamine following its i.