Liquid chromatographic determination of oxcarbazepine and its metabolites in plasma of epileptic patients after solid-phase extraction.

A method based on high-performance liquid chromatography with UV detection in combination with solid-phase extraction for sample pretreatment has been developed for the simultaneous analysis of the antiepileptic drug oxcarbazepine and its main metabolites in human plasma. The extraction of the analytes from plasma samples was carried out by means of a selective solid-phase extraction procedure using hydrophilic-lipophilic balance cartridges. The separation was obtained on a reversed-phase column (C(18), 150x4.6 mm I.D., 5 micrometer) using a phosphate buffer-acetonitrile-methanol-triethylamine mixture (final apparent pH* 3.5) as the mobile phase. Under these chromatographic conditions, oxcarbazepine and its metabolites 10,11-dihydro-10-hydroxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine and the internal standard are baseline separated in less than 9 min. The extraction yield values were >94% for all analytes and the precision, expressed by the RSD%, was in the low percentage range. For the entire method, including sample pre-treatment and HPLC determination, the linearity of the calibration lines, expressed by the linear correlation coefficient, was better than 0.995; the limit of quantitation was 15 ng ml(-1). The method was applied to plasma samples from patients undergoing chronic treatment with oxcarbazepine, both in monotherapy and in polytherapy. Based on the analytical parameters precision, accuracy, limit of quantitation and analysis time the method is suitable for routine application in therapeutic drug monitoring.

Nonsteroidal antiinflammatory agents. XVIII - Stereomeric optically active halogenophenyl-biphenylyl-hydroxypropionic acids.

The optically active stereomers of some 3-(fluoro-, chloro-, bromophenyl)-2-biphenylyl-3-hydroxypropionic acids were prepared and tested for antiinflammatory activity. Surprisingly, the four bromo-isomers were the most active ones, particularly in the threo configuration.

Nonsteroidal anti-inflammatory agents. Part 17: Stereomeric o-, m-tolyl- and anisyl-biphenylyl-hydroxypropionic acids.

As a part of wider research project on chiral anti-inflammatory arylacanoic acids, the 3-(o- and m-)-(methyl and methoxy)-phenyl-2-biphenylyl-3-hydroxypropionic acids 3a-d were synthesized and resolved in their optically active erythro and threo stereomers, which were submitted to the carrageenan induced rat paw edema test. With respect to the p-isomers, only the threo p-methoxy substitution enhances the anti-inflammatory activity. Some conclusions on structure-activity relationship are discussed.

Nonsteroidal antiinflammatory agents. Part 16: Stereomeric 3-aryl-biphenylyl-hydroxy-propionic acids.

As part of a wider research project on structure-activity relationships of chiral arylalkanoic acids, stereomeric aryl- biphenylyl-hydroxypropionic acids 3a-d have been prepared and their antiinflammatory activity evaluated. Diastereomeric racemic erythro- and threo-acids have been synthesized by reaction of alpha-lithiated biphenylyl-acetic acid salts with the appropriate aldehyde. They were separated, and after attribution of their relative configuration by 1H-NMR analysis, resolved. The antiinflammatory activities of the enantiomeric potassium salts were determined by the carrageenan test.

On the antimicrobial activity of some new poly[2,6-bis(methyleneaminomethyl)-4-methyl]phenols and their N-iodoethylated salts.

The in vitro antimicrobial activity of the title polymers is described. Iodoethylation leads to a sensible improvement of activity only when the amino groups present in the main backbone of the polymers are connected by a long aliphatic chain.