Determination of alentamol hydrobromide, a novel antipsychotic agent, in human blood plasma and urine by high-performance liquid chromatography with fluorescence detection and solid-phase extraction.

Alentamol hydrobromide, (+)-2-(dipropylamino)-2,3-dihydro-1H-phenalen-5-ol monohydrobromide, is a selective dopamine agonist currently being investigated for the treatment of schizophrenia. This paper describes a reversed-phase high-performance liquid chromatographic-based method for the quantification of alentamol in blood plasma and urine. The method utilizes solid-phase extraction with carboxylic acid-derivatized silica columns. A limit of quantitation of 0.1 ng/ml in plasma was achieved by virtue of selective extraction and fluorescence detection. Example chromatograms of plasma and urine specimens from clinical trials demonstrate the utility of the method.

Quantitative liquid chromatographic determination of bromadoline and its N-demethylated metabolites in blood, plasma, serum, and urine samples.

Bromadoline and its two N-demethylated metabolites were extracted into ether:butyl chloride after the addition of internal standard and basification of the various biological fluids (blood, plasma, serum, and urine). These compounds were then extracted into dilute phosphoric acid from the organic phase and separated on a reversed-phase chromatographic system using a mobile phase containing acetonitrile and a buffer of 1,4-dimethylpiperazine and perchloric acid. The overall absolute extraction recoveries of these compounds were approximately 50-80%. The background interferences from the biological fluids were negligible and allowed quantitative determination of bromadoline and the metabolites at levels as low as 2-5 ng/mL. At mobile phase flow rate of 1 mL/min, the sample components and the internal standard were eluted at the retention times within approximately 7-12 min. The drug- and metabolite-to-internal standard peak height ratios showed excellent linear relationships with their corresponding concentrations. The analytical method showed satisfactory within- and between-run assay precision and accuracy, and has been utilized in the simultaneous determination of bromadoline and its two N-demethylated metabolites in biological fluids collected from humans and from dogs after administration of bromadoline maleate.