Studies on the pharmacological properties of novel arylene bis(methylketone) compounds using solid-phase extraction and high-performance liquid chromatography

A method utilising solid-phase extraction followed by high-performance liquid chromatography has been developed to quantify novel arylene bis(methylketone) chemotherapeutics present in biological samples. The samples are extracted over cyanopropylsilane solid-phase extraction cartridges using 10 mM heptanesulfonate-10 mM tetramethylammonium chloride-4.2 mM H₃PO₄-95% CH₃CN as the eluent. Analytical chromatography utilises a diisopropyl-C₈ reversed-phase column and a 7.5–45% CH₃CN gradient in 10 mM heptanesulfonate-10 mM tetramethylammonium chloride-4.2 mM H₃PO₄-H₂O. Detection was by ultraviolet spectrophotometry at 300 or 240 nm. The linear response of the assay was found to extend from at least 100 μg/ml down to 97.66 ng/ml for a 100 μl injection. The assay system was utilised to determine the plasma kinetics of the compounds in mice, where all the drugs were found to display rapid absorption and elimination following intraperitoneal dosing. In vitro and in vivo studies of metabolism demonstrated that each of the compounds produced several metabolites, and that this conversion could be extensive in vivo.