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 bean developed to quantify novel arylene bi s(methylketone) chemotherapeutics present in biological samples. The s amples are extracted over cyanopropylsilane solid-phase extraction car tridges using 10 mM heptanesulfonate-10 mM tetramethylammonium chlorid e-4.2 mM H3PO4-95% CH3CN as the eluent, Analytical chromatography util ises a diisopropyl-C-8 reversed-phase column and a 7.5-45% CH3CN gradi ent in 10 mM heptanesulfonate-10 mM tetramethylammonium chloride-4.2 m M H3PO4-H2O. Detection was by ultraviolet spectrophotometry at 300 or 240 nm. The linear response of the assay was found to extend from at l east 100 mu g/ml down to 97.66 ng/ml for a 100 mu l injection. The ass ay system was utilised to determine the plasma kinetics of the compoun ds in mice, where all the drugs were found to display rapid absorption and elimination following intraperitoneal dosing. In vitro and in viv o studies of metabolism demonstrated that each of the compounds produc ed several metabolites, and that this conversion could be extensive in vivo.