LIQUID-CHROMATOGRAPHIC DETERMINATION OF THE POTENTIAL MEMORY ENHANCING AGENT CL-275,838 USING A POSTCOLUMN PHOTOLYSIS AND FLUOROMETRIC DETECTION

A method has been developed for quantitation of the potential memory-enhancing agent CL 275,838 (I) in plasma. After isolation of the compound I and the internal standard from plasma constituents using a Sep-Pak C18 cartridge and separation by reverse-phase liquid chromatography, the eluate peaks were passed through a PTFE photolysis coil irradiated by an UV lamp, resulting in conversion of the compounds to highly fluorescent species. The method was sensitive, precise and easily applicable for the automatic injection of series of plasma samples from healthy males in preliminary clinical studies of the oral compound I (10-100 mg). Absorption of I was rapid and peak plasma concentrations and area under the curve increased with the dose, suggesting that the pharmacokinetics of I are linear in the dose range investigated.