ONLINE FULLY AUTOMATED SOLID-PHASE EXTRACTION LIQUID-CHROMATOGRAPHY ANALYSIS OF IDYL)-2,2-DIMETHYL-1-OXONAPHTHALENE-6-CARBONITRILE (UR-8225), A NEW POTASSIUM CHANNEL OPENER, IN PLASMA SAMPLES

A fully automated reversed-phase HPLC method for pharmacokinetic studi es was developed for the determination in plasma samples of ro-4-(1,2- dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1- oxonaphthalene-6-carbonitrile (compound I), a new potassium channel opener. On-line solid-phase ext raction was performed with disposable C-18 cartridges. After clean up, the samples were eluted and transferred onto an RP-18 analytical colu mn, where separation was performed with a mobile phase of acetonitrile -10 mM di-n-butylamine phosphate (28:72, v/v). Ultraviolet absorbance detection was used at 236 nm. The detector response was linear in the range 25-2500 ng/ml, and the lowest limit of quantitation was determin ed at 2.5 ng/ml. The inter-day variability was <4% for samples at 1000 ng/ml and <15% for samples at 10 ng/ml. This method was used for the pharmacokinetic study of compound I in rats at three different dosage levels.