DETERMINATION OF THE RIFAMYCIN-RELATED HYPOLIPIDEMIC DRUG CGP-43371 IN HUMAN FECES, PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

A simple, rapid and sensitive normal-phase high-performance liquid chr omatographic (HPLC) method was developed and validated for the determi nation of a novel hypolipidemic agent in human feces, plasma and urine . This experimental drug candidate is structurally related to rifamyci n. The compound and internal standard were isolated from biological ma trices by a one step liquid-liquid extraction. Separations were achiev ed on a mu Porasil silica gel column. Recovery and reproducibility ass essments indicated good accuracy and precision. The overall mean relat ive recoveries were 93.3% from feces (0.2-20 mu g/mg), 95.1% from plas ma (20-500 ng/ml) and 97.5% from urine (20-500 ng/ml), with coefficien ts of variation ranging from 0.7 to 10.0% for feces, 3.0 to 12.7% for plasma and 2.3 to 10.6% for urine. The limits of quantification were 0 .2 mu g/mg for feces and 20 ng/ml for plasma and urine. The method has sufficient sensitivity to support clinical trials, and was utilized t o measure concentrations of the compound in fecal, plasma and urine sa mples from healthy male volunteers who had received a single 800-mg or al dose.