A systematic approach to the investigation of metabolic degradation of drugs is presented. Extraction of the biological sample is avoided by direct injection of bile or urine in a reversed-phase high-performance liquid chromatography system. Good separation of the various metabolites is obtained by changing the composition of the mobile phase so that all components become separated from the solvent front and are eluted from the column. The metabolites can be detected by measuring the amount of radioactivity in the column effluent, which also serves as a check on the overall recovery. Simultaneous registration of the UV absorbance permits certain conclusions to be drawn with regard to the nature of the metabolites. This approach is illustrated in the screening for metabolites of Butoprozine, a new anti-anginal drug, in rat bile. Essentially, all metabolites could be followed by suitable adaptations of the mobile phase, thus providing a metabolid profile with a recovery of 95% of the radioactivity.