BIOCHEMICAL STUDIES ON CHLORAMPHENICOL (CHLOROMYCETIN*) III. ISOLATION AND IDENTIFICATION OF METABOLIC PRODUCTS IN URINEt

When chloramphenicol is administered by mouth to normal human subjects, only 5 to 10 per cent of the administered dose is excreted unchanged in the urine, as determined by microbiological assay methods (3, 4). However, with calorimetric methods for aromatic nitro compounds (5), from 75 to 90 per cent of the administered dose is accounted for in 24 hour urinary excretion in man (3). The major portion of these nitro compounds exhibits no antibiotic activity, and represents inactive degradation products of chloramphenicol. In lower animals, lesser amounts of nitro compounds are recovered in the urine, the remainder being excreted in the bile and feces, where considerable reduction occurs with the formation of aromatic amines (3). The present communication is concerned with the isolation and identification of chloramphenicol and its metabolic products from urine, chromatographic and counter-current methods for separation being used. The major excretory product in urine is shown to be a monoglucuronide derivative of chloramphenicol by enzymatic and chemical degradation studies.