Metabolism of drugs—LXII: Isolation and identification of morphine glucuronides in urine and bile of rabbits

Abstract

The isolation and identification of two morphine glucuronides in urine and bile of rabbits were studied. Charcoal adsorption and ion-exchange column chromatography with Dowex 50W-X8 and Dowex 1-X2 were effectively employed for the concentration and purification of the glucuronides. The major urinary metabolite was thus isolated in a crystalline form and was identified as morphine 3-glucuronide by comparison with a synthetic sample. It was also found by means of TLC that the same glucuronide was excreted in the bile as a major metabolite. Morphine 6-glucuronide could not be detected in either unfractionated urine or bile samples; however, after repeated purification of urinary extracts, this glucuronide was demonstrated for the first time to be a minor metabolite of morphine.