IDENTIFICATION OF DIPHENHYDRAMINE URINARY METABOLITES IN RHESUS MONKEY

The products of diphenhydramine metabolism which were found in the urine of rhesus monkeys included unchanged diphenhydramine, the primary and secondary amine analogs of diphenhydramine, diphenhydramine-N-oxide, a glucuronide of unknown structure, (diphenylmethoxy)acetic acid and the glutamine conjugate of this acid. As a part of indentification criteria, the glutamine conjugate of (diphenylmethoxy) acetic acid was synthesized and characterized. The conjugate was the major excretion product and together with (diphenylmethoxy)acetic acid accounted for nearly two-thirds of the urinary metabolites. Identification of this conjugate provides the first direct evidence that the rhesus monkey forms glutamine conjugates with carboxylic acids other than arylacetic acids. © 1968.