Identification of the diketopiperazine of histidylproline in human urine.

During surveys of amines in the urine of children, Perry et al. (1) and Perry and Schroeder (2) found among the unidentified free bases present a substance which produced an orange-red color when chromatograms were sprayed with diazotized sulfanilic acid. This substance was designated “Compound 9.” Subsequently Compound 9 has been detected in all amine concentrates of unhydrolyzed urines of a large number of children and adults. More recently this substance was found to be present in greatly increased amounts in the urines of patients with phenylketonuria who were being fed a low phenylalanine diet. In this paper we present experiments which have led to the identification of Compound 9 as the diketopiperazine of histidylproline,