The metabolism of ingested deuterium-labelled p-tyramine in normal subjects

Eight normal subjects ingested 125 mg of p-tyramine-beta,beta-2H2 hydrochloride and the 3 h and following 21 h urine collections were analysed by mass spectrometry with selected ion monitoring for the deuterated metabolites: free and conjugated p-tyramine-beta,beta-2H2, free p-octopamine-beta-2H1, free and conjugated p-hydroxyphenylacetic acid-alpha-2H1 and -alpha,alpha-2H2, and free p-hydroxymandelic acid-alpha-2H1. These metabolites accounted for 72% of the ingested label, of which conjugated p-tyramine and free p-hydroxyphenylacetic acid constituted 90%. Approximately 50% of the total deuterated tyramine and 70% of the total deuterated p-hydroxyphenylacetic acid were excreted in the first three hours, although there was considerable variation between individuals. The presence of a small amount of p-hydroxyphenylacetic acid-alpha-2H1 suggests that some exchange of deuterium occurred at the intermediate p-hydroxyphenylacetaldehyde stage. These results, based as they are on metabolites labelled with the stable isotope deuterium, ought to be more reliable than earlier studies in which unlabelled tyramine was ingested with the resultant metabolites, indistinguishable from their endogenous metabolic counterparts, being measured by fluorimetry or gas chromatography.