Identification and quantitation of phenylethylene glycol in human and rat urine, and its elevation in phenylketonuria.

Phenylethylene glycol has been identified in rat and human urine using gas chromatography/chemical ionization/mass spectrometry. A method was developed for the quantitative analysis in urine of this phenylalanine metabolite and of p-hydroxyphenylethanol, a metabolite of tyrosine, by converting them to the pentafluoropropionyl derivatives and measuring them by selected ion monitoring. In human urine, about 90% of the phenylethylene glycol was present in a conjugated form (releasable by glusulase), but the reverse was true for rat urine, with about 90% being present in the unconjugated form. The excretion of free phenylethylene glycol (expressed as ng/mg creatinine) was 2.7-fold higher in a group of untreated phenylketonuric patients than in the control group, but the phenylketonuric patients excreted abnormally low amounts of 3-methoxy-4-hydroxyphenylethylene glycol. Intraperitoneal injections of L-phenylalanine in rats resulted in a small increase in the excretion of phenylethylene glycol. On the other hand, the injection of phenylethanolamine resulted in an 82-fold increase in the excretion of phenylethylene glycol, but phenylethylamine had no effect. These results indicate that the conversion of phenylethylamine to phenylethanolamine is the rate limiting step in this metabolic pathway.