IDENTIFICATION OF 4 METABOLITES OF 3-(PHENYLAMINO)ALANINE, A CONSTITUENT IN L-TRYPTOPHAN PRODUCTS IMPLICATED IN EOSINOPHILIA-MYALGIA-SYNDROME, IN RATS

3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tabl ets, has been discussed as a possible cause of eosinophilia-myalgia sy ndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wis tar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by hig h performance liquid chromatography (HPLC) in order to determine level s of PAA. The level of PAA in blood was 4.22 mu g/ml at 5 h and urinar y excretion was 21.7 mu g for 5 h and 84.6 mu g between 5 and 24 h. Th e amount of PAA in the contents of the large intestine at 5 h was 0.76 mu g, indicating poor transfer of PAA to the large intestine. However , the highest concentration of PAA was 12.3 mu g/g in the brain, indic ating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabo lites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phe nylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)lacti c acid in rat urine. These results suggest that the degradation pathwa y of PAA is similar to that of phenylalanine.