Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.
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| Abstract |
3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6 micrograms between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.
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| Authors | J Adachi, T Mio, Y Ueno, T Naito, A Nishimura, S Fujiwara, K Sumino, Y Tatsuno |
| Journal | Archives of toxicology (Arch Toxicol) Vol. 68 Issue 8 Pg. 500-5 ( 1994) ISSN: 0340-5761 [Print] Germany |
| PMID | 7802590 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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