Accumulation of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in blood and organs of the Lewis rats.

Abstract

3-(Phenylamino)alanine (PAA), a newly discovered impurity in case-associated L-tryptophan tablets, has been investigated as a possible contributing factor in the etiology of eosinophilia-myalgia syndrome (EMS). We have studied distribution and elimination of PAA in rats which were administered a single 5 mg/kg dose of PAA by gastric gavage. PAA concentrations in blood, brain, kidney and liver were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. The concentration of PAA in each tissue reached a maximum at 5 h, and then gradually declined. A high level of PAA still remained at 24 h, indicating gradual elimination. The concentration of PAA in brain at 5 h was 2139 ng/g tissue, demonstrating passage through the blood-brain barrier. Consecutive administration of PAA (5 mg/kg) for 4 days resulted in approximately double the concentration in all tissues. Chronic treatment using PAA incorporated into food pellets for 6 weeks resulted in similar accumulations in each tissue, and following 12 days on a PAA free diet, levels of this drug were still detectable in all tissues.

• Authors: J Adachi, M Gomez, C C Smith, E M Sternberg
• Journal: Archives of toxicology (Arch Toxicol) Vol. 69 Issue 4 Pg. 266-70 ( 1995) ISSN: 0340-5761 [Print] Germany
• PMID: 7755488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(phenylamino)alanine
• Tryptophan
• Alanine

Topics

• Alanine (administration & dosage, analogs & derivatives, pharmacokinetics, toxicity)
• Animals
• Chromatography, High Pressure Liquid
• Drug Contamination
• Drug Residues
• Eosinophilia-Myalgia Syndrome (chemically induced)
• Female
• Rats
• Rats, Inbred Lew
• Tissue Distribution
• Tryptophan