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.