Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome. (5th January 2018)

• Record Type: Journal Article
• Authors: Klarskov, Klaus; Gagnon, Hugo; Boudreault, Pierre-Luc; Normandin, Chad; Plancq, Baptiste; Marsault, Eric; Gleich, Gerald J.; Naylor, Stephen
• Is Part Of: Toxicology letters. Volume 282(2018)
• Page Start: 71
• Page End: 80
• Publication Date: 2018-01-05
• Subjects: CDC USACenters for Disease Control and Prevention -- CE collision energy -- CES collision energy spread -- DoU degree(s) of unsaturation -- ESI electrospray ionization -- EMS eosinophilia myalgia syndrome -- FDA USA Food and Drug Administration -- HPLC high performance liquid chromatography -- IDA information-dependent acquisition -- LC–MS microcapillary HPLC-mass spectrometry -- LC-UV HPLC with UV detection -- L-Trp l-Tryptophan -- NMR nuclear magnetic resonance -- MS/MS tandem mass spectrometry -- MSn multistage tandem mass spectrometry -- PAA 3-(phenylamino)alanine -- SD Showa Denko K.K -- TOF time-of-flight; Eosinophilia myalgia syndrome -- Peak AAA -- Case-associated -- Dietary supplements -- Contaminants; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.10.012
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: The final EMS case-associated contaminant, Peak AAA ofl -Tryptophan identified. Peak AAA shown to be two different structural isomers. Identified as two condensation products of L-Tryptophan with isomeric fatty acids. They possess very different properties from other 5 case associated contaminants. Abstract: The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion ofl -Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p = 0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC–MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers. Peak AAA1 and Peak AAA2 differed in LC retention times, and were determined by accurate mass-LC–MS to both have a protonated molecular ion (MH +) of mass 343.239 Da (Da), corresponding to a molecular formula of C21 H30 N2 O2, and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC–MS and LC–MS-MS retention times and spectra with authentic synthetic standards, Peak AAA1 was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford ( S )-2-amino-3-(2-((S, E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA2 was determined to be a condensation product of L-Trp with decanoic acid, which produced ( S )-2-amino-3-(2-(( E )-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid.