title: On-line HPLC-tandem mass spectrometry analysis of contaminants of L-tryptophan associated with the onset of the eosinophilia-myalgia syndrome.
abstract: The structural characterization of a number of contaminants of L-tryptophan (Trp) associated with eosinophilia myalgia syndrome has been performed for the first time by the powerful structural elucidation technique of tandem mass spectrometry coupled with on-line HPLC (LC-ESI-MS/MS). The identity of the contaminants: peaks UV-5, 3-(phenylamino)alanine, (PAA); E 1,1'-ethylidenebis(tryptophan); 200, 2-(3-indolylmethyl)-L-tryptophan; (all identified as case related) and peaks 1, 3-carboxy-1,2,3,4-tetrahydro-beta-carboline; 2, 3-carboxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline; 100, 2-(2,3 dihydroxy-1-[3-indolyl]propyl)-L-tryptophan; and 300 and 400, diastereomers of 3-carboxy-1-[3-indolyl-methyl]-1,2,3,4-tetrahydro-beta-carboline, have been confirmed by this technique. By comparison of tandem MS (MS/MS) data from these compounds with the MS/MS data of several other impurities, we have structurally characterized peaks CC, KK and OO, as well as two previously unreported components labeled as peak P18 and peak P31. Peak P18 was unresolved from the large Trp peak and has been characterized as indole-3-ethylamine. Peak P31 was previously unresolved from peak 200, a case related compound and therefore its structure is of extreme importance. This compound has been tentatively identified as 2-(3-indolyl)-L-tryptophan.
authors.affiliation: Biomedical Mass Spectrometry Facility, Department of Biochemistry and Molecular Biology, Mayo Clinic/Mayo Foundation, Rochester, Minnesota 55905, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Williamson
authors.forename: L M
authors.initials: LM
authors.lastname: Benson
authors.forename: A J
authors.initials: AJ
authors.lastname: Tomlinson
authors.forename: A N
authors.initials: AN
authors.lastname: Mayeno
authors.forename: G J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: S
authors.initials: S
authors.lastname: Naylor
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D014364:Tryptophan / Q000009:adverse effects / Q000032:analysis*
chemical_list: D014364:Tryptophan