title: Structural characterization of a case-implicated contaminant, "Peak X," in commercial preparations of 5-hydroxytryptophan.
abstract: OBJECTIVE
  To determine the chemical structure of a contaminant, X1, previously found in eosinophilia myalgia syndrome case-implicated 5-hydroxytryptophan (5-OHTrp), and also present in over-the-counter (OTC) commercially available 5-OHTrp.
  
  
  METHODS
  Case-implicated 5-OHTrp as well as 6 OTC samples were subjected to accurate mass HPLC-mass spectrometry and HPLC-electrochemical detection, and reacted with reduced glutathione. Peak X1 was subsequently subjected to HPLC-tandem mass spectrometry (MS/MS), as well as the resulting nucleophilic glutathione product. All these data were compared with analysis carried out under identical conditions on authentic 4,5-tryptophan-dione (Trp-4,5D).
  
  
  RESULTS
  Based on accurate mass, tandem mass spectrometric analysis, and comparision with authentic standard compound analysis, X1 was determined to be 4,5-tryptophan-dione, a putative neurotoxin. The presence of X1 in OTC samples varied from 0.5 to 10.3% of the amount of Trp-4,5D present in case-implicated 5-OHTrp.
  
  
  CONCLUSIONS
  Peak X1 was identified as the putative neurotoxin Trp-4,5D. It was found in case-implicated 5-OHTrp as well as 6 OTC samples. This gives some cause for concern in terms of the safety of such commercial preparations of 5-OHTrp.
authors.affiliation: Biomedical Mass Spectrometry and Functional Proteomics Facility, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Klarskov
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Johnson
authors.forename: Linda M
authors.initials: LM
authors.lastname: Benson
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Cragun
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: Monika
authors.initials: M
authors.lastname: Wrona
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Jiang
authors.forename: Glenn
authors.initials: G
authors.lastname: Dryhurst
authors.forename: Stephen
authors.initials: S
authors.lastname: Naylor
mesh_terms: D006916:5-Hydroxytryptophan / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced*; D006801:Humans; D013058:Mass Spectrometry
chemical_list: D006916:5-Hydroxytryptophan