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Structural Characterization of a Case-Implicated Contaminant, "Peak X," in Commercial Preparations of 5-Hydroxytryptophan
KLAUS KLARSKOV, KENNETH L. JOHNSON, LINDA M. BENSON, JENNIFER D. CRAGUN, GERALD J. GLEICH, MONIKA WRONA, XIANG-RONG JIANG, GLENN DRYHURST, and STEPHEN NAYLOR
ABSTRACT.
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. Conclusion. 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. (J Rheumatol 2003;30:89-95) Key Indexing Terms:
EOSINOPHILIA MYALGIA SYNDROME
From the Biomedical Mass Spectrometry and Functional Proteomics Facility and Department of Biochemistry and Molecular Biology, the Allergy Research Unit, the Departments of Immunology and Medicine, the Department of Molecular Pharmacology and Experimental Therapeutics, Clinical Pharmacology Unit, and the Division of Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and the Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA. Supported by National Institutes of Health (AI31155), Showa Denko K.K., and the Mayo Foundation. K. Klarskov, PhD (currently Mass Spectrometry Laboratory, Department of Pharmacology, University of Sherbrooke, Sherbrooke, PQ, Canada); K.L. Johnson, MS; L.M. Benson, BS; J.D. Cragun, BS, Biomedical Mass Spectrometry and Functional Proteomics Facility and Department of Biochemistry and Molecular Biology, Mayo Clinic; G.J. Gleich, MD, Allergy Research Unit, Departments of Immunology and Medicine, Mayo Clinic; M. Wrona, PhD; X-R. Jiang, PhD; G. Dryhurst, PhD, Department of Chemistry and Biochemistry, University of Oklahoma; S. Naylor, PhD, Biomedical Mass Spectrometry and Functional Proteomics Facility, Department of Biochemistry and Molecular Biology, Department of Molecular Pharmacology and Experimental Therapeutics, Clinical Pharmacology Unit, Division of Biomedical Engineering, Mayo Clinic. Address reprint requests to Dr. S. Naylor, Beyond Genomics Inc., 40 Bear Hill Road, Waltham, MA 02451, USA. E-mail: SNaylor@BeyondGenomics.com Submitted March 12, 2002; revision accepted June 10, 2002.
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