Alkylation of Human Serum Albumin by Sulfur Mustard in Vitro and in Vivo: Mass Spectrometric Analysis of a Cysteine Adduct as a Sensitive Biomarker of Exposure

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• 作者：Daan Noort ; Albert G. Hulst ; Leo P. A. de Jong ; and Hendrik P. Benschop
• 刊名：Chemical Research in Toxicology
• 出版年：1999
• 出版时间：August 1999
• 年：1999
• 卷：12
• 期：8
• 页码：715 - 721
• 全文大小：91K
• 年卷期：v.12,no.8(August 1999)
• ISSN：1520-5010

文摘

To develop a mass spectrometric assay for the detection of sulfur mustard adducts withhuman serum albumin, the following steps were performed: quantitation of the binding ofthe agent to the protein by using [¹⁴C]sulfur mustard and analysis of acidic and tryptic digestsof albumin from blood after exposure to sulfur mustard for identification of alkylation sites inthe protein. The T5 fragment containing an alkylated cysteine could be detected in the trypticdigest with micro-LC/tandem MS analysis. Attempts to decrease the detection limit for in vitroexposure of human blood by analysis of the alkylated T5 fragment were not successful. AfterPronase treatment of albumin, S-[2-[(hydroxyethyl)thio]ethyl]Cys-Pro-Phe was analyzed bymeans of micro-LC/tandem MS, allowing a detection limit for in vitro exposure of human bloodof 10 nM, which is 1 order of magnitude lower than that obtained by means of modified Edmandegradation. The analytical procedure could be successfully applied to the analysis of albuminsamples from Iranian victims of the Iran-Iraq war.