title: Improvements in monitoring the N-terminal valine adduct in human globin after exposure to sulfur mustard and synthesis of reference chemicals.
abstract: The N-terminal valine adduct (HETE-Val) in globin is believed to behave as a long-lived biomarker after exposure to sulfur mustard (HD). Development of a highly sensitive method for monitoring HETE-Val, particularly at low HD exposure levels or for retrospective detection, would be a significant achievement. In this study, by improving the sample preparation method, a sensitive NCI-GC/MS method was established for the analysis of HETE-Val in globin after HD exposure. To optimize and investigate the sample preparation method, all the relevant HETE-Val chemicals were synthesized, purified, and characterized. By carrying out optimized solid phase extraction (SPE) cleanup followed by modified Edman degradation results in a low detection level and clean baseline. The minimum detectable exposure level of human blood (in vitro) to HD is 20 nmol/L (S/N>3). The interday and intraday precisions of the proposed method were found to be acceptable with less than a 15% relative standard deviation (RSD). A nearly linear dose-effect relationship was observed between HETE-Val and a HD exposure concentration range of 0.1-120 μmol/L. The percentage of HD that reacted with N-terminal valine in globin obtained from human blood (in vitro) was quantified using the proposed method.
authors: Beijing Institute of Pharmacology and Toxicology, No. 27 Tai Ping Road, Hai Dian District, Beijing 100850, PR China. niezhiyong2008@163.com
authors: Zhiyong
authors: Z
authors: Nie
authors: Qin
authors: Q
authors: Liu
authors: Jianwei
authors: J
authors: Xie
mesh_terms: D001774:Blood Chemical Analysis; D004781:Environmental Exposure / Q000032:analysis* / Q000592:standards; D008401:Gas Chromatography-Mass Spectrometry; D005914:Globins / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D057230:Limit of Detection; D016014:Linear Models; D009151:Mustard Gas / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D012015:Reference Standards; D052616:Solid Phase Extraction; D014633:Valine / Q000378:metabolism*; D005466:Fluorocarbons
chemical_list: D005914:Globins; D007093:Imidazoles; D009151:Mustard Gas; D014633:Valine; C046634:1-(heptafluorobutyryl)imidazole; D005466:Fluorocarbons