硫芥与活性硫醇化合物加合特性的分析研究  

Investigation of Adductive Characteristics of Sulfur Mustards with Active Thiols

作　　者：张梦瑶 蔡金龙 龚梦强 徐斌 吴剑峰 吴海霞[1] 谢剑炜 ZHANG Meng-Yao;CAI Jin-Long;GONG Meng-Qiang;XU Bin;WU Jian-Feng;WU Hai-Xia;XIE Jian-Wei(College of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shjiazhuang 050091,China;Laboratory of Toxicology Analysis,Academy of Military Medical Sciences,Beijing 100850,China;Department of Environment and Life Science,Beijing University of Technology,Beijing 100124,China)

机构地区：[1]河北科技大学化学与制药工程学院,石家庄050091 [2]军事医学研究院国家安全特需药品全国重点实验室,北京100850 [3]北京工业大学环境与生命学部,北京100124

出　　处：《分析化学》2024年第7期995-1003,共9页Chinese Journal of Analytical Chemistry

摘　　要：硫芥是一类具有高反应活性的化学战剂,可造成多靶点损伤和糜烂,但其毒性及损伤机制至今尚未完全明确。本研究采用微量定向合成方法制备了8种芥子气类似物,并采用超高效液相色谱-高分辨质谱联用(UPLC-MS/HRMS)技术和高效液相色谱-三重四极杆质谱联用(HPLC-MS/MS)技术考察了其分别在孵育液、血浆和细胞等基质中,与谷胱甘肽(GSH)、半胱氨酸(Cys)和N-乙酰半胱氨酸(NAC)形成加合物的速率与丰度差异。结果表明,在孵育液中,硫芥均可与这3种硫醇分子发生加合反应;在血浆基质中,Cys与硫芥加合物的含量高于GSH与硫芥加合物的含量,而NAC与硫芥的加合物的种类较少,这可能是由于NAC的含量较低或质谱响应差所导致;在染毒细胞基质中,GSH与硫芥加合物的含量高于Cys与硫芥加合物的含量,其原因是这3种硫醇分子的自身反应活性以及血浆和细胞中硫醇分子含量均存在显著差异。An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

关 键 词：硫芥 加合物 谷胱甘肽 半胱氨酸 N-乙酰半胱氨酸 

分 类 号：TQ460.72[医药卫生—药物分析学] O657.63[化学工程—制药化工]