马兜铃酸-脱氧鸟苷酸加合物的合成及质谱分析  

Synthesis and mass spectrometric analysis of aristolochic acid-deoxyguanosine adducts

作　　者：季文萱[1] 刘密新[2] 杨成对[2] 谌贻璞[1] 

机构地区：[1]中日友好医院,北京100029 [2]清华大学分析测试中心,北京100084

出　　处：《药学学报》2008年第3期295-298,共4页Acta Pharmaceutica Sinica

基　　金：卫生部属(管)医疗机构临床学科重点项目(2005-2007年度)

摘　　要：体外合成并应用多种质谱技术鉴定了马兜铃酸(aristolochic acid,AA)-脱氧鸟苷酸(2′-deoxyguanosine5′-monophosphate,dGp)加合物。AA经酶活化或化学活化后与dGp反应,同时优化反应条件。应用液相色谱-串联质谱(LC-MS/MS)以及傅里叶变换离子回旋共振质谱(FT-ICRMS)精确质量数测定和同位素模式等检测技术对合成样品进行分析。在样品中分别检测到AA-dGp加合物准分子离子峰,子离子谱图提供了加合物结构信息。AA能在体外与dGp形成AA-dGp加合物,质谱分析方法可以快速、方便、准确分析与鉴定AA-dGp加合物。To synthesize aristolochic acid （AA）-2＇-deoxyguanosine 5＇-monophosphate （dGp） adducts in vitro and develop a novel method for the characterization of the adducts using multiple mass spectrometric techniques. AA was incubated with dGp in vitro using either enzymatic activation （by xanthine oxidase） or chemical activation （by zinc） to synthesize AA-dGp adducts, and the reaction conditions were optimized. Crude extracts were analyzed by techniques of liquid chromatographyelectrospray ionization/tandem mass spectrometry （LC-MS/MS） and high accuracy mass data and isotope pattern of super high resolution Fourier transform-ion cyclotron resonance mass spectrometry （FT-ICRMS）. The quasi-molecular ion peaks of the AA-dGp adducts were obtained in the negative ion mode. Analysis by electrospray ionization/tandem mass spectrometry （ESI-MS/MS） provided useful structural information about AA-dGp adducts. AA can bind covalently to the exocyclic amino group of deoxyguanosine to form AA-dGp adducts. MS analysis is a powerful tool to detect and identify AA-dGp adducts simply, rapidly and accurately.

关 键 词：马兜铃酸-脱氧鸟苷酸加合物 合成 质谱法 

分 类 号：R917[医药卫生—药物分析学]