大鼠组织中药物分布的表面采样探针质谱方法研究  

Development of a Surface Sampling Probe Method Detected with Air Flow-assisted Ionization Mass Spectrometry for the Distribution of Drug in Rat Tissue

作　　者：罗志刚[1] 何菁菁[1] 贺玖明[1] 马双刚[1] 庾石山[1] 再帕尔·阿不力孜[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《分析测试学报》2012年第7期757-762,共6页Journal of Instrumental Analysis

基　　金：国家自然科学基金资助项目(20827007);国家自然科学基金青年科学基金资助项目(20905057);国家重大科学仪器设备开发专项资助(2011YQ170067)

摘　　要：对并列式液滴微连接表面采样探针(LMJ-SSP)质谱技术在大鼠体内药物分布分析中的应用进行了研究。质谱检测方式采用自制的常压敞开式空气动力辅助离子化质谱(AFAI-MS)技术。通过优化其主要的探针系统参数(吸液毛细管长度24 cm;出液流速7.5μL/min;采样端距切片表面距离20μm),建立了LMJ-SSP系统,并以10-羟基喜树碱为标准品,通过在空白大鼠组织切片中添加药物的方式,对组织中的药物进行检测,并对LMJ-SSP-AFAI-MS方法的稳定性和检测结果的平行性进行了考察。在此基础上,以抗癌候选药物S-(+)-去氧娃儿藤宁碱(CAT)为研究对象,采用鼠尾静脉注射的方式给药后制作整体动物组织切片,采用LMJ-SSP-AFAI-MS方法对药物在大鼠整体组织切片中各主要脏器内的含量分布进行了分析,其结果为CAT的药效及毒副作用的解释提供了分析依据。LMJ-SSP-AFAI-MS方法适合于开放环境下大体积物体表面的质谱分析检测,且具有灵敏度高、不受复杂基体影响等特点,有望为动物体内候选新药的分布特征分析提供一种新手段。An apposing liquid microjunction surface sampling probe （ LMJ - SSP） system combined with air flow-assisted ionization （AFAI） was developed for the biopharmaeeutieal analysis. At the same time, the stability of the LMJ - SSP - AFAI - MS method was validated by the analysis of the added 10-hydroxy camptothecin in tissue section. And then the LMJ - SSP - AFAI system was ap- plied in the distribution analysis of S-（ ＋ ）-deoxytylophorlnidine（CAT）, a potential anticancer a- gent, in the main organs of a whole-body rat tissue section. The key parameters of the LMJ - 5SP - AFAI- MS method were optimized to enable stable sampling status and sensitive analysis, including length of imbibing capillary（24 cm） , composition of extraction solvent（ACN ： H20, 70 ： 30, con- taining 0. 1% FA） , flow rate of extraction solvent （ 7.5 μL/min） and gap between probe tip and sample surface （20 μm）. The distribution information of CAT obtained with the LMJ -SSP -AFAI - MS system can provide possible indication for its drug efficacy as well as side effect and toxicity, In addition, the LMJ- SSP- AFAI -MS method was demonstrated to be a sensitive tool for direct sur- face analysis of analytes in complex matrix of large objects remotely under ambient environment with- out intensive sample preparations, which can be used for preliminary experiment prior to IMS re-search. By providing the information abotat the organs which should be paid more attention, the var- ied distributions information of drugs in different organs will guide the preparations of the whole body section with all the targeted organs in one section and the optimization of whole body IMS experimental parameters. What is more, the LMJ - SSP - AFAI - MS method can provide an alternative way for the distribution analysis of drug candidates during drug discovery.

关 键 词：表面采样探针 空气动力辅助离子化 质谱分析 整体组织切片 药物分布 

分 类 号：O657.6[理学—分析化学] TQ460.72[理学—化学]