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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。
The application of parallel droplet micro-connected surface sampling probe (LMJ-SSP) mass spectrometry in the analysis of drug distribution in rats was studied. Mass spectrometry detection using homemade atmospheric open aerodynamic assisted ionization mass spectrometry (AFAI-MS) technology. The LMJ-SSP system was established by optimizing its main probe system parameters (aspiration capillary length 24 cm; effluent flow rate 7.5 μL / min; sampling end distance from the slice surface 20 μm) and 10-hydroxycamptothecin The drugs in the tissue were detected by adding drugs to the blank rat tissue sections. The stability of the LMJ-SSP-AFAI-MS method and the parallelism of the test results were also examined. On this basis, we took the anti-cancer drug candidate S - (+) - desoxyvalerine (CAT) as the research object and used the tail vein injection to make whole animal tissue sections. The LMJ-SSP -AFAI-MS method was used to analyze the content distribution of the drugs in the major organs in the whole tissue sections of rats. The results provided the basis for the analysis of the efficacy and toxic side effects of CAT. The LMJ-SSP-AFAI-MS method is suitable for the detection of mass spectrometry on the surface of large volume objects under the open environment, and has the characteristics of high sensitivity and unaffected by complex matrix. It is expected to provide a new method for the analysis of the distribution characteristics of candidate new drugs in animals .