基于高分辨质谱技术的整体动物体内药物成像分析新方法研究  

Development of a Novel Imaging Method for Whole-Body Animal Biopharmaceutical Analysis Using High Resolution Mass Spectrometry Technique

作　　者：罗志刚[1] 贺玖明[1] 李铁钢[1] 周帜 黄罗娇 张瑞萍[1] 马双刚[1] 庾石山[1] 再帕尔.阿不力孜 

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 [2]中央民族大学生物成像与系统生物学研究中心,北京100081

出　　处：《质谱学报》2017年第4期417-424,共8页Journal of Chinese Mass Spectrometry Society

基　　金：国家自然科学基金项目(81373370;21335007);重大科学仪器设备开发专项(2016YFF0100304)资助

摘　　要：质谱分子成像技术作为体内药物分析的新兴工具受到越来越多的关注,其中生物体内复杂基质的干扰是面临的关键问题之一。本研究利用高分辨质谱技术的优势,采用空气动力辅助离子化质谱成像方法(AFAI-MSI),建立了高特异性的整体动物体内药物成像分析新方法,以提高体内药物成像分析结果的准确性和可靠性。以候选新药右旋娃儿藤宁碱(S-(+)-deoxytylophorinidine,CAT)为研究对象,采用高分辨质谱全扫描与靶向扫描相结合的方式,对整体动物体内药物的分布进行AFAI-MSI分析。结果表明,该方法能够准确地反映药物特异性分布和处置情况。通过一次质谱成像实验,从整体动物水平同时实现了候选新药体内分布和药物干预下内源性代谢物的成像分析,为候选新药的早期研发提供思路与手段。Mass spectrometry imaging （MSI） is a label-free molecular imaging technique whereby to simultaneously measure and map multiple biomolecules directly from tissue sections. It is reported that MSI analysis of metabolites has undergone a fast develop-ment and has been developed into a powerful tool for drug development and discovery in recent years. However, some problems, such as molecule covering range, sensitivity of metabolite detection, and the interference from the complicated biological matrix are still remaining as challenges for current MSI technologies. To tackle with these prob-lems ,our group previously developed an air flow assisted ionization （AFAI） MSI platform, and successfully applied it on in vivo pharmaceutical analysis. Aiming at increasing the sensitivity and specificity of in vivo pharmaceutical analysis, an integrated MSI method to simultaneously image drug and endogenous metabolites in whole body tissue section was developed using AFAI-MSI in a full mass scan mode. This method can acquire not only the distribution of drugs and its metabolites, but also enormous va-rious endogenous metabolites in one experiment, as resulted to obtain in situ spatial and chemical information of parent drugs and metabolites in whole-body tissue sections; and the target organs of drugs can be directly mapped. Based on our previously reported AFAI ion source, we modified the interface to couple the AFAI ion source on a Q-〇 rbi- trap mass spectrometer, and constructed an new AFAI-MSI device, and further specific-ally programed the data features （high resolution MS data） into our MSI software, finally achieved rapid and reliable MSI analysis of tissue section, along with high stabili-ty and accuracy information for metabolite identification. The drug candidate S-（ ＋ ）- deoxytylophorinidine （CAT） was selected to study the spatial distribution in rat. AFAI- MSI analysis was performed for the administered tissue sections along with the d

关 键 词：质谱成像 空气动力辅助离子化(AFAI) 药物分析 代谢产物 内源性代谢物 

分 类 号：O657.63[理学—分析化学]