Development of a Surface Sampling Probe Method Detected with Air Flow-assisted Ionization Mass Spectrometry for the Distribution of Drug in Rat Tissue
  
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DOI:10.3969/j.issn.1004-4957.年份.月份
KeyWord:surface sampling probe  air flow assisted ionization  mass spectrometry  whole body section  drug distribution
  
AuthorInstitution
罗志刚,何菁菁,贺玖明,马双刚,庾石山,再帕尔·阿不力孜 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
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Abstract:
      An apposing liquid microjunction surface sampling probe(LMJ-SSP) system combined with air flow-assisted ionization(AFAI) was developed for the biopharmaceutical 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 applied in the distribution analysis of S-(+)-deoxytylophorinidine(CAT),a potential anticancer agent,in the main organs of a whole-body rat tissue section.The key parameters of the LMJ-SSP-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∶H2O,70∶30,containing 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 surface analysis of analytes in complex matrix of large objects remotely under ambient environment without intensive sample preparations,which can be used for preliminary experiment prior to IMS research.By providing the information about the organs which should be paid more attention,the varied 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.
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