Synthesis And Analytical Applications Of Novel Multi-label Mass Spectrometry Probes

Ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)technology is widely used in metabolite analysis due to its strong chromatographic separation ability and high quantitative level.The development and application of sample pretreatment technology occupies an important position in the field of analytical chemistry.In the traditional isotope dilution method,there is a problem that isotope internal standards are expensive or difficult to synthesize.The stable isotope labeling derivatization technology further ensures the accuracy and reliability of the analysis results on the basis of solving this problem.The multi-label mass spectrometry probe derivatization technology is developed on the basis of stable isotope labeling derivatization technology.It can carry out differential structural modification for multiple samples to be tested,and realize multi-channel qualitative and quantitative analysis in the multiple reaction monitoring(MRM)mode of UHPLC-MS/MS.The multi-label mass spectrometry probe derivatization technology also solves the problem of expensive or difficult to synthesize isotope internal standards,and also realizes high specificity,high sensitivity,high accuracy and high throughput analysis and determination.Excessive derivatization reagents in the of multi-label mass spectrometry probe derivatization technology will interfere with the subsequent analysis and quantification.The magnetic dispersion solid-phase extraction(MDSPE)technology based on molecularly imprinted polymers has significant advantages in the field of sample pretreatment due to its specific,efficient adsorption capacity and easy operation under the interference of complex matrix.The application of multi-label mass spectrometry probes and MDSPE material in UHPLCMS/MS is of great significance for the dynamic monitoring of target compounds in metabolic analysis and the screening of disease markers.The specific research content of this paper is as follows:Chapter 1: Briefly describes the principles and application progress of UHPLCMS/MS,derivatization technology,magnetic dispersion solid phase extraction technology.Chapter 2: For the first time,a series of mass spectrometer probes based on activated ester of levofloxacin carboxylic acid were designed and synthesized,combined with magnetic dispersion solid-phase extraction technology using molecularly imprinted polymer as adsorbent and UHPLC-MS/MS technology,and used in human plasma high-throughput qualitative and quantitative analysis of Glucosylsphingosine(Glc S)and galactosylsphingosine(Gal S).The results show that the molecularly imprinted polymer synthesized based on dummy template(DMMIPs)technology can better achieve the efficient extraction and enrichment of Glc S and Gal S derivatives.The application of DMMIPs combined with multi-label mass spectrometry probes greatly improves the analytical performance of Glc S and Gal S,such as throughput,specificity,sensitivity,and accuracy.This method provides a new idea for the detection of Glc S and Gal S in plasma.Chapter 3: A 12-plex pretreatment technology of samples based on multi-label mass spectrometry probe derivatization combined with magnetic solid phase dispersion extraction(MTCIL-MDSPE)was developed.Among them,a specific mass spectrometry probe labeled standard was used as an internal standard,and the 12-plex mass spectrometry probes were used to label twelve urine samples.DMMIPs synthesized using structural analogs of targeted derivatives as templates were used for the extraction and enrichment of target derivatives in mixed urine samples.Finally,combined with the MRM monitoring mode of UHPLC-MS/MS,it was applied to the analysis of sarcosine in human uirne.This strategy has been successfully applied to the high-throughput qualitative and quantitative analysis of sarcosine in the urine of prostate cancer patients and healthy men.