Development Of Sample Pretreatment Methods Based On Multi-label Derivatization Reagents And Application Of Liquid Chromatography-mass Spectrometry

Ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS)technology is widely used in various fields such as food safety,medical detection and analysis,environmental analysis,life sciences,and petrochemicals.This technology not only has the advantages of high performance liquid chromatography,fast analysis speed,and high detection sensitivity,but also has the advantages of high specificity and quasi-deterministic quantification of mass spectrometry.It is very friendly to the analysis and detection of complex biological samples.Stable isotope-labeled derivatization(SILD)achieves quasi-deterministic and quantitative by modifying the molecular structure to improve the sensitivity of analytical detection and the response signal of the mass spectrum.However,in actual analysis,the analysis sample size is huge,and the multi-channel stable isotope labeling derivatization(MSILD)technology can solve the above problems and improve the analysis throughput.At the same time,derivatization brings new problems.Excessive derivatization reagents seriously interfere with the analysis and detection of chromatographic mass spectrometry.Magnetic Dispersive Solid Phase Extraction Technology(MDSPE)is combined with adsorbents such as graphene oxide and molecularly imprinted polymers and applied to the sample pretreatment process.It has the advantages of simple operation,fast speed and high adsorption efficiency.This thesis mainly completed three tasks,the specific contents are as follows:Chapter One: Briefly introduces the progress of ultra-high performance liquid chromatography tandem mass spectrometry,chemical derivatization technology,stable isotope labeling derivatization technology,multi-channel stable isotope labeling derivatization technology and magnetic dispersion solid phase extraction technology.Chapter Two: For the first time,a series of novel multi-tag derivative reagents based on piperidine acid structure——stable isotope mass tags(SIMTs)labeled analytes.Combined with magnetic dispersion solid phase extraction(MDSPE)technology with graphene oxide as adsorbent and ultra high performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)technology.The technology enables the detection of free hydroxy polycyclic aromatic hydrocarbons(OH-PAHs)in human urine or plasma in 9 channels.Chapter Three: A high throughput,high selectivity,high sensitivity and high precision method was developed for the analysis of magnetic dispersion solid phase extraction and ultra high performance liquid chromatography tandem mass spectrometry with multi-label derivate coupled with molecular imprinting as adsorbent.This method has been successfully applied to the simultaneous determination of schisandrin a in rat blood and brain microdialysate.Chapter Four: A new strategy was developed to combine 4-derived stable isotope labeling derivatization with a virtual magnetic molecularly imprinted polymer(QSILD-DMMIP).UHPLC-MS/MS(MRM)specific extraction and effective determination of hydroxyproline in the serum of patients with liver fibrosis and healthy controls.This strategy can not only effectively prevent template leakage of conventional techniques in the extraction application process,but also significantly reduce matrix interference and greatly improve detection sensitivity,accuracy and analysis throughput.