Quantitative Analysis Information Extraction For Clinical Application Of LC-MS/MS

With the continuous development of science and technology,mass spectrometry technology is widely used in analytical chemistry and metrology.Liquid Chromatography-Triple Quadrupole Mass Spectrometry(LC-MS/MS)can greatly improve the analysis ability of complex sample and promote the rapid development of mass spectrometry in the medical field,making mass spectrometry technology great application potential in clinical diagnosis and precision medical detection.Based on the analysis of spectral data concentration information,this study designs and develops a complete set of spectral information extraction quantitative detection methods by analyzing the properties of LC-MS/MS data structures.This method includes original data denoising,chromatographic analysis and identification,spectral peak matching,curve fitting,and other algorithms.A kind of algorithm which depend on data characteristicof signals and noise is designed to automatically remove the noise from originalmass spectrogram.Smooth Z-score method is used with the multistage slope algorithm of target compounds,chromatographic peak of quality analysis,implementation of complex matrix samples,shoulder peak and low concentration peak,and tailing peak of accurate identification.Then,spectrum peak retention time correction is performed,and the measurement and weights of curve fitting are discussed.Finally,a standard curve for quantitative analysis is established.In this paper,the detection of 25-hydroxyvitamin D in human serum with the current clinical test procedure is taken as an example to verify the self-developed algorithm and form a set of quantitative calibration under the liquid chromatography-triple quadrupole mass spectrometry multiple reaction monitoring(MRM)scanning mode.Analyze algorithm packages to reduce optimization time and improve the automation level of spectral data processing.For the detection of clinical complex matrix samples,especially endogenous metabolites,based on the general spectrum processing algorithm,taking the detection of vitamins in human serum as an example,an analytical method for human endogenous metabolite was explored.A mixed human serum matrix was prepared by adding standard substances followed by background subtraction of endogenous substances,and another simulating matrix substrate was made of bovine serum albumin(BSA).The linear correlation coefficients of the two methods are above 0.996.The recoveries for the actual samples spiked at low and high concentrations were between 90% and 112%.Therefore,for the endogenous metabolites from human body,the accurate analysis on the matrix matched between the standard sample and the sample to test could be achieved by adding the standand substance and deducting the background from the human serum matrix,which is beneficial to the convenient diagnosis on clinical related diseases.Based on the universal quantitative data processing and analysis algorithm developed in this paper,the method of detecting and analyzing endogenous metabolites in complex matrix samples of human body is designed,and the special operation software for specific clinical detection mass spectrometer is designed.Finally,the LCMS/MS application software system based on the medical mass spectrometer software platform was formed,which has been applied to the product engineering prototype of Suzhou Medical Engineering Institute Tianjin Industrial Research Institute Medical Triple Quadrupole Mass Spectrometer Development Project.