Ion strength virtual correction and quantitative mass spectrum imaging analysis method of in-vivo drugs

Abstract

The invention belongs to the technical field of biological analysis and detection, and relates to an ion strength virtual correction and quantitative mass spectrum imaging analysis method of drugs, which can be used for exploring the accurate content of drug molecules at different spatial positions in a living body. According to the method, isotope labeled drugs are not needed to be used as internal standards, endogenous metabolite ions of each mass spectrum image acquisition pixel point are used as natural internal standards, a multiple regression prediction model of the endogenous metaboliteions-drug relative matrix effect is established, virtual correction of the biological tissue specific matrix effect is achieved, and quantitative calculation of drug content in any area in a whole biological tissue sample is completed through a standard curve established by a standard reference sample. The invention provides an intuitive and visual quantitative imaging method for quickly acquiring absorption, distribution, metabolism and excretion information of candidate drugs in a body, predicting potential toxic and side effects and the like.

Description

technical field [0001] The invention belongs to the technical field of biological analysis and detection, and relates to a virtual correction and quantitative mass spectrometry imaging analysis method of drug ion intensity in vivo, which can be applied to explore the accurate content of drug molecules in different spatial positions of biological tissues. [0002] technical background [0003] Mass Spectrometry Imaging (MSI) is a new molecular imaging technology that combines desorption ionization technology with mass spectrometry detection and analysis. Through desorption ionization and mass spectrometry data collection line by line / point on the surface of the sample to be tested (mostly biological tissue), the intensity values ​​of ions with different mass-to-charge ratios are sequentially reconstructed into a two-dimensional data array according to the spatial position and displayed in the form of an image . It does not require radioactive isotopes, fluorescent or immunola...

AI Technical Summary

Problems solved by technology

However, for the large number of candidate compounds in the preclinical drug discovery stage, due to their novel structures, there is often a lack of commercially available isotope-labeled compounds as calibration internal standards

If empirical constant correction is used, it is necessary to construct multiple standard curves corresponding to different organ tissues to obtain the quantitative conversion factor of the "content-ionic strength" of the candidate drug in each organ tissue. Calibration and accurate quantification cannot be achieved in some tissue areas in animals where corresponding standard curves have not been established

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