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

An analysis method and ionic strength technology, applied in the analysis of materials, material analysis by electromagnetic means, and measurement devices, can solve the problems of lack of isotope-labeled compounds to calibrate internal standards, the inability to achieve calibration and accurate quantification, time-consuming and labor-intensive problems, and achieve Shorten the cycle of sample preparation and analysis, close toxic and side effects, and reduce the effect of error

Active Publication Date: 2019-07-23
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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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

Method used

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

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Embodiment Construction

[0057] The present invention takes the quantitative mass spectrometry imaging analysis of the anti-tumor drug candidate LXY6006 in whole animals as an example, and the overall process of quantitative analysis is as follows: figure 1 As shown, the specific implementation steps will be described in detail, but this embodiment does not limit the present invention in any way.

[0058] 1. Preparation of Whole Animal Samples

[0059] Select a tumor-bearing Balb / C nude mouse, inject LXY6006 / HP-β-CD inclusion complex preparation into the tail vein at a dose of 6.0 mg / kg, and put it to death under anesthesia in ether environment 30 minutes after administration , a Leica CM3600 large-scale cryostat was used to prepare frozen sections of whole animals with a thickness of 25 μm for AFAI-MSI analysis.

[0060] 2. Preparation of Mock Tissue Samples

[0061] 2.1 Preparation of blank biological tissue: Weigh an appropriate amount of fresh organ / tissue, add a certain concentration of low mel...

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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...

Claims

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Application Information

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IPC IPC(8): G01N27/62
CPCG01N27/62G16B40/00Y02A90/10
Inventor 再帕尔·阿不力孜宋肖炜贺玖明罗志刚孙成龙厉欣黄罗娇张瑞萍
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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