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CN-122016990-A - Method and device for rapid mass spectrum detection of multi-component compounds in body fluid

CN122016990ACN 122016990 ACN122016990 ACN 122016990ACN-122016990-A

Abstract

The invention discloses a rapid mass spectrum detection method and device for multi-component compounds in body fluid, which relate to the technical field of mass spectrum detection and comprise the steps of reserving an analytical liquid film inside an ion source, gradually volatilizing a solvent in the analytical liquid film under the conditions of an electric field of the ion source, thermal assistance and airflow assistance, ionizing a target compound in the analytical liquid film to form target compound ions, sequentially releasing the target compound ions according to physical migration and energy response difference and guiding the target compound ions to a mass analysis area to form an ion signal time sequence, carrying out mass spectrum detection on the ion signal time sequence, and collecting characteristic ion signals of the target compound ions and stable isotope internal standard ions through a multi-reaction monitoring mode.

Inventors

  • ZHAO YEQI

Assignees

  • 中验检测股份有限公司

Dates

Publication Date
20260512
Application Date
20260316

Claims (10)

  1. 1. A rapid mass spectrum detection method of multi-component compounds in body fluid is characterized by comprising the following steps of, Collecting a body fluid sample of a detected object, transferring the body fluid sample to a functional treatment interface of a preset stable isotope internal standard, and forming a sample surface area at the functional treatment interface adjacent to an ion source inlet; Positioning a sample surface area in an ion source, releasing an analysis solvent into the sample surface area by a sampling needle in the ion source, enabling the end part of the sampling needle to contact the sample surface area, and forming an analysis liquid film carrying a target compound and a stable isotope internal standard in the sample surface area through the analysis solvent; The method comprises the steps of reserving an analytic liquid film in an ion source, gradually volatilizing a solvent in the analytic liquid film under the conditions of an ion source electric field, heat assistance and airflow assistance, ionizing a target compound in the analytic liquid film to form target compound ions, sequentially releasing the target compound ions according to physical migration and energy response difference, and guiding the target compound ions to a mass analysis area to form an ion signal time sequence; and carrying out mass spectrum detection on the ion signal time sequence, collecting characteristic ion signals of the target compound ions and the stable isotope internal standard ions through a multi-reaction monitoring mode, completing qualitative identification, determining a target compound concentration interval based on a signal intensity ratio, and generating a structural detection result.
  2. 2. The method for rapid mass spectrometry of a multi-component compound in a body fluid according to claim 1, wherein the body fluid sample of the subject is obtained by directly dipping the body fluid on the body surface of the subject with a sampling needle.
  3. 3. A method for rapid mass spectrometry detection of multicomponent compounds in body fluids according to claim 1, wherein the sample surface area is formed by: introducing a body fluid sample collected by a sampling needle into a functional treatment interface of a preset stable isotope internal standard, forming body fluid sample liquid drops on the functional treatment interface and limiting the body fluid sample liquid drops into a sample surface area; Exposing the body fluid sample in the sample surface area to an acidic chemical environment of the functionalized treatment interface to cause conformational changes and aggregation deactivation of macromolecular components in the body fluid sample; contacting the body fluid sample in the sample surface area with a functional material of the functional treatment interface to retain non-target matrix components in the body fluid sample at the functional treatment interface and weaken interference; The target compound and the stable isotope internal standard in the sample surface area are enriched and kept in the sample surface area at the functionalization processing interface.
  4. 4. The method for rapid mass spectrometry detection of multicomponent compounds in body fluid according to claim 1, wherein the forming of the analytical liquid film carrying the target compound and the stable isotope internal standard comprises: Introducing an resolving solvent into the sample surface area through the sampling needle in the ion source, enabling the end of the sampling needle to touch the sample surface area, and forming a local solvent coating layer on the sample surface area; and desorbing the target compound and the stable isotope internal standard in the sample surface area by utilizing the local solvent coating layer, and maintaining the liquid film form of the local solvent coating layer in the ion source to form an analysis liquid film for bearing the target compound and the stable isotope internal standard.
  5. 5. The method for rapid mass spectrometry detection of multi-component compounds in body fluids according to claim 1, wherein the formation of target compound ions is specifically: Maintaining an analytic liquid film carrying a target compound and a stable isotope internal standard at an analytic position inside an ion source, and establishing an electric field acting on the analytic liquid film inside the ion source; Applying heat assistance and introducing airflow assistance to an analysis position in the ion source, driving the analysis solvent in the analysis liquid film to gradually volatilize and maintaining the analysis liquid film in a volatilizable state; And maintaining the action of an electric field in the ion source in the gradual volatilization process of the analytical liquid film, so that the target compound in the analytical liquid film is ionized and target compound ions are formed.
  6. 6. The method for rapid mass spectrometry of multicomponent compounds in body fluid according to claim 1, wherein the time series of ion signals are formed by: setting an ion migration path in the ion source and applying a segmented electric field on the ion migration path to enable the target compound ions to migrate in a controlled manner on the ion migration path; Synchronously applying heat assistance and air flow assistance on an ion migration path, and changing the time distribution of target compound ions released from an analytical liquid film into a gas phase so that the target compound ions with different physicochemical properties are sequentially released according to physical migration and energy response difference; And arranging a guide electrode at the tail end of the ion migration path, applying a guide electric field, guiding the ions of the target compound released in sequence to a mass analysis area, and forming an ion signal time sequence in the time dimension.
  7. 7. The method for rapid mass spectrometry detection of multi-component compounds in body fluid according to claim 1, wherein the characteristic ion signals of target compound ions and stable isotope internal standard ions are collected through a multi-reaction monitoring mode, and specifically comprises the following steps: Setting a multi-reaction monitoring mode in the mass spectrum detection process and presetting a parent ion-child ion conversion relation corresponding to the target compound ions; synchronously collecting a parent ion signal and a child ion signal of target compound ions in a multi-reaction monitoring mode and recording signal intensity; and synchronously collecting a parent ion signal and a child ion signal of the stable isotope internal standard ion in a multi-reaction monitoring mode, and recording the signal intensity.
  8. 8. The method for rapid mass spectrometry detection of multi-component compounds in body fluid according to claim 1, wherein the determining the concentration interval of the target compound is specifically: extracting characteristic ion signal intensity of the target compound ions from the parent ion signal and the child ion signal of the target compound ions; extracting characteristic ion signal intensity of the stable isotope internal standard ion from a parent ion signal and a child ion signal of the stable isotope internal standard ion; Calculating the signal intensity ratio of the characteristic ion signal intensity of the target compound ion to the characteristic ion signal intensity of the stable isotope internal standard ion, and determining the concentration interval of the target compound according to the corresponding relation of the preset concentration interval.
  9. 9. The method for rapid mass spectrometry detection of multicomponent compounds in body fluid according to claim 1, wherein the generation of the structured detection result is specifically: Extracting a time sequence signal corresponding to the target compound ion from the ion signal time sequence and establishing a target compound ion time sequence record; correspondingly associating the target compound ion time series record with a target compound concentration interval to form a target compound detection record; and uniformly packaging the target compound detection records and generating a structured detection result.
  10. 10. A rapid mass spectrum detection device for multi-component compounds in body fluid based on the rapid mass spectrum detection method for multi-component compounds in body fluid according to any one of claims 1 to 9 is characterized by comprising the following steps, The acquisition module acquires a body fluid sample of the detected object, transfers the body fluid sample to a functional treatment interface of a preset stable isotope internal standard, and forms a sample surface area at the functional treatment interface adjacent to the ion source inlet; the analysis module is used for positioning the sample surface area in the ion source to release analysis solvent to the sample surface area, enabling the end part of the sampling needle to contact the sample surface area, and forming an analysis liquid film carrying the target compound and the stable isotope internal standard in the sample surface area through the analysis solvent; The detection module is used for reserving an analysis liquid film in the ion source, gradually volatilizing a solvent in the analysis liquid film under the conditions of an ion source electric field, heat assistance and airflow assistance, ionizing a target compound in the analysis liquid film to form target compound ions, sequentially releasing the target compound ions according to physical migration and energy response difference and guiding the target compound ions to a mass analysis area to form an ion signal time sequence; And the output module is used for carrying out mass spectrum detection on the ion signal time sequence, collecting characteristic ion signals of target compound ions and stable isotope internal standard ions through a multi-reaction monitoring mode, completing qualitative identification, determining a target compound concentration interval based on a signal intensity ratio and generating a structural detection result.

Description

Method and device for rapid mass spectrum detection of multi-component compounds in body fluid Technical Field The invention relates to the technical field of mass spectrometry detection, in particular to a rapid mass spectrometry detection method and device for multi-component compounds in body fluid. Background In the field of mass spectrometry, detection techniques for multi-component compounds in body fluids have undergone an evolution from traditional separation coupling to ambient ionization and high resolution instrumentation. Soft ionization technologies such as electrospray ionization and matrix-assisted laser desorption ionization are adopted, so that mild ionization of macromolecules and polar compounds is realized, and breakthrough of biological sample analysis is promoted. Subsequently, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry become mainstream, and are used for separation, qualitative and quantitative of drug metabolites, drug residues and endogenous metabolites in body fluids (such as blood, urine, saliva). With the development of high-resolution mass spectrometers, detection accuracy and multiplex analysis capability are further improved, hundreds of compounds are supported to be monitored simultaneously, and metabonomics and toxicology research are remarkably promoted. However, the existing mass spectrum detection technology can be improved, firstly, the intrinsic ion sequential release mechanism is lacking, compound ions with different physicochemical properties cannot be distinguished naturally in the time dimension, so that the resolution of isomers or similar mass compounds depends on external chromatography or additional post-treatment, the operation complexity and the instrument dependence are further increased, and secondly, the integration of stable isotope internal standards in the existing method can correct part of matrix effects, but the physical and chemical environments of the internal standards and target compounds are often not completely consistent, and the reliability of a quasi-quantitative result is affected. Disclosure of Invention The present invention has been made in view of the above-described problems occurring in the prior art. Therefore, the invention provides a rapid mass spectrometry detection method for multi-component compounds in body fluid, which solves the problems that an inherent ion sequential release mechanism is lacked and the physical and chemical environments of an internal standard and a target compound are often not completely consistent. In order to solve the technical problems, the invention provides the following technical scheme: In a first aspect, the present invention provides a method for rapid mass spectrometry detection of a multicomponent compound in a body fluid, comprising, Collecting a body fluid sample of a detected object, transferring the body fluid sample to a functional treatment interface of a preset stable isotope internal standard, and forming a sample surface area at the functional treatment interface adjacent to an ion source inlet; Positioning a sample surface area in an ion source, releasing an analysis solvent into the sample surface area by a sampling needle in the ion source, enabling the end part of the sampling needle to contact the sample surface area, and forming an analysis liquid film carrying a target compound and a stable isotope internal standard in the sample surface area through the analysis solvent; The method comprises the steps of reserving an analytic liquid film in an ion source, gradually volatilizing a solvent in the analytic liquid film under the conditions of an ion source electric field, heat assistance and airflow assistance, ionizing a target compound in the analytic liquid film to form target compound ions, sequentially releasing the target compound ions according to physical migration and energy response difference, and guiding the target compound ions to a mass analysis area to form an ion signal time sequence; and carrying out mass spectrum detection on the ion signal time sequence, collecting characteristic ion signals of the target compound ions and the stable isotope internal standard ions through a multi-reaction monitoring mode, completing qualitative identification, determining a target compound concentration interval based on a signal intensity ratio, and generating a structural detection result. As a preferable scheme of the rapid mass spectrometry detection method of the multi-component compound in the body fluid, the body fluid sample of the detected object is obtained by directly dipping the body fluid of the detected object through a sampling needle. As a preferred embodiment of the method for rapid mass spectrometry detection of multicomponent compounds in body fluids according to the invention, the sample surface area is formed by: introducing a body fluid sample collected by a sampling needle into a functional treatment interface of a pres