A method for extracting peaks from time-of-flight mass spectrometry for drug detection

Abstract

The present invention relates to the field of data processing technology, and in particular to a method for extracting a time-of-flight mass spectrometry peak for drug detection, including: obtaining ion source voltage data, mass spectrometer vacuum, ion flight time period, and mass spectrometry data of a drug solution; obtaining the mass spectrometer operation stability at each moment according to the ion source voltage data and mass spectrometer vacuum at each moment; obtaining the interference degree of each ion according to the mass spectrometry data of the drug solution and the ion flight time period, combined with the mass spectrometer operation stability, further adaptively generating a local window length of the ion, thereby removing the baseline drift in the mass spectrometry data of the drug solution, and extracting the mass spectrometry peak. The present invention adaptively generates a decomposed local window by analyzing the operation of the mass spectrometer, combined with the influence of the baseline drift on the mass spectrometry data, thereby avoiding the loss of mass spectrometry information while removing the baseline drift therein, thereby improving the accuracy of extracting the mass spectrometry peak.

Description

Technical Field

[0001] The present invention relates to the technical field of data processing, and in particular to a method for extracting time-of-flight mass spectrometry peaks for drug detection. Background Art

[0002] Drug mass spectrometry is an effective means of analyzing the drug components and content in samples through mass spectrometry technology. In the process of drug mass spectrometry, the time-of-flight mass spectrometry (TOF-MS) is highly sensitive to environmental changes, sample characteristics and instrument status, which leads to baseline drift in the detected mass spectrometry data, resulting in inaccurate extracted spectral peaks. In order to accurately extract mass spectrometry peaks, it is necessary to remove the baseline drift in the mass spectrometry data. The traditional local decomposition method of LMD (Local Mean Decomposition) is used to remove the baseline drift in the mass spectrometry data. A local window needs to be set to smooth the data in the window, thereby extracting the trend part of the data in the window and removing the baseline drift. However, when setting the local window, if the local window is too large, some low-frequency information in the window will be identified as part of the baseline drift and removed, resulting in the loss of some mass spectrometry information. If the local window is too small, the baseline drift information in the window cannot be effectively captured. Summary of the invention

[0003] The present invention provides a time-of-flight mass spectrometry peak extraction method for drug detection to solve the existing problem that the traditional LDM local decomposition method cannot avoid the loss of mass spectrum information while removing the baseline drift in the mass spectrum data.

[0004] A method for extracting a time-of-flight mass spectrometry peak for drug detection of the present invention adopts the following technical solution:

[0005] The following steps are involved:

[0006] Acquire ion source voltage data, mass spectrometer vacuum degree, ion flight time period, and mass spectrum data of drug solution;

[0007] According to the ion source voltage data and the mass spectrometer vacuum degree at each moment, the operation stability of the mass spectrometer at each moment is obtained;

[0008] Fitting the mass spectrum data of the drug solution to obtain the mass spectrum curve of the drug solution, and dividing the mass spectrum curve into a number of mass spectrum curve segments; obtaining the degree of ionization non-uniformity of each mass spectrum curve segment according to the degree of similarity between each mass spectrum curve segment and its adjacent mass spectrum curve segment, combined with the distribution of all ions in each mass spectrum curve segment; obtaining the degree of interference of each ion according to the degree of ionization non-uniformity of each mass spectrum curve segment corresponding to each ion, the mass spectrometer operation stability at each moment in the flight time period of each ion, and the high-frequency components in the mass spectrum curve segment corresponding to each ion, combined with the mass-to-charge ratio of each ion;

[0009] According to the interference degree of each ion and the mass spectrum curve segment corresponding to each ion, the local window length of each ion is obtained; the mass spectrum data of the drug solution is decomposed according to the local window length of each ion, the baseline drift in the mass spectrum data of the drug solution is removed, and the mass spectrum peak is extracted.

[0010] Preferably, the method of acquiring the ion source voltage data, the mass spectrometer vacuum degree, the ion flight time period and the mass spectrum data of the drug solution includes:

[0011] The drug to be tested is dissolved in a solvent to obtain a sample solution, and the sample solution is filtered using a filter membrane to obtain a drug solution; mass spectrum data of the drug solution and the flight time period of each ion are obtained by a time-of-flight mass spectrometer;

[0012] A voltage sensor is installed at the ion source, and a vacuum gauge is installed inside the time-of-flight mass spectrometer. In the process of obtaining mass spectrum data of a drug solution using the time-of-flight mass spectrometer, the ion source voltage data and the vacuum degree of the mass spectrometer are collected at each moment.

[0013] Preferably, the method of obtaining the operation stability of the mass spectrometer at each moment according to the ion source voltage data and the mass spectrometer vacuum degree at each moment includes the following specific methods:

[0014] For At this moment, Centered on the moment, construct a The size of the neighborhood window is used as the The neighborhood window at the moment, is the preset neighborhood window size; The mass spectrometer vacuum degree in the neighborhood window at the moment is Fourier transformed to obtain The spectrum of the mass spectrometer vacuum degree in the neighborhood window at the moment is obtained, and the variance of all frequencies in the spectrum is obtained, which is recorded as Vacuum degree fluctuation factor at each moment;

[0015] The ion source voltage data was fitted using the least squares method to obtain the ion source voltage curve. The derivative of the ion source voltage curve at the moment The vacuum fluctuation factor at the moment and the The vacuum degree of the mass spectrometer at the moment The stability of mass spectrometer operation at each moment.

[0016] Preferably, the obtaining The specific calculation formula for the mass spectrometer operation stability at each moment is:

[0017]

[0018] In the formula, Indicates The operational stability of the mass spectrometer at each moment; Indicates The vacuum degree of the mass spectrometer at a certain moment; Indicates Vacuum degree fluctuation factor at each moment; Indicates The derivative of the ion source voltage curve at a certain moment; Represents the absolute value function.

[0019] Preferably, the mass spectrum data of the drug solution are fitted to obtain a mass spectrum curve of the drug solution, and the mass spectrum curve is divided into a plurality of mass spectrum curve segments, including the specific method of:

[0020] The mass spectrometry signal of the drug solution is curve fitted using the least squares method to obtain the mass spectrometry curve of the drug solution. All the minimum points in the mass spectrometry curve are used as segmentation points to divide the mass spectrometry curve into several mass spectrometry curve segments, and the mass-to-charge ratio corresponding to the maximum point in each mass spectrometry curve segment is used as the target mass-to-charge ratio of each mass spectrometry curve segment.

[0021] Preferably, the degree of ionization non-uniformity of each mass spectrum curve segment is obtained according to the degree of similarity between each mass spectrum curve segment and its adjacent mass spectrum curve segment, in combination with the distribution of all ions in each mass spectrum curve segment, and the specific method includes:

[0022] For The mass spectrum curve segment will be The mass spectrum curve segment adjacent to the mass spectrum curve segment is recorded as The neighborhood curve segment of the mass spectrum curve segment; The mass spectrum segment and The target mass-to-charge ratio in the neighboring curve segments of the mass spectrum curve segment, combined with the The skewness, excess kurtosis and intensity of all ions of the mass spectrum curve segment are obtained; The degree of ionization inhomogeneity of a mass spectrum curve segment.

[0023] Preferably, the obtaining The ionization inhomogeneity of each mass spectrum curve segment includes the following specific calculation formula:

[0024]

[0025] In the formula, Indicates The degree of ionization inhomogeneity of each mass spectrum curve segment; Indicates The skewness of each mass spectrum segment; Indicates The excess kurtosis of each mass spectrum curve segment; Indicates The average intensity of all ions in a mass spectrum segment; Indicates The number of neighboring curve segments of a mass spectrum curve segment; Indicates The target mass-to-charge ratio in each mass spectrum segment; Indicates The ion mass corresponding to the target mass-to-charge ratio in each mass spectrum curve segment; Indicates The ion charge number corresponding to the target mass-to-charge ratio in each mass spectrum curve segment; Indicates The first segment of the mass spectrum The target mass-to-charge ratio in the neighborhood curve segments; Indicates The first segment of the mass spectrum The ion mass corresponding to the target mass-to-charge ratio in each neighborhood curve segment; Indicates The first segment of the mass spectrum The number of ion charges corresponding to the target mass-to-charge ratio in each neighborhood curve segment; Represents the absolute value function.

[0026] Preferably, the obtaining of the interference degree of each ion includes the following specific methods:

[0027] For In the mass spectrum segment ions, for The mass spectrum curve segment is Fourier transformed to obtain the The spectrum of the mass spectrum curve segment is The amplitude and frequency in the spectrum diagram of the mass spectrum curve segment are obtained. High-frequency energy factor of each mass spectrum segment;

[0028] According to In the mass spectrum curve segment The stability of the mass spectrometer operation during the flight time of the ion, combined with the In the mass spectrum curve segment The mass-to-charge ratio of the ion is The high-frequency energy factor of the mass spectrum curve segment is obtained In the mass spectrum curve segment The degree of interference of an ion.

[0029] Preferably, the obtaining In the mass spectrum curve segment The specific calculation formula for the interference degree of each ion is as follows:

[0030]

[0031] In the formula, Indicates In the mass spectrum curve segment The degree of interference of individual ions; Indicates The degree of ionization inhomogeneity of each mass spectrum curve segment; Indicates In the mass spectrum curve segment The mass-to-charge ratio of the ions; Indicates In the mass spectrum curve segment The mass of an ion; Indicates In the mass spectrum curve segment The number of ion charges; Indicates In the mass spectrum curve segment The number of moments in the flight time period of an ion; Indicates In the mass spectrum curve segment The flight time of the ion The mass spectrometer operation stability corresponding to each moment; represents the maximum normalization function; Indicates The amplitude of the maximum frequency in the spectrum of each mass spectrum curve segment; Indicates The maximum frequency in the spectrum of each mass spectrum segment; Indicates The high-frequency energy factor of each mass spectrum segment, represents the linear normalization function.

[0032] Preferably, the method of obtaining the local window length of each ion according to the interference degree of each ion and combining the mass spectrum curve segment corresponding to each ion includes the following specific methods:

[0033] For any ion, the mass spectrum curve segment corresponding to the ion is used as the reference curve segment. According to the mass-to-charge ratio in the reference curve segment and the length of the reference curve segment, combined with the interference degree of the ion, the local window length of the ion is obtained. The specific calculation formula is:

[0034]

[0035] In the formula, represents the local window length of the ion; Indicates the degree of interference of the ion; represents the definite integral of the reference curve segment; Indicates the length of the datum curve segment.

[0036] The beneficial effects of the technical solution of the present invention are as follows: the present application obtains the operating stability of the mass spectrometer by analyzing the ion source voltage data and the mass spectrometer vacuum degree; the more unstable the operation of the time-of-flight mass spectrometer is, the more it will cause the baseline drift of the collected mass spectrum data to occur; by analyzing the operating stability of the mass spectrometer at each moment during the flight time period of each ion, the interference degree of the ion is evaluated; since the uneven ionization of the drug will affect the stability of the baseline in the mass spectrum data, thereby causing the baseline drift of the mass spectrum data, it is necessary to combine the uneven degree of drug ionization to evaluate the interference degree of the ion; and since the flight mass spectrometer will generate high-frequency noise during operation, thereby affecting the Mass spectrometry data, therefore, needs to be acquired based on its high-frequency components to determine the degree of interference to the ions; and because ions with a small mass-to-charge ratio are more susceptible to the majority of high-frequency noises than ions with a large mass-to-charge ratio, when quantifying the degree of interference to the ions through the high-frequency components of the ions and the stability of the mass spectrometer operation during the flight time period of the ions, it is necessary to further combine the mass-to-charge ratio of the ions to more accurately assess the degree of interference to the ions, and ultimately obtain the degree of interference to the ions; based on the degree of interference to the ions, a local window for each ion is adaptively generated, thereby achieving the goal of removing the baseline drift in the mass spectrometry data while avoiding the loss of mass spectrometry information, thereby improving the accuracy of extracting mass spectrometry peaks. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0038] Figure 1 A flow chart of the steps of a method for extracting a time-of-flight mass spectrometry peak for drug detection according to the present invention;

[0039] Figure 2 Schematic diagram of the mass spectrum curve corresponding to uneven ionization. DETAILED DESCRIPTION

[0040] In order to further explain the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the specific implementation method, structure, characteristics and effects of the time-of-flight mass spectrometry peak extraction method for drug detection proposed by the present invention are described in detail below in combination with the accompanying drawings and preferred embodiments. In the following description, different "one embodiment" or "another embodiment" does not necessarily refer to the same embodiment. In addition, specific features, structures or characteristics in one or more embodiments may be combined in any suitable form.

[0041] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0042] The specific scheme of the time-of-flight mass spectrometry peak extraction method for drug detection provided by the present invention is described in detail below with reference to the accompanying drawings.

[0043] See also Figure 1 , which shows a flow chart of the steps of a method for extracting a time-of-flight mass spectrometry peak for drug detection provided by an embodiment of the present invention, the method comprising the following steps:

[0044] Step S001: Acquire ion source voltage data, mass spectrometer vacuum degree, ion flight time period, and mass spectrum data of the drug solution.

[0045] It should be noted that drug mass spectrometry detection is an effective means of analyzing drug components and contents in samples by mass spectrometry technology. In the process of drug mass spectrometry detection, the time-of-flight mass spectrometry is highly sensitive to environmental changes, sample characteristics, and instrument status, which leads to baseline drift in the detected mass spectrometry data, and further leads to inaccurate extracted spectral peaks. Therefore, this embodiment proposes a method for extracting spectral peaks of time-of-flight mass spectrometry for drug detection; for this purpose, it is necessary to first collect the mass spectrometry data of the drug.

[0046] It should be further explained that the structure of the time-of-flight mass spectrometer includes but is not limited to: an ion source, a mass analyzer, a vacuum system, and a data processing system; the ion source is used to convert the sample to be tested into charged ions, the mass analyzer is used to separate the ions according to the mass and charge ratio of the ions, the vacuum system is used to maintain a vacuum environment to reduce the collision between ions and air molecules, and the data processing system is used to calculate the mass of the ions according to the flight time and perform corresponding data analysis.

[0047] Specifically, the drug to be tested is dissolved in a solvent to obtain a sample solution, and the sample solution is filtered using a filter membrane to obtain a drug solution; mass spectrum data of the drug solution and the flight time period of each ion are obtained by a time-of-flight mass spectrometer;

[0048] Furthermore, a voltage sensor is installed at the ion source and a vacuum gauge is installed inside the time-of-flight mass spectrometer. In the process of obtaining mass spectrum data of the drug solution using the time-of-flight mass spectrometer, the ion source voltage data and the vacuum degree of the mass spectrometer are collected at each moment. In this embodiment, 1 nanosecond is regarded as a moment.

[0049] It should be noted that since obtaining mass spectrum data using a time-of-flight mass spectrometer is a well-known prior art, it will not be described in detail in this embodiment; the horizontal axis in the mass spectrum data of the drug solution is the mass-to-charge ratio of the ions, and the vertical axis is the intensity of the ions.

[0050] At this point, the ion source voltage data, the mass spectrometer vacuum degree, the ion flight time period, and the mass spectrum data of the drug solution are obtained.

[0051] Step S002: Obtaining the operating stability of the mass spectrometer at each moment according to the ion source voltage data and the mass spectrometer vacuum degree at each moment.

[0052] It should be noted that in the process of obtaining mass spectrometry data of a drug solution through a time-of-flight mass spectrometer, when the sample to be tested is converted into charged ions through an ion source, the voltage change at the ion source will cause differences in the amount of ionization carried by the drug solution after ionization, causing the efficiency of the ion source's ionization process of the drug solution to fluctuate, thereby causing a baseline deviation in the mass spectrometry data of the drug solution.

[0053] It should be further explained that after the ion source converts the drug solution into charged ions, the charged ions will enter the mass analyzer and be separated by the mass analyzer. In the process of separating the charged ions, if the charged ions collide with air molecules, it will affect the stability of the charged ions' flight, thereby causing the mass spectrometry data of the drug solution to deviate from the baseline. Therefore, in the process of obtaining the mass spectrometry data of the drug solution, if the vacuum degree of the mass spectrometer is low or unstable, the charged ions will collide with air molecules, thereby causing the mass spectrometry data of the drug solution to deviate from the baseline. Therefore, the voltage data of the ion source and the vacuum degree of the mass spectrometer can be used to obtain the operating stability of the mass spectrometer at each moment.

[0054] Preferably, in a specific embodiment of the present invention, for At this moment, Centered on the moment, construct a The size of the neighborhood window is used as the The neighborhood window at the moment, is the preset neighborhood window size, The specific value of can be set according to the actual situation. This embodiment does not make a hard requirement. Nanoseconds are described; The mass spectrometer vacuum degree in the neighborhood window at the moment is Fourier transformed to obtain The spectrum of the mass spectrometer vacuum degree in the neighborhood window at the moment is obtained, and the variance of all frequencies in the spectrum is obtained, which is recorded as The vacuum degree fluctuation factor at each moment is not described in detail in this embodiment because Fourier transform is a well-known prior art technology. If there is a moment close to the boundary, resulting in the number of moments on its left or right being insufficient to constitute a neighborhood window, the neighborhood window is constructed based on the moment when the mass spectrometer vacuum degree actually exists.

[0055] Further, the ion source voltage data is curve fitted using the least squares method to obtain the ion source voltage curve; The derivative of the ion source voltage curve at the moment The vacuum fluctuation factor at the moment and the The mass spectrometer vacuum degree at the moment is obtained. Since the least square method and the derivative are both well-known prior arts, they will not be described in detail in this embodiment. The specific calculation formula for the mass spectrometer operation stability at a certain moment is:

[0056]

[0057] In the formula, Indicates The operational stability of the mass spectrometer at each moment; Indicates The vacuum degree of the mass spectrometer at a certain moment; Indicates Vacuum degree fluctuation factor at each moment; Indicates The derivative of the ion source voltage curve at a certain moment; Represents the absolute value function.

[0058] It should be noted that The smaller the value, the The more stable the mass spectrometer vacuum degree in the neighborhood window at each moment; The larger the value, the The internal environment of the mass spectrometer is closer to vacuum at each moment; The smaller the value, the The smaller the change in the ion source voltage data at a certain moment, the more stable the ion source voltage data is; and when the ion source voltage data and the vacuum degree of the mass spectrometer are more stable, and the internal environment of the mass spectrometer is closer to vacuum, the baseline deviation of the mass spectrum data of the drug solution will be less likely, and the operating stability of the mass spectrometer will be higher.

[0059] At this point, the mass spectrometer operation stability is obtained.

[0060] Step S003: Fit the mass spectrum data of the drug solution to obtain the mass spectrum curve of the drug solution, and divide the mass spectrum curve into several mass spectrum curve segments; obtain the ionization unevenness of each mass spectrum curve segment based on the similarity between each mass spectrum curve segment and its adjacent mass spectrum curve segment, combined with the distribution of all ions in each mass spectrum curve segment; obtain the interference degree of each ion based on the ionization unevenness of each mass spectrum curve segment corresponding to each ion, the mass spectrometer operation stability at each moment in the flight time period of each ion, and the high-frequency components in the mass spectrum curve segment corresponding to each ion, combined with the mass-to-charge ratio of each ion.

[0061] It should be noted that, since the time-of-flight mass spectrometry is highly sensitive to environmental changes, sample characteristics and instrument status; the detected mass spectrometry data has a baseline drift, which in turn causes the extracted spectral peak to be inaccurate, so it is necessary to remove the baseline drift in the mass spectrometry data to improve the accuracy of the extracted spectral peak. However, when removing the baseline drift in the mass spectrometry data by the traditional LMD local decomposition method, a local window needs to be set, and the data in the window is smoothed to extract the trend part of the data in the window and remove the baseline drift. However, when setting the local window, if the local window is too large, some low-frequency information in the window will be identified as part of the baseline drift and removed, resulting in the loss of part of the mass spectrometry information. If the local window is too small, the baseline drift information in the window cannot be effectively captured. Therefore, this embodiment proposes a method for extracting the time-of-flight mass spectrometry peak of drug detection, further combined with the mass spectrometer operation stability obtained in step S002, combined with the mass spectrometry data of the drug solution and the flight time period of the ions, the local window of each ion is adaptively produced, so as to achieve the removal of the baseline drift in the mass spectrometry data while avoiding the loss of mass spectrometry information.

[0062] It should be further explained that when collecting mass spectrometry data of a drug solution through a time-of-flight mass spectrometer, the drug solution needs to be ionized through an ion source. If the drug solution is ionized unevenly at this time, it will affect the stability of the baseline in the mass spectrometry data, thereby causing the baseline drift of the mass spectrometry data. Therefore, it is necessary to combine the uneven degree of drug ionization to better remove the baseline drift in the mass spectrometry data. Under normal circumstances, if the drug solution is ionized evenly, the peak shape in the mass spectrometry data always presents a high-pointed symmetrical shape; therefore, the mass spectrometry data can be divided into several segments, and by analyzing whether each segment conforms to the high-pointed symmetrical shape, it is evaluated whether the ionization of each segment is uniform; and because when some components in the drug solution are ionized unevenly, the component will be ionized into several ions with different mass-to-charge ratios, but since the several ions with different mass-to-charge ratios originate from the same component in the drug solution, the performance of several ions with different mass-to-charge ratios in the mass spectrometry data is similar, but because they are different ions, they will be divided into different segments, so if the ionization of a certain segment is uneven, the segment is not similar to the surrounding segments.

[0063] Preferably, in a specific embodiment of the present invention, the mass spectrum signal of the drug solution is curve-fitted using the least squares method to obtain a mass spectrum curve of the drug solution, all the minimum points in the mass spectrum curve are used as segmentation points, the mass spectrum curve is divided into a number of mass spectrum curve segments, and the mass-to-charge ratio corresponding to the maximum point in each mass spectrum curve segment is used as the target mass-to-charge ratio of each mass spectrum curve segment. Since the least squares method is a well-known prior art, it will not be described in detail in this embodiment;

[0064] For The mass spectrum curve segment will be The mass spectrum curve segment adjacent to the mass spectrum curve segment is recorded as The neighborhood curve segment of the mass spectrum curve segment; The mass spectrum segment and The target mass-to-charge ratio in the neighboring curve segments of the mass spectrum curve segment, combined with the The skewness, excess kurtosis and intensity of all ions of the mass spectrum curve segment are obtained. Since the skewness and excess kurtosis are known in the prior art, they will not be described in detail in this embodiment. The specific calculation formula for the ionization inhomogeneity of a mass spectrum curve segment is:

[0065]

[0066] In the formula, Indicates The degree of ionization inhomogeneity of each mass spectrum curve segment; Indicates The skewness of each mass spectrum segment; Indicates The excess kurtosis of each mass spectrum curve segment; Indicates The average intensity of all ions in a mass spectrum segment; Indicates The number of neighboring curve segments of a mass spectrum curve segment; Indicates The target mass-to-charge ratio in each mass spectrum segment; Indicates The ion mass corresponding to the target mass-to-charge ratio in each mass spectrum curve segment; Indicates The ion charge number corresponding to the target mass-to-charge ratio in each mass spectrum curve segment; Indicates The first segment of the mass spectrum The target mass-to-charge ratio in the neighborhood curve segments; Indicates The first segment of the mass spectrum The ion mass corresponding to the target mass-to-charge ratio in each neighborhood curve segment; Indicates The first segment of the mass spectrum The number of ion charges corresponding to the target mass-to-charge ratio in each neighborhood curve segment; Represents the absolute value function.

[0067] It should be noted that and They are the absolute value of skewness and excess kurtosis of the mass spectrum curve segment, and the larger the absolute value of skewness, the less centrally symmetrical the mass spectrum curve segment is, and the larger the excess kurtosis, the shorter and fatter the mass spectrum curve segment is. Indicates the similarity between the mass spectrum curve segment and the adjacent mass spectrum segment; when the mass spectrum curve segment is less centrally symmetrical and more short and fat, and the mass spectrum curve segment is more similar to the adjacent mass spectrum segment, the ionization of the mass spectrum curve segment is more uneven; when the ionization of the mass spectrum curve segment is uneven, the mass spectrum curve segment originally located in the same mass spectrum curve segment will be divided into two segments, and the intensity information of some descending ions will be lost, which will lead to the overall ion intensity of the mass spectrum curve segment being too high, such as Figure 2 As shown, Figure 2 This is a schematic diagram of the mass spectrum curve corresponding to uneven ionization; therefore The larger the value of , the more uneven the ionization of the mass spectrum curve segment.

[0068] It should be further explained that, during the flight of the time-of-flight mass spectrometer, the ions will be affected by the operating stability of the mass spectrometer. The lower the operating stability of the mass spectrometer during the flight time of the ions, the greater the degree of interference to the ions. Since the time-of-flight mass spectrometer will generate high-frequency noise during operation, which will affect the mass spectrometry data, it is also necessary to obtain the degree of interference to the ions based on its high-frequency components. Moreover, since ions with a small mass-to-charge ratio are more affected by the majority of high-frequency noise than ions with a large mass-to-charge ratio, when quantifying the degree of interference to the ions through the high-frequency components of the ions and the operating stability of the mass spectrometer during the flight time of the ions, it is necessary to further combine the mass-to-charge ratio of the ions to more accurately evaluate the degree of interference to the ions.

[0069] Preferably, in a specific embodiment of the present invention, for In the mass spectrum segment ions, for The mass spectrum curve segment is Fourier transformed to obtain the The spectrum of the mass spectrum curve segment is The amplitude and frequency in the spectrum diagram of the mass spectrum curve segment are obtained. High-frequency energy factor of each mass spectrum segment;

[0070] Furthermore, according to In the mass spectrum segment The stability of the mass spectrometer operation during the flight time of the ion, combined with the In the mass spectrum segment The mass-to-charge ratio of the ion is The high-frequency energy factor of the mass spectrum curve segment is obtained In the mass spectrum segment The specific calculation formula for the interference degree of an ion is:

[0071]

[0072] In the formula, Indicates In the mass spectrum curve segment The degree of interference of individual ions; Indicates The degree of ionization inhomogeneity of each mass spectrum curve segment; Indicates In the mass spectrum curve segment The mass-to-charge ratio of the ions; Indicates In the mass spectrum curve segment The mass of an ion; Indicates In the mass spectrum curve segment The number of ion charges; Indicates In the mass spectrum curve segment The number of moments in the flight time period of an ion; Indicates In the mass spectrum curve segment The flight time of the ion The mass spectrometer operation stability corresponding to each moment; represents the maximum normalization function; Indicates The amplitude of the maximum frequency in the spectrum of each mass spectrum curve segment; Indicates The maximum frequency in the spectrum of each mass spectrum segment; Indicates The high-frequency energy factor of each mass spectrum segment, Represents a linear normalization function, whose normalization range is all mass spectrum curve segments .

[0073] It should be noted that It indicates the stability of the mass spectrometer during the ion flight time period. The lower the stability of the mass spectrometer during the ion flight time period, the greater the degree of interference to the ion. It is the high-frequency energy factor of the mass spectrum curve segment, which represents the high-frequency component of the ion; It represents the mass-to-charge ratio of the ion. Since ions with a small mass-to-charge ratio are more affected by most high-frequency noise than ions with a large mass-to-charge ratio, a negatively correlated calculation weight is given to them through the mass-to-charge ratio of the ion. In addition, the more uneven the ionization of the mass spectrum curve segment is, the more serious the baseline drift interference will be to the mass spectrum data corresponding to the ions in the ion segment. Therefore The larger the value of In the mass spectrum segment The more interference there is on each ion, the greater the degree of interference there is.

[0074] At this point, the interference degree of each ion is obtained.

[0075] Step S004: According to the interference degree of each ion and the mass spectrum curve segment corresponding to each ion, the local window length of each ion is obtained; the mass spectrum data of the drug solution is decomposed according to the local window length of each ion, the baseline drift in the mass spectrum data of the drug solution is removed, and the mass spectrum peak is extracted.

[0076] It should be noted that after obtaining the interference degree of each ion in step S003, a local window of each ion can be adaptively generated according to the interference degree of each ion, thereby achieving the goal of removing the baseline drift in the mass spectrum data while avoiding the loss of mass spectrum information.

[0077] It should be further explained that, in the mass spectrometry data of the drug solution, there are a drug data part and a blank part, and the blank part indicates that there are no ions with a mass-to-charge ratio corresponding to the blank part in the drug solution; and usually the blank part can better reflect the hardness of the baseline drift suffered by the drug data part; therefore, in order to avoid the loss of mass spectrometry data when eliminating the baseline drift, the local window of the drug data should be appropriately increased or decreased in this embodiment; and the local window of the blank part should be appropriately increased.

[0078] Preferably, in a specific embodiment of the present invention, for any ion, the mass spectrum curve segment corresponding to the ion is used as the reference curve segment, and the local window length of the ion is obtained according to the mass-to-charge ratio in the reference curve segment and the length of the reference curve segment, combined with the interference degree of the ion, and the specific calculation formula is:

[0079]

[0080] In the formula, represents the local window length of the ion; Indicates the degree of interference of the ion; represents the definite integral of the reference curve segment; Indicates the length of the datum curve segment.

[0081] It should be noted that the degree of interference of the ion indicates that the more serious the baseline drift at the ion, the larger the local window should be given to remove the baseline drift; is the definite integral of the reference curve segment, which represents the peak area of ​​the reference curve segment. The larger the value of is, the more the reference curve segment has the characteristics of the drug data part, and vice versa, the more it has the characteristics of the blank data part; that is, The larger the value of , the smaller the local window should be, and vice versa.

[0082] It should be further explained that after the local window of each ion is adaptively generated, the mass spectrum data of the drug solution can be subjected to LDM decomposition according to the local window of each ion to remove the baseline drift in the mass spectrum data of the drug solution and extract the spectral peak of the mass spectrum data after the baseline drift is removed.

[0083] Specifically, the baseline drift in the drug solution is removed by the LDM decomposition method. When the baseline drift in the drug solution is removed by the LDM decomposition method, each local window length is the local window length of each ion. Since the LDM decomposition method is a well-known prior art, it will not be described in detail in this embodiment to obtain mass spectrum data of the drug solution with the baseline drift removed.

[0084] Furthermore, the spectral peaks of the mass spectral data of the drug solution with the baseline drift removed are extracted by mass spectral data processing software; the mass spectral data processing software includes but is not limited to: Mascot, SEQUEST and MaxQuant. Since the process of extracting spectral peaks by mass spectral data processing software is a well-known prior art, it will not be described in detail in this embodiment.

[0085] At this point, this embodiment is completed.

[0086] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for extracting time-of-flight mass spectrometry peaks for drug detection, characterized in that: The method comprises the following steps: Acquire ion source voltage data, mass spectrometer vacuum degree, ion flight time period, and mass spectrum data of drug solution; According to the ion source voltage data and the mass spectrometer vacuum degree at each moment, the operation stability of the mass spectrometer at each moment is obtained; Fitting the mass spectrum data of the drug solution to obtain the mass spectrum curve of the drug solution, and dividing the mass spectrum curve into a number of mass spectrum curve segments; obtaining the degree of ionization non-uniformity of each mass spectrum curve segment according to the degree of similarity between each mass spectrum curve segment and its adjacent mass spectrum curve segment, combined with the distribution of all ions in each mass spectrum curve segment; obtaining the degree of interference of each ion according to the degree of ionization non-uniformity of each mass spectrum curve segment corresponding to each ion, the mass spectrometer operation stability at each moment in the flight time period of each ion, and the high-frequency components in the mass spectrum curve segment corresponding to each ion, combined with the mass-to-charge ratio of each ion; According to the interference degree of each ion and the mass spectrum curve segment corresponding to each ion, the local window length of each ion is obtained; the mass spectrum data of the drug solution is decomposed according to the local window length of each ion, the baseline drift in the mass spectrum data of the drug solution is removed, and the mass spectrum peak is extracted.

2. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 1, characterized in that: The specific method of obtaining the ion source voltage data, the mass spectrometer vacuum degree, the ion flight time period and the mass spectrum data of the drug solution includes: The drug to be tested is dissolved in a solvent to obtain a sample solution, and the sample solution is filtered using a filter membrane to obtain a drug solution; mass spectrum data of the drug solution and the flight time period of each ion are obtained by a time-of-flight mass spectrometer; A voltage sensor is installed at the ion source, and a vacuum gauge is installed inside the time-of-flight mass spectrometer. In the process of obtaining mass spectrum data of a drug solution using the time-of-flight mass spectrometer, the ion source voltage data and the vacuum degree of the mass spectrometer are collected at each moment.

3. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 1, characterized in that: The specific method of obtaining the mass spectrometer operation stability at each moment according to the ion source voltage data and the mass spectrometer vacuum degree at each moment is as follows: For At this moment, As the center of the moment, build a The size of the neighborhood window is used as the The neighborhood window at the moment, is the preset neighborhood window size; The mass spectrometer vacuum degree in the neighborhood window at the moment is Fourier transformed to obtain The spectrum of the mass spectrometer vacuum degree in the neighborhood window at the moment is obtained, and the variance of all frequencies in the spectrum is obtained, which is recorded as Vacuum degree fluctuation factor at each moment; The ion source voltage data was fitted using the least squares method to obtain the ion source voltage curve. The derivative of the ion source voltage curve at the moment The vacuum fluctuation factor at the moment and the The vacuum degree of the mass spectrometer at the moment The stability of mass spectrometer operation at each moment.

4. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 3, characterized in that: The acquisition The specific calculation formula for the mass spectrometer operation stability at each moment is: In the formula, Indicates The operational stability of the mass spectrometer at each moment; Indicates The vacuum degree of the mass spectrometer at a certain moment; Indicates Vacuum degree fluctuation factor at each moment; Indicates The derivative of the ion source voltage curve at a certain moment; Represents the absolute value function.

5. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 1, characterized in that: The method of fitting the mass spectrum data of the drug solution to obtain a mass spectrum curve of the drug solution and dividing the mass spectrum curve into a plurality of mass spectrum curve segments includes: The mass spectrometry signal of the drug solution is curve fitted using the least squares method to obtain the mass spectrometry curve of the drug solution. All the minimum points in the mass spectrometry curve are used as segmentation points to divide the mass spectrometry curve into several mass spectrometry curve segments, and the mass-to-charge ratio corresponding to the maximum point in each mass spectrometry curve segment is used as the target mass-to-charge ratio of each mass spectrometry curve segment.

6. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 5, characterized in that: The method of obtaining the degree of ionization non-uniformity of each mass spectrum curve segment according to the degree of similarity between each mass spectrum curve segment and its adjacent mass spectrum curve segment and combining the distribution of all ions in each mass spectrum curve segment includes the following specific methods: For The mass spectrum curve segment will be The mass spectrum curve segment adjacent to the mass spectrum curve segment is recorded as The neighborhood curve segment of the mass spectrum curve segment; The mass spectrum segment The target mass-to-charge ratio in the neighboring curve segments of the mass spectrum curve segment, combined with the The skewness, excess kurtosis and intensity of all ions of the mass spectrum curve segment are obtained; The degree of ionization inhomogeneity of a mass spectrum curve segment.

7. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 6, characterized in that: The acquisition The ionization inhomogeneity of each mass spectrum curve segment includes the following specific calculation formula: In the formula, Indicates The degree of ionization inhomogeneity of each mass spectrum curve segment; Indicates The skewness of each mass spectrum segment; Indicates The excess kurtosis of each mass spectrum curve segment; Indicates The average intensity of all ions in a mass spectrum segment; Indicates The number of neighboring curve segments of a mass spectrum curve segment; Indicates The target mass-to-charge ratio in each mass spectrum segment; Indicates The ion mass corresponding to the target mass-to-charge ratio in each mass spectrum curve segment; Indicates The ion charge number corresponding to the target mass-to-charge ratio in each mass spectrum curve segment; Indicates The first segment of the mass spectrum The target mass-to-charge ratio in the neighborhood curve segments; Indicates The first segment of the mass spectrum The ion mass corresponding to the target mass-to-charge ratio in each neighborhood curve segment; Indicates The first segment of the mass spectrum The number of ion charges corresponding to the target mass-to-charge ratio in each neighborhood curve segment; Represents the absolute value function.

8. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 1, characterized in that: The specific method of obtaining the interference degree of each ion includes: For In the mass spectrum curve segment ions, for The mass spectrum curve segment is Fourier transformed to obtain the The spectrum of the mass spectrum curve segment is The amplitude and frequency in the spectrum diagram of the mass spectrum curve segment are obtained. High-frequency energy factor of each mass spectrum segment; According to In the mass spectrum curve segment The stability of the mass spectrometer operation during the flight time of the ion, combined with the In the mass spectrum curve segment The mass-to-charge ratio of the ion is The high-frequency energy factor of the mass spectrum curve segment is obtained In the mass spectrum curve segment The degree of interference of an ion.

9. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 8, characterized in that: The acquisition In the mass spectrum curve segment The specific calculation formula for the interference degree of each ion is as follows: In the formula, Indicates In the mass spectrum curve segment The degree of interference of individual ions; Indicates The degree of ionization inhomogeneity of each mass spectrum curve segment; Indicates In the mass spectrum curve segment The mass-to-charge ratio of the ions; Indicates In the mass spectrum curve segment The mass of an ion; Indicates In the mass spectrum curve segment The number of ion charges; Indicates In the mass spectrum curve segment The number of moments in the flight time period of an ion; Indicates In the mass spectrum curve segment The flight time of the ion The mass spectrometer operation stability corresponding to each moment; represents the maximum normalization function; Indicates The amplitude of the maximum frequency in the spectrum of each mass spectrum curve segment; Indicates The maximum frequency in the spectrum of each mass spectrum segment; Indicates The high-frequency energy factor of each mass spectrum segment, represents the linear normalization function.

10. The method for extracting peaks of a time-of-flight mass spectrometer for drug detection according to claim 1, characterized in that: The method of obtaining the local window length of each ion according to the interference degree of each ion and the mass spectrum curve segment corresponding to each ion includes the following specific methods: For any ion, the mass spectrum curve segment corresponding to the ion is used as the reference curve segment. According to the mass-to-charge ratio in the reference curve segment and the length of the reference curve segment, combined with the interference degree of the ion, the local window length of the ion is obtained. The specific calculation formula is: In the formula, represents the local window length of the ion; Indicates the degree of interference of the ion; represents the definite integral of the reference curve segment; Indicates the length of the datum curve segment.

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