Radiopharmaceutical component detection method and system

Abstract

The invention relates to the technical field of chromatography separation, in particular to a radiopharmaceutical component detection method and system.The method comprises the steps that a standard characteristic wave band and a standard spectrum absorptivity wave band corresponding to each substance contained in a to-be-detected radiopharmaceutical are obtained, acquiring an ultraviolet spectrum image of the to-be-detected radiopharmaceutical at each current moment in the current gradient elution process; determining the spectral absorption correlation of each substance at each current moment; screening out a target substance from the to-be-detected radiopharmaceutical, and determining an overall interference influence factor of the target substance at each current moment; determining a current adjustment coefficient corresponding to the target substance; adjusting the current mobile phase proportion according to the current adjustment coefficient; based on the adjusted mobile phase proportion, separating the target substance from the to-be-detected radiopharmaceutical through gradient elution, and detecting the content of the target substance. According to the invention, the efficiency of detecting the medicine component content of the radiopharmaceutical is improved.

Description

Technical Field

[0001] This invention relates to the field of chromatographic separation technology, and specifically to a method and system for detecting radiopharmaceutical components. Background Technology

[0002] With the rapid development of medical imaging technology, radiopharmaceuticals are playing an increasingly important role in fields such as tumor diagnosis and targeted therapy. These drugs target tissues by labeling them with specific radionuclides, achieving precise localization or treatment of lesions, and have become an important tool in modern precision medicine. Common radiopharmaceuticals include fluorine-18 labeled drugs used in positron emission tomography (PET) and drugs such as technetium-99 and radium-223 used for treatment.

[0003] In the preparation and quality control of radiopharmaceuticals, accurate detection of drug components is a crucial step in ensuring their safety and efficacy. High-performance liquid chromatography (HPLC) is a commonly used technique for separating and analyzing radiopharmaceutical components. By separating drug components of different polarities with a specific mobile phase, and combining this with a radioactive detector or ultraviolet detector, radioactive components and their metabolites can be effectively distinguished and quantified. However, the special properties of radiopharmaceuticals, such as their short half-life and time-sensitive activity requirements, pose significant challenges to traditional detection methods.

[0004] High-performance liquid chromatography (HPLC) often employs a fixed mobile phase gradient for elution in the determination of drug components. However, when using a fixed mobile phase gradient to determine the content of drug components in radiopharmaceuticals, the following technical problems frequently arise: During isocratic elution of radiopharmaceuticals, the chromatographic peaks of the components that elute later become wider. Furthermore, since the proportion of the mobile phase remains constant, isocratic elution of radiopharmaceuticals usually requires a long time to complete the analysis, resulting in poor efficiency in separating drug components and consequently poor efficiency in detecting the content of drug components in radiopharmaceuticals. Summary of the Invention

[0005] To address the technical problem of poor efficiency in detecting the content of drug components in radiopharmaceuticals due to the poor efficiency of drug component separation, this invention proposes a method and system for detecting radiopharmaceutical components.

[0006] In a first aspect, the present invention provides a method for detecting radiopharmaceutical components, the method comprising: Obtain the standard characteristic band and standard spectral absorbance band corresponding to each substance contained in the radiopharmaceutical to be detected, and obtain the ultraviolet spectral image at each current moment during the current gradient elution process of the radiopharmaceutical to be detected. Based on the standard spectral absorbance bands corresponding to each substance, and the spectral absorbance corresponding to the wavelengths of the standard characteristic bands of the same substance in the ultraviolet spectral image at each current moment, determine the spectral absorption correlation of each substance at each current moment. Substances to be detected in the radiopharmaceuticals are selected as target substances. Based on the overlap between the standard characteristic bands of the target substances and other substances, and the spectral absorption correlation between the target substances and other substances at each current time, the overall interference factor of the target substances at each current time is determined. Based on the spectral absorption correlation and overall interference factor of the target substance at all current times, determine the current adjustment coefficient corresponding to the target substance; Adjust the current flow phase ratio based on the current adjustment factor corresponding to the target substance; Based on the adjusted mobile phase ratio, the target substance is separated from the radiopharmaceutical to be tested by gradient elution, and the content of the target substance is detected.

[0007] In conjunction with the first aspect above, in one possible implementation, obtaining the standard characteristic band and standard spectral absorbance band corresponding to each substance contained in the radiopharmaceutical to be detected includes: Any one of the substances contained in the radiopharmaceutical to be tested is identified as a labeled substance, and the pure substance corresponding to the labeled substance is identified as a labeled pure substance; Obtain the ultraviolet spectral image corresponding to the labeled pure substance as the labeled ultraviolet spectral image, and determine any characteristic peak in the labeled ultraviolet spectral image as the labeled characteristic peak; Wavelengths with spectral absorbance less than or equal to a preset absorbance are selected from the labeled ultraviolet spectral images and used as labeled wavelengths, wherein the preset absorbance is equal to a preset percentage of the spectral absorbance corresponding to the labeled characteristic peak. On both sides of the wavelength corresponding to the marked feature peak, a marker wavelength closest to the wavelength corresponding to the marked feature peak is selected as an endpoint to form the target wavelength segment corresponding to the marked feature peak. The union of the target wavelength bands corresponding to all characteristic peaks in the labeled ultraviolet spectrum image is determined as the standard characteristic wavelength band corresponding to the labeled substance; The standard spectral absorbance band corresponding to the labeled substance is formed by taking all the spectral absorbance values ​​in the labeled ultraviolet spectral image that correspond to wavelengths belonging to the standard characteristic bands of the labeled substance.

[0008] In conjunction with the first aspect above, in one possible implementation, determining the spectral absorption correlation of each substance at each current moment based on the standard spectral absorbance band corresponding to each substance and the spectral absorbance corresponding to the wavelengths of the standard characteristic bands belonging to the same substance in the ultraviolet spectral image at each current moment includes: Any one of the substances contained in the radiopharmaceutical to be tested is identified as the marker substance, and any current moment is identified as the marker moment; The spectral absorbance of all wavelengths belonging to the standard characteristic bands corresponding to the labeled substance in the ultraviolet spectral image at the labeled time constitutes the current spectral absorbance band of the labeled substance at the labeled time. The Pearson correlation coefficient between the standard spectral absorbance band corresponding to the labeled substance and its current spectral absorbance band at the labeling time is normalized to obtain the spectral absorption correlation of the labeled substance at the labeling time.

[0009] In conjunction with the first aspect above, in one possible implementation, determining the overall interference factor of the target substance at each current moment based on the overlap between the standard characteristic bands corresponding to the target substance and other substances, and the spectral absorption correlation between the target substance and other substances at each current moment, includes: Each substance other than the target substance among all the substances contained in the radiopharmaceutical to be tested is designated as a reference substance; The intersection between the standard characteristic band corresponding to the target substance and the standard characteristic band corresponding to each reference substance is determined as the target intersection between the target substance and each reference substance. Based on the number of wavelengths within the target intersection between the target substance and each reference substance, and the spectral absorption correlation between the target substance and each reference substance at each current time, the reference interference coefficient of each reference substance for the target substance at each current time is determined. The average of the reference interference coefficients of all reference materials to the target material at each current time is determined as the overall interference influence factor of the target material at each current time.

[0010] In conjunction with the first aspect mentioned above, in one possible implementation, the formula corresponding to the reference interference coefficient of the reference material to the target material at the current moment is: ;in, It is in the At the current moment, the first The reference interference coefficient of a reference material to the target material; It is the sequence number of the current moment in the current gradient elution process; It is the reference material number; Is the target substance and the first The number of wavelengths within the target intersection between different reference materials; The target substance is in the first Spectral absorption correlation at the current moment; It is the first The reference material in the first The spectral absorption correlation at the current moment.

[0011] In conjunction with the first aspect above, in one possible implementation, determining the current adjustment coefficient corresponding to the target substance based on the spectral absorption correlation and overall interference factor of the target substance at all current times includes: Based on the spectral absorption correlation and overall interference factor of the target substance at each current moment, the initial adjustment factor of the target substance at each current moment is determined; The mean of the initial adjustment factors of the target substance at all current times is determined as the current adjustment coefficient corresponding to the target substance.

[0012] In conjunction with the first aspect mentioned above, in one possible implementation, the formula corresponding to the initial adjustment factor of the target substance at the current moment is: ;in, The target substance is in the first The initial adjustment factor at the current moment; It is the sequence number of the current moment in the current gradient elution process; It is a natural exponential function; The target substance is in the first Spectral absorption correlation at the current moment; It is a pre-set correlation threshold; The target substance is in the first The overall disturbance impact factor at the current moment.

[0013] In conjunction with the first aspect above, in one possible implementation, adjusting the current flow phase ratio based on the current adjustment coefficient corresponding to the target substance includes: Based on the current adjustment coefficient, the current proportion of mobile phase A and the current proportion of mobile phase B are adjusted to obtain the corrected proportion of mobile phase A and the corrected proportion of mobile phase B, wherein the ratio of the current proportion of mobile phase A to the current proportion of mobile phase B represents the current proportion of mobile phase. The ratio of the corrected proportion of mobile phase A to the corrected proportion of mobile phase B is determined as the adjusted mobile phase proportion.

[0014] In conjunction with the first aspect mentioned above, in one possible implementation, the formulas corresponding to the corrected proportions of mobile phase A and mobile phase B are as follows: ; ;in, It corrects the proportion of mobile phase A; It corrects the proportion of mobile phase B; This represents the current percentage of mobile phase A. This represents the current percentage of mobile phase B. This is the current adjustment factor; It is the initial adjustment change ratio obtained in advance.

[0015] Secondly, the present invention provides a radiopharmaceutical component detection system, the system comprising: The data acquisition module is used to acquire the standard characteristic band and standard spectral absorbance band corresponding to each substance contained in the radiopharmaceutical to be detected, and to acquire the ultraviolet spectral image of the radiopharmaceutical to be detected at each current moment during the current gradient elution process. The correlation determination module is used to determine the spectral absorption correlation of each substance at each current moment based on the standard spectral absorption band corresponding to each substance and the spectral absorption of the wavelength corresponding to the standard characteristic band of the same substance in the ultraviolet spectral image at each current moment. The interference effect quantification module is used to screen out substances to be detected from the radiopharmaceutical to be tested as target substances, and to determine the overall interference effect factor of the target substance at each current time based on the overlap between the standard characteristic bands of the target substance and other substances, and the spectral absorption correlation between the target substance and other substances at each current time. The adjustment coefficient determination module is used to determine the current adjustment coefficient of the target substance based on the spectral absorption correlation and overall interference factor of the target substance at all current times. The mobile phase ratio adjustment module is used to adjust the current mobile phase ratio according to the current adjustment coefficient corresponding to the target substance. The elution detection module is used to separate the target substance from the radiopharmaceutical to be tested by gradient elution based on the adjusted mobile phase ratio, and to detect the content of the target substance.

[0016] Thirdly, a server is provided, including a memory and a processor. The memory is used to store executable program code, and the processor is used to call and run the executable program code from the memory, causing the device to perform the methods of the first aspect or any possible implementation thereof.

[0017] Fourthly, a computer program product is provided, comprising: computer program code, which, when run on a computer, causes the computer to perform the methods described in the first aspect or any possible implementation thereof.

[0018] Fifthly, a computer-readable storage medium is provided that stores computer program code, which, when executed on a computer, causes the computer to perform the methods described in the first aspect or any possible implementation thereof.

[0019] The present invention has the following beneficial effects: This invention provides a method for detecting radiopharmaceutical components, solving the technical problem of poor efficiency in detecting the content of radiopharmaceutical components and improving the efficiency of this method. Compared to methods using a fixed mobile phase gradient, this invention comprehensively considers multiple characteristics related to mobile phase ratio adjustment during the detection process, such as spectral absorption correlation, overall interference factors, and the current adjustment coefficient. This adaptively adjusts the mobile phase ratio, ensuring that the peak shapes of components eluting first or later are generally sharp and symmetrical, and also reducing the separation time of drug components to a certain extent, thereby improving the efficiency of detecting the content of radiopharmaceutical components. Attached Figure Description

[0020] To more clearly illustrate the technical solutions and advantages in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a flowchart of a method for detecting radiopharmaceutical components according to the present invention; Figure 2 This is a schematic diagram of the gradient elution process of the present invention; Figure 3 This is a schematic diagram of the composition and structure of a radiopharmaceutical component detection system according to the present invention; Figure 4 This is a schematic diagram of the structure of a computer device according to the present invention. Detailed Implementation

[0022] To further illustrate the technical means and effects adopted by the present invention to achieve its intended purpose, the specific implementation methods, structures, features, and effects of the technical solution proposed according to the present invention are described in detail below with reference to the accompanying drawings and preferred embodiments. In the following description, different "one embodiment" or "another embodiment" do not necessarily refer to the same embodiment. Furthermore, specific features, structures, or characteristics in one or more embodiments can be combined in any suitable form.

[0023] Unless otherwise defined, 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 pertains.

[0024] refer to Figure 1 The flowchart illustrates some embodiments of a method for detecting radiopharmaceutical components according to the present invention. This method for detecting radiopharmaceutical components includes the following steps: Step S1: Obtain the standard characteristic band and standard spectral absorbance band corresponding to each substance contained in the radiopharmaceutical to be detected, and obtain the ultraviolet spectral image at each current moment during the current gradient elution process of the radiopharmaceutical to be detected.

[0025] The radiopharmaceutical to be detected can be any drug whose content of drug components is to be determined. The substance contained in the drug is its drug component. Drug components can be, but are not limited to, fluorine-18, technetium-99, and radium-223. The standard characteristic band corresponding to the substance can be a data segment consisting of all wavelengths in the ultraviolet spectrum image of the pure substance. The pure substance can represent an object containing only that substance. The standard spectral absorbance band corresponding to the substance can be a data segment consisting of all spectral absorbances in the ultraviolet spectrum image of the pure substance. The horizontal axis of the ultraviolet spectrum image represents wavelength, and the vertical axis represents spectral absorbance. In gradient elution, elution is often performed under multiple mobile phase gradients. The mobile phase gradient can be the ratio of mobile phase A and mobile phase B over time during liquid chromatography. Each gradient elution process can represent the elution process performed under each mobile phase gradient. During gradient elution, the duration of different gradient elution processes can be the same, and its duration can be 5 seconds. The current gradient elution process can be the most recent gradient elution process. The current gradient elution process can be a complete elution process under a mobile phase gradient. The start time of the current gradient elution process can be the end time of the previous gradient elution process. The current time can also be the moment used to acquire the ultraviolet spectral image during the current gradient elution process. The gradient elution process can be as follows: Figure 2 As shown.

[0026] As an example, this step may include the following steps: The first step is to identify any one of the substances contained in the radiopharmaceutical to be tested as the labeling substance, and to identify the pure substance corresponding to the labeling substance as the labeled pure substance.

[0027] The second step is to obtain the ultraviolet spectral image corresponding to the above-mentioned labeled pure substance, and use it as the labeled ultraviolet spectral image. Any characteristic peak in the above-mentioned labeled ultraviolet spectral image is then identified as the labeled characteristic peak.

[0028] The third step is to select wavelengths with spectral absorbance less than or equal to a preset absorbance from the above-mentioned labeled ultraviolet spectral images as labeled wavelengths.

[0029] The preset absorbance can be equal to a preset percentage of the spectral absorbance corresponding to the marked characteristic peaks. This preset percentage can be a pre-set ratio. For example, the preset percentage could be 20%.

[0030] The fourth step is to select a marker wavelength that is closest to the wavelength corresponding to the marker feature peak on both sides of the wavelength on both sides of the wavelength on both sides of the wavelength on both sides of the marker feature peak, and use it as an endpoint to form the target wavelength segment corresponding to the marker feature peak.

[0031] Among them, the two endpoints of the target wavelength band corresponding to the marker feature peak can be one on each side of the wavelength corresponding to the marker feature peak, and the marker wavelength closest to the wavelength corresponding to the marker feature peak.

[0032] The fifth step is to determine the standard characteristic band corresponding to the labeled substance by taking the union of the target wavelength bands corresponding to all characteristic peaks in the above-mentioned labeled ultraviolet spectral images.

[0033] The sixth step is to construct the standard spectral absorbance band corresponding to the labeled substance by taking all the spectral absorbance values ​​in the above-mentioned labeled ultraviolet spectral image whose wavelengths belong to the standard characteristic band of the labeled substance.

[0034] Among them, the wavelengths corresponding to all spectral absorbance in the standard spectral absorbance bands of the labeled substance in the labeled ultraviolet spectral image all belong to the standard characteristic bands of the labeled substance.

[0035] It should be noted that obtaining the standard characteristic band and standard spectral absorption band corresponding to a substance can facilitate subsequent determination of whether the substance has been separated.

[0036] Step 7: Using an ultraviolet-visible light detector, acquire the ultraviolet spectral image of the radiopharmaceutical being tested at each current moment during the current gradient elution process.

[0037] Step S2: Based on the standard spectral absorbance band corresponding to each substance and the spectral absorbance corresponding to the wavelength of the standard characteristic band corresponding to the same substance in the ultraviolet spectral image at each current moment, determine the spectral absorption correlation of each substance at each current moment.

[0038] As an example, this step may include the following steps: The first step is to identify any one of the substances contained in the radiopharmaceutical to be tested as the marker substance, and to identify any current time as the marker time.

[0039] The second step is to construct the current spectral absorption band of the labeled substance at the above-mentioned labeling time by taking the spectral absorbance of all wavelengths belonging to the standard characteristic bands of the ultraviolet spectrum image at the above-mentioned labeling time.

[0040] The third step is to normalize the Pearson correlation coefficient between the standard spectral absorbance band corresponding to the above-mentioned labeled substance and its current spectral absorbance band at the above-mentioned labeling time, so as to obtain the spectral absorption correlation of the above-mentioned labeled substance at the above-mentioned labeling time.

[0041] It should be noted that the greater the spectral absorption correlation of the labeled substance at the labeling time, the more similar the standard spectral absorbance band corresponding to the labeled substance is to its current spectral absorbance band at the labeling time, and the more likely the labeled substance is to be separated at the labeling time.

[0042] Step S3: Select the substances to be tested from the radiopharmaceuticals and use them as target substances. Based on the overlap between the standard characteristic bands of the target substances and other substances, and the spectral absorption correlation between the target substances and other substances at each current time, determine the overall interference factor of the target substances at each current time.

[0043] The target substance can be a radiopharmaceutical component whose content needs to be measured.

[0044] As an example, this step may include the following steps: The first step is to identify each other substance in the radiopharmaceutical to be tested, excluding the target substance, as a reference substance.

[0045] The second step is to determine the intersection between the standard characteristic bands corresponding to the target material and the standard characteristic bands corresponding to each reference material as the target intersection between the target material and each reference material.

[0046] The third step is to determine the reference interference coefficient of each reference material to the target material at each current moment, based on the number of wavelengths within the target intersection between the target material and each reference material, and the spectral absorption correlation between the target material and each reference material at each current moment.

[0047] For example, the formula for determining the reference interference coefficient of the reference material to the target material at the current moment can be: ;in, It is in the At the current moment, the first The reference interference coefficient of a reference material to the target material. It is the sequence number of the current moment in the current gradient elution process. It is the reference material number. Is the target substance and the first The number of wavelengths within the target intersection between different reference materials. The target substance is in the first The spectral absorption correlation at the current moment. It is the first The reference material in the first The spectral absorption correlation at the current moment.

[0048] It should be noted that if different substances appear simultaneously in an ultraviolet spectral image at the same time, it often indicates that these substances interfere with each other to some extent. The larger the value, the more likely it is to indicate that the target substance is similar to the first... The more wavelengths that overlap between two reference materials, the stronger the correlation between the target material and the second reference material. The more likely there is interference between the reference materials, the more likely the spectral absorbance at the overlapping wavelengths in the ultraviolet spectrum image will not match that of the target material or the first reference material. A reference material. When The smaller the size, the more likely it is to be in the first... At the current moment, the first The less similar the current spectral absorbance bands of the reference and target materials are to their respective standard spectral absorbance bands, the more likely this dissimilarity is due to overlapping wavelengths, and thus, the more likely interference exists between them. Therefore, when The larger the value, the more likely it is to indicate that the target substance is similar to the first... The more likely there is interference between different reference materials.

[0049] The fourth step is to determine the average value of the reference interference coefficients of all reference materials to the target material at each current moment as the overall interference influence factor of the target material at each current moment.

[0050] Step S4: Determine the current adjustment coefficient corresponding to the target substance based on the spectral absorption correlation and overall interference factor of the target substance at all current times.

[0051] As an example, this step may include the following steps: The first step is to determine the initial adjustment factor of the target substance at each current moment based on the spectral absorption correlation and overall interference factor of the target substance at each current moment.

[0052] For example, the formula for determining the initial adjustment factor of the target substance at the current moment can be: ;in, The target substance is in the first The initial adjustment factor at the current moment. It is the sequence number of the current moment in the current gradient elution process. It is a natural exponential function. The target substance is in the first The spectral absorption correlation at the current moment. It is a pre-set correlation threshold, which can be 0.9. The target substance is in the first The overall disturbance impact factor at the current moment.

[0053] It should be noted that when The larger the value, the more likely it is that the target substance is in the first stage of its life cycle. The greater the spectral absorption correlation at the current moment, the more likely the target substance is to be at the first... The better the separation at the current moment, the less adjustment of the mobile phase ratio is needed. The smaller the value, the more likely it is that the target substance is in the first stage of its life cycle. The less likely the current flow is to be disturbed by other substances, the less adjustment of the mobile phase ratio is usually needed. Therefore, when The bigger and The smaller, The smaller, and at this time A value less than or equal to 1 usually indicates that adjusting the mobile phase ratio is less necessary. smaller and When it is larger, The relatively larger, and at this time Often greater than 1, it often indicates that the target substance is in the [missing information - likely a number or value]. The less obvious the separation performance at the current moment, and the greater the influence of impurities on the target substance, the more it indicates that the mobile phase ratio should be adjusted to accelerate the separation of the target substance.

[0054] The second step is to determine the mean of the initial adjustment factors of the target substance at all current times as the current adjustment coefficient corresponding to the target substance.

[0055] Step S5: Adjust the current mobile phase ratio according to the current adjustment coefficient corresponding to the target substance.

[0056] As an example, this step may include the following steps: The first step is to adjust the current proportion of mobile phase A and the current proportion of mobile phase B according to the above adjustment coefficients to obtain the corrected proportion of mobile phase A and the corrected proportion of mobile phase B.

[0057] Here, the current mobile phase A percentage can be the proportion of mobile phase A in the current gradient elution process. The current mobile phase B percentage can be the proportion of mobile phase B in the current gradient elution process. The ratio of the current mobile phase A percentage to the current mobile phase B percentage can represent the current mobile phase proportion.

[0058] It should be noted that when starting gradient elution, a higher proportion of mobile phase A and a lower proportion of mobile phase B are often set. Then, the proportion of mobile phase B is gradually increased while the proportion of mobile phase A is decreased. For example, if mobile phase A is water and mobile phase B is acetonitrile, then initially 90% water and 10% acetonitrile can be set, at which point the proportion of mobile phase A is 90% and the proportion of mobile phase B is 10%.

[0059] For example, the formulas for determining the proportions of modified mobile phase A and modified mobile phase B can be: ; ;in, It corrects the proportion of mobile phase A. It corrects the proportion of mobile phase B. This represents the current percentage of mobile phase A. This represents the current percentage of mobile phase B. This is the current adjustment factor. This is the pre-obtained initial adjustment change ratio. The initial adjustment change ratio can be a pre-set amount of change in the mobile phase proportion. In practice, when starting gradient elution, the proportion of mobile phase B is often gradually increased while the proportion of mobile phase A is decreased, thus adjusting the mobile phase proportion. For example, if mobile phase A is water and mobile phase B is acetonitrile, then initially it can be set to 90% water and 10% acetonitrile. After eluting with 90% water and 10% acetonitrile for 5 seconds (one gradient elution cycle), the proportions of water and acetonitrile can be set to 89% and 11% respectively, at which point the initial adjustment change ratio is 1%.

[0060] The second step is to determine the adjusted mobile phase ratio by comparing the ratio of corrected mobile phase A to corrected mobile phase B.

[0061] Step S6: Based on the adjusted mobile phase ratio, the target substance is separated from the radiopharmaceutical to be tested by gradient elution, and the content of the target substance is detected.

[0062] It should be noted that elution can be performed based on the currently adjusted mobile phase ratio. After reaching the duration corresponding to one gradient elution process, the ultraviolet spectral images of the radiopharmaceutical to be detected at each moment in the new gradient elution process can be obtained. Steps S2-S5 are then repeated, eluting based on the newly adjusted mobile phase ratio, and after reaching the duration corresponding to one gradient elution process, the above steps are repeated until the target substance is separated from the radiopharmaceutical to be detected. Compared with existing gradient elution methods, the improvement of this embodiment mainly lies in achieving adaptive adjustment of the mobile phase ratio in each gradient elution process.

[0063] As an example, spectral data, including peak area and retention time, can be recorded in real time at every moment. Peak area is used as a representative of the target substance concentration, and data processing is typically performed using spectral analysis software. Next, a standard curve is established using standard solutions of known concentrations. The relationship between peak area and concentration is obtained through linear regression analysis, and the equation of the standard curve is calculated. Then, the peak area of ​​the target substance in the real-time spectral data is substituted into the standard curve equation to solve for its corresponding concentration. To ensure the accuracy of the results, the internal standard method can be used. By adding an internal standard substance of known concentration, the peak area of ​​the target substance in the sample is adjusted to eliminate the influence of instrument drift and environmental factors. Here, the sample represents the radiopharmaceutical to be detected. Finally, the calculated target substance concentration is combined with the sample volume to obtain the content information of the target substance in the sample. Through precise data analysis and comparison, the reliability and accuracy of the results are ensured.

[0064] refer to Figure 3 Based on the same inventive concept as the above-described method embodiments, this invention provides a radiopharmaceutical component detection system. This system includes a memory, a processor, and a computer program stored in the memory and executable on the processor. When executed by the processor, the computer program implements the steps of a radiopharmaceutical component detection method, specifically including: The data acquisition module 301 is used to acquire the standard characteristic band and standard spectral absorption band corresponding to each substance contained in the radiopharmaceutical to be detected, and to acquire the ultraviolet spectral image at each current moment during the current gradient elution process of the radiopharmaceutical to be detected. The correlation determination module 302 is used to determine the spectral absorption correlation of each substance at each current moment based on the standard spectral absorption band corresponding to each substance and the spectral absorption rate corresponding to the wavelength of the standard characteristic band corresponding to the same substance in the ultraviolet spectral image at each current moment. Interference effect quantification module 303 is used to screen out substances to be detected from the radiopharmaceutical to be tested as target substances, and to determine the overall interference effect factor of the target substance at each current time based on the overlap between the standard characteristic bands of the target substance and other substances, and the spectral absorption correlation between the target substance and other substances at each current time. The adjustment coefficient determination module 304 is used to determine the current adjustment coefficient of the target substance based on the spectral absorption correlation and overall interference influence factor of the target substance at all current times. The mobile phase ratio adjustment module 305 is used to adjust the current mobile phase ratio according to the current adjustment coefficient corresponding to the target substance; The elution detection module 306 is used to separate the target substance from the radiopharmaceutical to be tested by gradient elution based on the adjusted mobile phase ratio, and to detect the content of the target substance.

[0065] Figure 4 This is a schematic diagram of the structure of a computer device provided in an embodiment of the present invention. For example, as shown... Figure 4 As shown, the computer device 400 includes: a memory 401, a processor 402, and a computer program 403 stored in the memory 401 and running on the processor 402, wherein when the processor 402 executes the computer program 403, the computer device can perform any of the radiopharmaceutical component detection methods described above.

[0066] Based on the same inventive concept as the above-described method embodiments, the present invention provides a server, including a memory and a processor. The memory is used to store executable program code, and the processor is used to call and run the executable program code from the memory, causing the device to perform any of the above-described radiopharmaceutical component detection methods.

[0067] Based on the same inventive concept as the above-described method embodiments, the present invention provides a computer program product comprising: computer program code, which, when run on a computer, causes the computer to execute any of the above-described methods for detecting radiopharmaceutical components.

[0068] Based on the same inventive concept as the above-described method embodiments, the present invention provides a computer-readable storage medium storing computer program code, which, when executed on a computer, causes the computer to perform any of the above-described methods for detecting radiopharmaceutical components.

[0069] In summary, compared to methods using a fixed mobile phase gradient for detecting the content of drug components in radiopharmaceuticals, this invention comprehensively considers multiple characteristics related to mobile phase ratio adjustment during the detection process, such as spectral absorption correlation, overall interference factors, and the current adjustment coefficient. This adaptively adjusts the mobile phase ratio, ensuring that the peak shapes of components eluting first or later are generally sharp and symmetrical. Furthermore, it reduces the separation time of drug components to a certain extent, thereby improving the efficiency of detecting the content of drug components in radiopharmaceuticals.

[0070] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention, and should all be included within the protection scope of the present invention.

Claims

1. A method for detecting radiopharmaceutical components, characterized in that, Includes the following steps: Obtain the standard characteristic band and standard spectral absorbance band corresponding to each substance contained in the radiopharmaceutical to be tested, and obtain the ultraviolet spectral image at each current moment during the current gradient elution process of the radiopharmaceutical to be tested; Based on the standard spectral absorbance bands corresponding to each substance, and the spectral absorbance corresponding to the wavelengths of the standard characteristic bands of the same substance in the ultraviolet spectral image at each current moment, determine the spectral absorption correlation of each substance at each current moment. Substances to be detected in the radiopharmaceuticals are selected as target substances. Based on the overlap between the standard characteristic bands of the target substances and other substances, and the spectral absorption correlation between the target substances and other substances at each current time, the overall interference factor of the target substances at each current time is determined. Based on the spectral absorption correlation and overall interference factor of the target substance at all current times, determine the current adjustment coefficient corresponding to the target substance; Adjust the current flow phase ratio based on the current adjustment factor corresponding to the target substance; Based on the adjusted mobile phase ratio, the target substance is separated from the radiopharmaceutical to be tested by gradient elution, and the content of the target substance is detected.

2. The method for detecting radiopharmaceutical components according to claim 1, characterized in that, The acquisition of the standard characteristic band and standard spectral absorbance band corresponding to each substance contained in the radiopharmaceutical to be detected includes: Any one of the substances contained in the radiopharmaceutical to be tested is identified as a labeled substance, and the pure substance corresponding to the labeled substance is identified as a labeled pure substance; Obtain the ultraviolet spectral image corresponding to the labeled pure substance as the labeled ultraviolet spectral image, and determine any characteristic peak in the labeled ultraviolet spectral image as the labeled characteristic peak; Wavelengths with spectral absorbance less than or equal to a preset absorbance are selected from the labeled ultraviolet spectral images and used as labeled wavelengths, wherein the preset absorbance is equal to a preset percentage of the spectral absorbance corresponding to the labeled characteristic peak. On both sides of the wavelength corresponding to the marked feature peak, a marker wavelength closest to the wavelength corresponding to the marked feature peak is selected as an endpoint to form the target wavelength segment corresponding to the marked feature peak. The union of the target wavelength bands corresponding to all characteristic peaks in the labeled ultraviolet spectrum image is determined as the standard characteristic wavelength band corresponding to the labeled substance; The standard spectral absorbance band corresponding to the labeled substance is formed by taking all the spectral absorbance values ​​in the labeled ultraviolet spectral image that correspond to wavelengths belonging to the standard characteristic bands of the labeled substance.

3. The method for detecting radiopharmaceutical components according to claim 1, characterized in that, The determination of the spectral absorption correlation of each substance at each current moment, based on the standard spectral absorbance band corresponding to each substance and the spectral absorbance corresponding to the wavelength of the standard characteristic band corresponding to the same substance in the ultraviolet spectral image at each current moment, includes: Any one of the substances contained in the radiopharmaceutical to be tested is identified as the marker substance, and any current moment is identified as the marker moment; The spectral absorbance of all wavelengths belonging to the standard characteristic bands corresponding to the labeled substance in the ultraviolet spectral image at the labeled time constitutes the current spectral absorbance band of the labeled substance at the labeled time. The Pearson correlation coefficient between the standard spectral absorbance band corresponding to the labeled substance and its current spectral absorbance band at the labeling time is normalized to obtain the spectral absorbance correlation of the labeled substance at the labeling time.

4. The method for detecting radiopharmaceutical components according to claim 1, characterized in that, The determination of the overall interference factor of the target substance at each current moment, based on the overlap between the standard characteristic bands corresponding to the target substance and other substances, and the spectral absorption correlation between the target substance and other substances at each current moment, includes: Each substance other than the target substance among all the substances contained in the radiopharmaceutical to be tested is designated as a reference substance; The intersection between the standard characteristic band corresponding to the target substance and the standard characteristic band corresponding to each reference substance is determined as the target intersection between the target substance and each reference substance. Based on the number of wavelengths within the target intersection between the target substance and each reference substance, and the spectral absorption correlation between the target substance and each reference substance at each current time, the reference interference coefficient of each reference substance for the target substance at each current time is determined. The average of the reference interference coefficients of all reference materials to the target material at each current time is determined as the overall interference influence factor of the target material at each current time.

5. The method for detecting radiopharmaceutical components according to claim 4, characterized in that, The formula for the reference interference coefficient of the reference material to the target material at the current moment is: ;in, It is in the At the current moment, the first The reference interference coefficient of a reference material to the target material; It is the sequence number of the current moment in the current gradient elution process; It is the reference material number; Is the target substance and the first The number of wavelengths within the target intersection between different reference materials; The target substance is in the first Spectral absorption correlation at the current moment; It is the first The reference material in the first The spectral absorption correlation at the current moment.

6. The method for detecting radiopharmaceutical components according to claim 1, characterized in that, The process of determining the current adjustment coefficient for the target substance based on the spectral absorption correlation and overall interference factor at all current times includes: Based on the spectral absorption correlation and overall interference factor of the target substance at each current moment, determine the initial adjustment factor of the target substance at each current moment; The mean of the initial adjustment factors of the target substance at all current times is determined as the current adjustment coefficient corresponding to the target substance.

7. The method for detecting radiopharmaceutical components according to claim 6, characterized in that, The formula for the initial adjustment factor of the target substance at the current moment is: ;in, The target substance is in the first The initial adjustment factor at the current moment; It is the sequence number of the current moment in the current gradient elution process; It is the natural exponential function; The target substance is in the first Spectral absorption correlation at the current moment; It is a pre-set correlation threshold; The target substance is in the first The overall disturbance impact factor at the current moment.

8. The method for detecting radiopharmaceutical components according to claim 1, characterized in that, The step of adjusting the current mobile phase ratio based on the current adjustment coefficient corresponding to the target substance includes: Based on the current adjustment coefficient, the current proportion of mobile phase A and the current proportion of mobile phase B are adjusted to obtain the corrected proportion of mobile phase A and the corrected proportion of mobile phase B, wherein the ratio of the current proportion of mobile phase A to the current proportion of mobile phase B represents the current proportion of mobile phase. The ratio of the corrected proportion of mobile phase A to the corrected proportion of mobile phase B is determined as the adjusted mobile phase proportion.

9. The method for detecting radiopharmaceutical components according to claim 8, characterized in that, The formulas for correcting the proportion of mobile phase A and correcting the proportion of mobile phase B are as follows: ； ;in, It corrects the proportion of mobile phase A; It corrects the proportion of mobile phase B; This represents the current percentage of mobile phase A. This represents the current percentage of mobile phase B. This is the current adjustment factor; It is the initial adjustment change ratio obtained in advance.

10. A system for detecting radiopharmaceutical components, characterized in that, It includes a processor and a memory, the processor being used to process instructions stored in the memory to implement a method for detecting radiopharmaceutical components according to any one of claims 1-9.

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