Intelligent detection system for pharmaceutical production quality

Abstract

The application provides an intelligent detection system for drug production quality, and relates to the technical field of drug quality detection. The system comprises a drug sample acquisition module for acquiring a chiral drug sample to be detected and determining a stereoisomer list; a parameter optimization module for optimizing chromatographic control parameters according to the stereoisomer list and generating a stereoisomer retention time list; a chromatographic column effluent acquisition and chromatographic spectrum generation module for separating the sample and generating a chromatographic spectrum; a spectrum partitioning and ratio parameter calculation module for processing the spectrum and calculating enantiomer parameters; and a drug identification module for judging drug quality according to parameter threshold values and performing corresponding identification. The application can solve the problem that the prior art relies on experience to set chromatographic control parameters, which leads to insufficient parameter stability and affects the accuracy and reliability of chiral drug chromatographic analysis, improve the accuracy of spectrum analysis and parameter calculation, strengthen drug quality control and identification, and improve detection precision and sensitivity.

Description

Technical Field

[0001] This application relates to the field of drug quality inspection technology, and in particular to an intelligent detection system for drug production quality. Background Technology

[0002] Traditional drug manufacturing quality testing methods often rely on manual operation and experience-based judgment, resulting in low efficiency and susceptibility to human factors. With continuous technological advancements and expanding applications, intelligent testing methods will play an increasingly important role in drug manufacturing quality control.

[0003] Currently, existing technologies rely on experience to set chromatographic control parameters, resulting in insufficient parameter stability. This affects the accuracy and reliability of chiral drug chromatographic analysis, ultimately causing adverse effects on the research, development, production, and quality control of chiral drugs. Summary of the Invention

[0004] The purpose of this application is to provide an intelligent detection system for drug production quality, which solves the problem that existing technologies rely on experience to set chromatographic control parameters, resulting in insufficient parameter stability and thus affecting the accuracy and reliability of chiral drug chromatographic analysis.

[0005] In view of the above problems, this application provides an intelligent detection system for drug production quality.

[0006] This application provides an intelligent detection system for drug production quality. The intelligent detection system for drug production quality includes: a drug sample acquisition module for sampling a chiral drug to be tested, obtaining a chiral drug sample, wherein the chiral drug sample has a stereoisomer list; a parameter optimization module for optimizing chromatographic control parameters according to the stereoisomer list, obtaining desired control parameters for the gas chromatograph, gas flow meter, and detector, wherein the stereoisomer list has a stereoisomer retention time list under the constraints of the desired control parameters for the gas chromatograph, the gas flow meter, and the detector; and a column effluent acquisition module for injecting the chiral drug sample into the gas chromatograph inlet, and, based on the... The gas chromatograph separates the column effluent using the desired control parameters of the gas chromatograph and the gas flow meter. A chromatogram generation module detects the column effluent according to the desired control parameters of the detector and generates a detection chromatogram. A chromatogram partitioning module partitions the detection chromatogram based on the stereoisomer retention time list to obtain a chromatogram peak image list, wherein the peak image list corresponds one-to-one with the stereoisomer list. A ratio parameter calculation module calculates the enantiomeric excess parameter and enantiomeric ratio parameter based on the peak image list. A drug labeling module identifies the target chiral drug as unsuitable when the enantiomeric excess parameter does not meet the enantiomeric excess threshold range or / and the enantiomeric ratio parameter does not meet the enantiomeric ratio threshold range.

[0007] One or more technical solutions provided in this application have at least the following technical effects or advantages: The drug sample acquisition module is used to sample the chiral drug to be tested, obtaining a chiral drug sample, wherein the chiral drug sample has a stereoisomer list; the parameter optimization module is used to optimize the chromatographic control parameters according to the stereoisomer list, obtaining the expected control parameters for the gas chromatograph, the gas flow meter, and the detector, wherein the stereoisomer list has a stereoisomer retention time list under the constraints of the expected control parameters for the gas chromatograph, the gas flow meter, and the detector; the column effluent acquisition module is used to inject the chiral drug sample from the gas chromatograph inlet, and obtain the column effluent by separation according to the expected control parameters for the gas chromatograph and the gas flow meter; the chromatogram generation module is used to optimize the column effluent according to the expected control parameters for the detector. The system performs detection on the analytes and generates a detection chromatogram. A chromatogram partitioning module partitions the detected chromatogram based on the stereoisomer retention time list to obtain a list of chromatographic peak images, where each peak image corresponds one-to-one with the stereoisomer list. A ratio parameter calculation module calculates the enantiomeric excess parameter and enantiomeric ratio parameter based on the chromatographic peak image list. A drug labeling module identifies the chiral drug being tested when the enantiomeric excess parameter does not meet the enantiomeric excess threshold range or / and the enantiomeric ratio parameter does not meet the enantiomeric ratio threshold range. This effectively solves the problem of insufficient parameter stability caused by relying on experience to set chromatographic control parameters in existing technologies, which affects the accuracy and reliability of chiral drug chromatographic analysis. It improves the accuracy of chromatogram interpretation and parameter calculation, strengthens drug quality control and labeling, and enhances detection precision and sensitivity.

[0008] The above description is merely an overview of the technical solution of this application. To better understand the technical means of this application and to facilitate its implementation according to the description, and to make the above and other objects, features, and advantages of this application more apparent, specific embodiments of this application are described below. It should be understood that the content described in this section is not intended to identify key or important features of the embodiments of this application, nor is it intended to limit the scope of this application. Other features of this application will become readily apparent through the following description. Attached Figure Description

[0009] To more clearly illustrate the technical solutions in this application 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 merely exemplary. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0010] Figure 1This is a schematic diagram of the structure of an intelligent detection system for drug production quality according to this application; Figure 2 This is a schematic diagram of the process for obtaining multiple sets of chiral drugs to be tested in an intelligent detection system for drug production quality according to this application.

[0011] Explanation of reference numerals in the attached figures: Drug sample acquisition module 11, parameter optimization module 12, column effluent acquisition module 13, chromatogram generation module 14, chromatogram partitioning module 15, ratio parameter calculation module 16, and drug identification module 17. Detailed Implementation

[0012] This application provides an intelligent detection system for drug production quality, which solves the problem that existing technologies rely on experience to set chromatographic control parameters, resulting in insufficient parameter stability and affecting the accuracy and reliability of chiral drug chromatographic analysis. It improves the accuracy of chromatographic interpretation and parameter calculation, strengthens drug quality control and labeling, and enhances detection precision and sensitivity.

[0013] The technical solutions of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. It should be understood that this application is not limited to the exemplary embodiments described herein. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application. It should also be noted that, for ease of description, only the parts related to this application are shown in the accompanying drawings, not all of them.

[0014] This application provides an intelligent detection system for drug production quality; please refer to the appendix. Figure 1 The intelligent detection system for drug production quality includes: The drug sample acquisition module 11 is used to sample the chiral drug to be tested and obtain a chiral drug sample, wherein the chiral drug sample has a list of stereoisomers.

[0015] Specifically, chiral drugs refer to drug molecules with a chiral center. A stereoisomer list provides information on all possible stereoisomers of the chiral drug being tested, including structural characteristics and relative abundance. Based on the drug's characteristics, prepare clean, uncontaminated sampling tools, such as sampling needles, sampling spoons, and sampling bottles. Before sampling, check that the chiral drug's packaging is intact and leak-free. Choose a suitable sampling location based on the characteristics of the drug packaging and storage container, avoiding sampling from the bottom or edge of the container to reduce contamination and error. Use the prepared sampling tools and follow the prescribed sampling method. During sampling, avoid direct hand contact with the drug sample to minimize contamination. Quickly transfer the extracted sample to a clean sampling bottle and seal it immediately. Select appropriate storage conditions, such as temperature, humidity, and light exposure, based on the drug's characteristics.

[0016] The parameter optimization module 12 is used to optimize the chromatographic control parameters according to the stereoisomer list to obtain the expected control parameters of the gas chromatograph, the expected control parameters of the gas flow meter, and the expected control parameters of the detector. The stereoisomer list has a stereoisomer retention time list under the constraints of the expected control parameters of the gas chromatograph, the expected control parameters of the gas flow meter, and the expected control parameters of the detector.

[0017] Specifically, the stereoisomer list provides information on all possible stereoisomers of the chiral drug being tested, including their structural characteristics and relative abundance. Based on the properties of the stereoisomers, such as polarity and volatility, a suitable chromatographic column is selected to ensure effective separation. Adjusting the column temperature affects the retention time of the stereoisomers on the column, leading to better separation. The carrier gas flow rate affects the migration speed of the stereoisomers on the column and needs to be adjusted for optimal separation. Precise control of the carrier and auxiliary gas flow rates ensures the stability of the chromatographic system and the separation effect. A suitable detector, such as a thermal conductivity detector or an electron capture detector, is selected based on the properties of the stereoisomers. Adjusting the detector's sensitivity, response time, and other parameters ensures accurate detection of the stereoisomers. Under optimized chromatographic control parameters, a retention time list for the stereoisomers is generated through simulation, providing the retention time of each stereoisomer under specific chromatographic conditions.

[0018] The column effluent acquisition module 13 is used to inject the chiral drug sample from the gas chromatograph inlet and obtain the column effluent by separation according to the desired control parameters of the gas chromatograph and the desired control parameters of the gas flow meter.

[0019] Specifically, ensure the gas chromatograph is in good working order, with all components, such as the column, detector, and gas flow meter, correctly installed and connected. Check the stability of the carrier gas and auxiliary gas supply and adjust them to the desired flow rates. Input the optimized gas chromatograph control parameters, such as column temperature and carrier gas rate, into the gas chromatograph control system. Set the desired control parameters for the gas flow meter to ensure accurate gas metering and a stable supply. The sample can be diluted or dissolved using an appropriate solvent. Accurately inject the chiral drug sample into the gas chromatograph inlet using a syringe. The injected sample, carried by the carrier gas, enters the column, initiating the separation process. According to the set chromatographic control parameters, stereoisomers are retained and migrated to varying degrees on the column, thus achieving separation. The separated stereoisomers elute sequentially from the column, forming the column effluent.

[0020] The chromatogram generation module 14 is used to detect the effluent from the chromatographic column according to the desired control parameters of the detector and generate a detection chromatogram.

[0021] Specifically, based on the properties of the chiral drug sample and its stereoisomers, a suitable detector is selected, including thermal conductivity detectors, electron capture detectors, and flame ionization detectors. The optimized desired detector control parameters are input into the gas chromatograph's detector control system, including detector sensitivity, response time, and temperature. The column effluent, carried by the carrier gas, enters the detector. The detector sensitively detects the stereoisomers in the effluent and converts them into measurable electrical signals. The detector output signal is amplified and processed, and the amplified and processed signal is acquired in real time and converted into a digital signal. The acquired data, including time and signal intensity, is used to generate a chromatogram. The chromatogram displays the relationship between time and signal intensity.

[0022] The chromatogram partitioning module 15 is used to partition the detected chromatogram based on the stereoisomer retention time list to obtain a chromatogram peak image list, wherein the chromatogram peak image list corresponds one-to-one with the stereoisomer list.

[0023] Specifically, the stereoisomer retention time list provides retention time information for each stereoisomer under specific chromatographic conditions. The quality of the chromatogram is checked, including baseline stability and signal-to-noise levels, and then the chromatogram is corrected, including time correction and signal intensity correction, to eliminate potential errors. Based on the stereoisomer retention time list, the approximate location of the chromatographic peak corresponding to each stereoisomer is determined on the chromatogram, and a reasonable partition range is set for each stereoisomer. On the detected chromatogram, partitioning is performed according to the determined partition range. Partitioning tools in chromatography data processing software can be used, or partition boundaries can be manually marked on the chromatogram. Within each partition, the corresponding chromatographic peak is identified; a chromatographic peak is the signal peak formed on the detector after the stereoisomer is separated on the chromatographic column. The image of each identified chromatographic peak is extracted from the detected chromatogram to form an independent list of chromatographic peak images. Each chromatographic peak image should correspond one-to-one with a stereoisomer in the stereoisomer list.

[0024] The ratio parameter calculation module 16 is used to calculate the enantiomeric excess parameter and the enantiomeric ratio parameter based on the list of chromatographic peak images.

[0025] Specifically, peak area analysis is performed on each chromatographic peak image, measuring the peak areas corresponding to the target stereoisomer and the undesirable stereoisomer. Based on the peak areas of the target and undesirable stereoisomers, an enantiomeric excess parameter is calculated, reflecting the degree of excess of the target stereoisomer relative to the undesirable stereoisomer. An enantiomeric ratio parameter, i.e., the ratio of the peak area of ​​the target stereoisomer to the peak area of ​​the undesirable stereoisomer, is also calculated. The drug identification module 17 is used to identify the chiral drug to be tested as defective when the enantiomeric excess parameter does not meet the enantiomeric excess threshold range or / and the enantiomeric ratio parameter does not meet the enantiomeric ratio threshold range.

[0026] Specifically, based on drug quality standards, as well as the clinical efficacy and safety of the drug, those skilled in the art set enantiomeric ratio threshold ranges and enantiomeric excess threshold ranges. The calculated enantiomeric excess parameter is compared with the set enantiomeric excess threshold range; if it is not within the set threshold range, it is determined that the requirement is not met. Similarly, the calculated enantiomeric ratio parameter is compared with the set enantiomeric ratio threshold range; if it is not within the set threshold range, it is also determined that the requirement is not met. If the enantiomeric excess parameter and / or enantiomeric ratio parameter of the chiral drug being tested does not meet the set threshold range, it needs to be labeled as unacceptable. This includes clearly marking "unacceptable" or "unacceptable" on the sample vial or analysis record.

[0027] Furthermore, the drug sample acquisition module 11 is also used for: The chiral drug to be tested includes N chiral drugs; N sets of production control parameters for the N chiral drugs to be tested are extracted from the production monitoring database; based on the N sets of production control parameters, the N chiral drugs to be tested are classified to obtain multiple sets of chiral drugs to be tested; samples are taken from the multiple sets of chiral drugs to obtain multiple sets of chiral drug samples, wherein the chiral drug samples belong to the multiple sets of chiral drug samples.

[0028] Specifically, the system connects to a production monitoring database containing production control parameters for the chiral drugs to be tested. N sets of production control parameters for N chiral drugs to be tested are extracted from the database, including raw material ratios, reaction temperatures, reaction times, catalyst types and amounts, etc. Classification criteria are determined based on the nature and importance of the production control parameters. For example, classification can be based on different ranges of raw material ratios, reaction temperatures, or different catalyst types. The selected classification criteria are used to group the N chiral drugs to be tested. Drugs with similar production control parameters are grouped together to ensure more representative subsequent sampling and analysis. Based on the classification results, a detailed sampling plan is developed, including the number of samples to be taken from each group of chiral drugs, the sampling method, and the sampling time. According to the sampling plan, samples are taken from multiple groups of chiral drugs to obtain multiple sets of chiral drug samples. Each set of samples should represent the drugs in its respective category. Each set of chiral drug samples is uniquely identified to facilitate accurate tracking of its origin and classification information in subsequent analysis and recording.

[0029] Furthermore, such as Figure 2 As shown, the drug sample acquisition module is also used for: Separate the N sets of production control parameters to obtain a first set of production control parameters and a second set of production control parameters; obtain a set of production control attributes, wherein the set of production control attributes has a set of main control attributes; configure a set of production control deviation thresholds for the set of production control attributes through a user terminal; classify the N chiral drugs to be tested based on the set of production control deviation thresholds and the set of main control attributes to obtain the multiple sets of chiral drugs to be tested.

[0030] Specifically, N sets of production control parameters are extracted from the production monitoring database. Two sets of production control parameters are separated and designated as the first set and the second set, respectively. A set of production control attributes is defined, containing all production control parameters that may affect the quality of chiral drugs. Through the user interface, a set of production control deviation thresholds for the production control attribute set can be configured, defining the acceptable deviation range for each production control attribute. Deviations exceeding these thresholds indicate anomalies in the production process, requiring more stringent inspection or classification of the corresponding drugs. Based on the set of production control deviation thresholds and the set of main control attributes, the N chiral drugs to be tested are classified. By comparing the production control parameters of each drug with the thresholds in the set of main control attributes, drugs with similar deviation ranges are grouped together.

[0031] Furthermore, the drug sample acquisition module 11 is also used for: If the deviation of any major control attribute parameter of the first set of production control parameters and the second set of production control parameters does not meet the production control deviation threshold set, the first and second chiral drugs to be tested are classified into different categories. If the deviation of each major control attribute parameter of the first and second sets of production control parameters meets the production control deviation threshold set, the proportion of attributes in the first and second sets of production control parameters that meet the production control deviation threshold set is calculated and set as a classification parameter. If the classification parameter is greater than or equal to the classification parameter threshold, the first and second chiral drugs to be tested are classified into the same category. If the classification parameter is less than the classification parameter threshold, the first and second chiral drugs to be tested are classified into different categories.

[0032] Specifically, a first set of production control parameters and a second set of production control parameters are extracted from the production monitoring database. These two sets of parameters correspond to the first and second chiral drugs to be tested, respectively. The main control attributes in the production control attribute set are determined, and a set of production control deviation thresholds for these main control attributes is configured through the user terminal. These thresholds define the acceptable deviation range. If the deviation of any main control attribute parameter in either the first or second set of production control parameters does not meet the production control deviation threshold set, then the first and second chiral drugs to be tested are classified into different categories. If the deviation of every main control attribute parameter in both sets of production control parameters meets the production control deviation threshold set, then the next statistical step is performed. The proportion of attributes in the first and second sets of production control parameters that meet the production control deviation threshold set is calculated; this is the classification parameter. If the classification parameter is greater than or equal to the classification parameter threshold, it indicates that the two sets of production control parameters are very similar in their main control attributes; therefore, the first and second chiral drugs to be tested are classified into the same category. If the classification parameter is less than the classification parameter threshold, it indicates that there is a difference in the main control attributes between the two groups of production control parameters. Therefore, the first and second chiral drugs to be tested are classified into different categories.

[0033] Furthermore, the drug sample acquisition module 11 is also used for: Using the first production control attribute of the production control attribute set as the sole independent variable and the drug property characteristic value as the dependent variable, production log data of the chiral drug to be tested is collected. The production log data includes recorded values ​​of the first production control attribute and detected drug property values. The normalized data of the first production control attribute recorded values ​​are sorted from smallest to largest to obtain a first data sequence. The normalized data of the drug property detected values ​​are sorted according to the first data sequence to obtain a second data sequence. A feature curve is constructed using the first data sequence as the x-axis and the second data sequence as the y-axis. The mode slope of the feature curve is calculated and set as the first production control attribute correlation degree. When the first production control attribute correlation degree is greater than or equal to a correlation degree threshold, the first production control attribute is added to the main control attribute set.

[0034] Specifically, production log data of the chiral drug to be tested is collected from the production monitoring database, including the recorded values ​​of the first production control attribute and the corresponding drug property test values. The recorded values ​​of the first production control attribute and the drug property test values ​​are normalized to eliminate the influence of different dimensions on data analysis. The normalized first production control attribute recorded values ​​are arranged in ascending order to obtain the first data sequence. Simultaneously, the normalized drug property test values ​​are arranged in the order of the first data sequence to obtain the second data sequence. A feature curve is constructed in a two-dimensional coordinate system with the first data sequence as the x-axis and the second data sequence as the y-axis, which can intuitively show the relationship between the first production control attribute and the drug property characteristic values. By calculating the slope between each point on the feature curve and counting the slope value that appears most frequently, this is taken as the correlation degree of the first production control attribute, reflecting the degree of influence of the first production control attribute on the drug property characteristic values. The correlation degree of the first production control attribute is compared with a preset correlation degree threshold. If the correlation degree is greater than or equal to the correlation degree threshold, it indicates that the first production control attribute has a significant impact on the drug property characteristic values, and it is added to the main control attribute set.

[0035] Furthermore, the parameter optimization module 12 is also used for: Randomly configure the control parameters of the first gas chromatograph, the first gas flow meter, and the first detector; traverse the stereoisomer list and collect a retention time list of the first stereoisomers under the constraints of the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters; calculate the retention time deviation of the first stereoisomer retention time list to obtain the minimum retention time deviation; when the minimum retention time deviation is greater than or equal to the retention time deviation threshold, set the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters as the desired control parameters of the gas chromatograph, the gas flow meter, and the detector, and set the first stereoisomer retention time list as the stereoisomer retention time list; otherwise, update the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters.

[0036] Specifically, the control parameters of the first gas chromatograph, including temperature, pressure, and flow rate, are randomly configured, as are the control parameters of the first gas flow meter, to ensure accurate gas measurement. The control parameters of the first detector are also randomly configured to facilitate accurate detection of the presence of stereoisomers. The list of stereoisomers to be tested is traversed, and each stereoisomer needs to be detected on the gas chromatograph. Under the set control parameters of the first gas chromatograph, the first gas flow meter, and the first detector, the retention time of each stereoisomer is collected, forming a first stereoisomer retention time list. Retention time deviation is calculated on the first stereoisomer retention time list, i.e., the difference between the actual retention time and the expected retention time for each stereoisomer is compared. The minimum retention time deviation is found from all calculated deviations, reflecting the accuracy of stereoisomer separation under the current control parameters. The minimum retention time deviation is compared with a preset retention time deviation threshold. If the minimum retention time deviation is greater than or equal to the retention time deviation threshold, it indicates that the current control parameters can meet the requirements for accurate separation and detection of stereoisomers. At this point, the control parameters of the first gas chromatograph, the first gas flow meter, and the first detector are set to the desired control parameters, and the first stereoisomer retention time list is set to the final stereoisomer retention time list. If the minimum retention time deviation is less than the retention time deviation threshold, it indicates that the current control parameters need further optimization. In this case, the control parameters of the first gas chromatograph, the first gas flow meter, and the first detector are updated, and the above steps are repeated until a set of control parameters that meets the requirements is found.

[0037] Furthermore, the parameter optimization module 12 is also used for: The stereoisomer list is traversed, and several sets of stereoisomer retention times are collected under the constraints of the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters. The mean value analysis of the several sets of stereoisomer retention times is performed to obtain several first stereoisomer retention times, and a first stereoisomer retention time list is constructed.

[0038] Specifically, information for each stereoisomer is obtained one by one from the list of stereoisomers. The control parameters of the gas chromatograph, gas flow meter, and detector are set to the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters, respectively. Under these set control parameters, each stereoisomer is detected by gas chromatography, and the retention time of each stereoisomer during the detection process is recorded, forming several sets of stereoisomer retention time data. The collected stereoisomer retention time data are grouped according to the stereoisomer. The mean of the data in each group is calculated to obtain the first retention time of each stereoisomer, representing the average retention time of that stereoisomer under the set control parameters. The calculated first retention times of each stereoisomer are compiled into a list, i.e., the first stereoisomer retention time list, which includes the average retention time of each stereoisomer under the set control parameters.

[0039] Furthermore, the ratio parameter calculation module 16 is used for: Based on the chromatographic peak image list, target stereoisomers and undesirable stereoisomers of the first chiral center are extracted, up to the target stereoisomer and undesirable stereoisomer of the Mth chiral center; peak area analysis is performed based on the chromatographic peak image list to obtain the enantiomer excess parameter and enantiomer ratio parameter of the first chiral center; peak area analysis is performed based on the chromatographic peak image list to obtain the enantiomer excess parameter and enantiomer ratio parameter of the Mth chiral center; the enantiomer excess parameter and enantiomer ratio parameter of the first chiral center, up to the enantiomer excess parameter and enantiomer ratio parameter of the Mth chiral center, are added to the enantiomer excess parameter and the enantiomer ratio parameter.

[0040] Specifically, each image in the chromatographic peak image list is examined one by one. Using image processing techniques such as peak detection and shape recognition, the target stereoisomer and undesirable stereoisomer of the chiral center are extracted from each image. This extraction process is repeated for each image in the chromatographic peak image list until all target and undesirable stereoisomers from the first chiral center to the Mth chiral center are obtained. Peak area analysis is performed on each chromatographic peak image to measure the peak area corresponding to the target and undesirable stereoisomers. Based on the peak areas of the target and undesirable stereoisomers, the enantiomeric excess parameter of the first chiral center is calculated, reflecting the degree of excess of the target stereoisomer relative to the undesirable stereoisomer. The enantiomeric ratio parameter of the first chiral center is calculated, which is the ratio of the peak area of ​​the target stereoisomer to the peak area of ​​the undesirable stereoisomer. The peak area analysis and parameter calculation steps are repeated to obtain the enantiomeric excess parameter and ratio parameter of the Mth chiral center. The calculated enantiomeric excess parameters and ratio parameters from the first to the Mth chiral centers are then compiled. These parameters are added to the enantiomeric excess parameter list and the enantiomeric ratio parameter list. Key information can be extracted from the chromatographic peak image list, and the enantiomeric excess parameter and enantiomeric ratio parameter can be calculated, providing an important basis for the quality and purity assessment of chiral drugs.

[0041] The above description of the disclosed embodiments enables those skilled in the art to make or use this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

[0042] Obviously, those skilled in the art can make various modifications and variations to this application without departing from the spirit and scope of this application. Therefore, if such modifications and variations fall within the scope of this application and its equivalents, this application also intends to include such modifications and variations.

Claims

1. An intelligent detection system for drug production quality, characterized in that, include: A drug sample acquisition module is used to sample the chiral drug to be tested and obtain a chiral drug sample, wherein the chiral drug sample has a list of stereoisomers; The parameter optimization module is used to optimize the chromatographic control parameters according to the stereoisomer list to obtain the expected control parameters of the gas chromatograph, the expected control parameters of the gas flow meter, and the expected control parameters of the detector. The stereoisomer list has a stereoisomer retention time list under the constraints of the expected control parameters of the gas chromatograph, the expected control parameters of the gas flow meter, and the expected control parameters of the detector. The column effluent acquisition module is used to inject the chiral drug sample from the gas chromatograph inlet and obtain the column effluent by separation according to the desired control parameters of the gas chromatograph and the desired control parameters of the gas flow meter. The chromatogram generation module is used to detect the effluent from the chromatographic column according to the desired control parameters of the detector and generate a detection chromatogram. The chromatogram partitioning module is used to partition the detected chromatogram based on the stereoisomer retention time list to obtain a chromatogram peak image list, wherein the chromatogram peak image list corresponds one-to-one with the stereoisomer list; The ratio parameter calculation module is used to calculate the enantiomeric excess parameter and the enantiomeric ratio parameter based on the list of chromatographic peak images. The drug identification module is used to identify the chiral drug to be tested as defective when the enantiomeric excess parameter does not meet the enantiomeric excess threshold range or / and the enantiomeric ratio parameter does not meet the enantiomeric ratio threshold range. The parameter optimization module is also used for: Randomly configure the control parameters of the first gas chromatograph, the first gas flow meter, and the first detector; Traverse the list of stereoisomers and collect a list of the retention times of the first stereoisomers under the constraints of the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters. The retention time deviation of the first stereoisomer retention time list is calculated to obtain the minimum retention time deviation. When the minimum retention time deviation is greater than or equal to the retention time deviation threshold, the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters are set as the expected control parameters of the gas chromatograph, the expected control parameters of the gas flow meter, and the expected control parameters of the detector, and the first stereoisomer retention time list is set as the stereoisomer retention time list. Otherwise, update the control parameters of the first gas chromatograph, the first gas flow meter, and the first detector; The ratio parameter calculation module is also used for: Based on the list of chromatographic peak images, extract the target stereoisomer with the first chiral center and the undesirable stereoisomer with the first chiral center, until the target stereoisomer with the Mth chiral center and the undesirable stereoisomer with the Mth chiral center; Peak area analysis was performed based on the chromatographic peak image list to obtain the first chiral center enantiomeric excess parameter and the first chiral center enantiomeric ratio parameter. Peak area analysis was performed based on the list of chromatographic peak images to obtain the enantiomeric excess parameter and the enantiomeric ratio parameter of the Mth chiral center. The first chiral center enantiomer excess parameter and the first chiral center enantiomer ratio parameter, up to the Mth chiral center enantiomer excess parameter and the Mth chiral center enantiomer ratio parameter, are added to the enantiomer excess parameter and the enantiomer ratio parameter.

2. The intelligent detection system for drug production quality as described in claim 1, characterized in that, The drug sample acquisition module is also used for: The chiral drug to be tested includes N chiral drugs; Extract N sets of production control parameters for the N chiral drugs to be tested from the production monitoring database; Based on the N sets of production control parameters, the N chiral drugs to be tested are classified to obtain multiple sets of chiral drugs to be tested; Sampling is performed on the multiple groups of chiral drugs to be tested to obtain multiple groups of chiral drug samples, wherein the chiral drug samples belong to the multiple groups of chiral drug samples.

3. The intelligent detection system for drug production quality as described in claim 2, characterized in that, The drug sample acquisition module is also used for: Separate the N sets of production control parameters to obtain the first set of production control parameters and the second set of production control parameters; Obtain a set of production control attributes, wherein the set of production control attributes has a set of main control attributes; Configure the production control deviation threshold set of the production control attribute set through the user terminal; Based on the set of production control deviation thresholds and the set of main control attributes, the N chiral drugs to be tested are classified to obtain the multiple groups of chiral drugs to be tested.

4. The intelligent detection system for drug production quality as described in claim 3, characterized in that, The drug sample acquisition module is also used for: If the deviation of any one of the main control attribute parameters of the first set of production control parameters and the second set of production control parameters does not meet the production control deviation threshold set, the first chiral drug to be tested and the second chiral drug to be tested are classified into different categories. When the deviation of each major control attribute parameter of the first group of production control parameters and the second group of production control parameters satisfies the production control deviation threshold set, the proportion of attributes that satisfy the production control deviation threshold set in the first group of production control parameters and the second group of production control parameters is counted and set as a classification parameter. When the classification parameter is greater than or equal to the classification parameter threshold, the first chiral drug to be tested and the second chiral drug to be tested are classified into the same class. When the classification parameter is less than the classification parameter threshold, the first chiral drug to be tested and the second chiral drug to be tested are classified into different categories.

5. The intelligent detection system for drug production quality as described in claim 3, characterized in that, The drug sample acquisition module is also used for: Using the first production control attribute of the production control attribute set as the sole independent variable and the drug property characteristic value as the dependent variable, production log data of the chiral drug to be tested is collected, wherein the production log data has the first production control attribute record value and the drug property detection value; The normalized data of the first production control attribute record values ​​are sorted from smallest to smallest to obtain the first data sequence; The normalized data of the drug property detection values ​​are arranged according to the first data sequence to obtain the second data sequence; A feature curve is constructed using the first data sequence as the x-axis data and the second data sequence as the y-axis data; The mode slope value of the characteristic curve is calculated and set as the correlation degree of the first production control attribute; When the correlation degree of the first production control attribute is greater than or equal to the correlation degree threshold, the first production control attribute is added to the main control attribute set.

6. The intelligent detection system for drug production quality as described in claim 1, characterized in that, The parameter optimization module is also used for: Traverse the list of stereoisomers and collect several sets of stereoisomer retention times under the constraints of the first gas chromatograph control parameters, the first gas flow meter control parameters, and the first detector control parameters. By iterating through the retention times of the several groups of stereoisomers and performing a mean analysis of the central points, several retention times of the first stereoisomers are obtained, and a list of retention times of the first stereoisomers is constructed.

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