An analytical and detection method for polymyxin B sulfate

Abstract

The present invention belongs to the technical field of analysis and detection of polymyxin B sulfate. The present invention provides an analysis and detection method for polymyxin B sulfate. During the historical detection period, the historical column efficiency values are recorded when the chromatographic column analyzes and detects polymyxin B sulfate multiple times, and trend change analysis is carried out to judge whether the column efficiency decreases. If the overall column efficiency shows a downward trend during the historical detection period, the change trend types of multiple column efficiency values are identified, and according to the identified change trend types, the predicted column life loss degree is obtained, as well as the current column efficiency value of the current chromatographic column for analyzing and detecting polymyxin B sulfate. The current column efficiency value is divided by the predicted column life loss degree to obtain the predicted remaining column life value, which solves the problem that the service life of the chromatographic column cannot be accurately known in the analysis and detection of polymyxin B sulfate.

Description

Technical Field

[0001] The present invention belongs to the technical field of analysis and detection of polymyxin B sulfate, and specifically relates to an analysis and detection method for polymyxin B sulfate. Background Art

[0002] Polymyxin B sulfate is an important drug. In its quality control and research, accurate analysis and detection are crucial. As a key component in analysis and detection, the change in the column efficiency of the chromatographic column will have a significant impact on the detection results of polymyxin B sulfate.

[0003] In the above-mentioned prior art, in the analysis and detection of polymyxin B sulfate, there is a lack of effective methods for monitoring the column efficiency of the chromatographic column and evaluating its impact on the detection resolution. At the same time, it is difficult to accurately predict the service life of the chromatographic column, which may lead to inaccurate detection results, low experimental efficiency, and waste of resources;

[0004] Therefore, this application records the historical column efficiency values when the chromatographic column analyzes and detects polymyxin B sulfate multiple times, and conducts trend change analysis to determine whether the column efficiency has decreased. If the overall column efficiency shows a downward trend within the historical detection period, the change trend type of multiple column efficiency values is identified, indirectly reflecting the change in the overall trend of the historical column efficiency change curve. Moreover, according to the identified change trend type, a column life prediction model is constructed, so as to provide data support for inferring the corresponding column efficiency of the chromatographic column in the later stage. And by dividing the constructed historical separation change curve to obtain historical sub-separation lines, iterative fitting analysis is carried out, the fitting line with high fitting matching degree is selected, and the corresponding slope is obtained as the slope of the historical sub-separation line, which helps to improve the characterization accuracy of the slope of the historical sub-separation line, and at the same time reflects that it has a relatively high important weight ratio in the aspect of the detection accuracy of the content of polymyxin B sulfate. Therefore, the importance of the column efficiency of the chromatographic column itself is emphasized;

[0005] According to the identified change trend type, the predicted column life loss degree and the current column efficiency value of the current chromatographic column for analyzing and detecting polymyxin B sulfate are obtained, and the predicted remaining column life value is obtained, solving the problem that the service life of the chromatographic column cannot be accurately known in the analysis and detection of polymyxin B sulfate. By predicting the service life of the chromatographic column, it helps the experimenters to understand the usage status of the chromatographic column in advance, replace the chromatographic column in time, ensure the accuracy and reliability of the analysis and detection results of polymyxin B sulfate, avoid affecting the detection accuracy due to the aging of the chromatographic column, and at the same time can reasonably arrange the experimental process and improve the experimental efficiency.

[0006] Therefore, the present invention provides an analysis and detection method for polymyxin B sulfate. Summary of the Invention

[0007] To make up for the deficiencies of the prior art and solve at least one technical problem proposed in the background art.

[0008] The technical solution adopted by the present invention to solve its technical problems is as follows:

[0009] An analytical detection method for polymyxin B sulfate, comprising the following steps:

[0010] During the historical detection period, record the historical column efficiency values of multiple chromatographic column analyses and detections of polymyxin B sulfate, and conduct a trend change analysis to determine whether the column efficiency has decreased.

[0011] If the column efficiency of the chromatographic column decreases, analyze the type of change trend of the column efficiency value corresponding to the analysis and detection operation of polymyxin B sulfate to determine the type of column efficiency change trend.

[0012] Among them, the type of change trend includes a stable decline type or a fluctuating decline type.

[0013] During the historical detection period, obtain the historical resolution after each analysis and detection operation, analyze the correlation with the historical column efficiency value, and evaluate the influence degree of the column efficiency corresponding to the chromatographic column on the detection resolution.

[0014] If the influence degree is large, according to the identified type of change trend, obtain the predicted column life loss degree, and the column efficiency value of the current chromatographic column for analyzing and detecting polymyxin B sulfate, and conduct a combined analysis to obtain the predicted remaining column life value.

[0015] As a preferred solution of the present invention: The method for obtaining the historical column efficiency value is as follows:

[0016] Respectively obtain the half-peak width and retention time on the liquid chromatograph corresponding to the chromatographic column analysis and detection operation, and input them into the theoretical plate number calculation formula to output the historical column efficiency value.

[0017] As a preferred solution of the present invention: The trend change analysis of the historical column efficiency values of multiple chromatographic column analysis and detection operations is as follows:

[0018] Evenly divide the historical detection period into several historical detection time periods;

[0019] Extract the historical column efficiency values within each detection time period, and construct a historical column efficiency change curve according to the time series of the corresponding time periods, and divide it into several historical column efficiency sub-curves.

[0020] On the historical column efficiency sub - curve, extract any two corresponding coordinates, perform simulation fitting by the least - squares method to obtain the simulated column efficiency fitting line, and obtain the area of the closed figure formed by the corresponding historical column efficiency sub - curve, then perform summation calculation to obtain the fitting column efficiency matching degree. If it is less than or equal to the standard fitting matching degree, use the simulated fitting line as the column efficiency reference line, and calculate the slope of the historical column efficiency sub - curve through the slope calculation formula.

[0021] As a preferred solution of the present invention: The process of judging whether the column efficiency decreases is as follows:

[0022] Count the number of historical column efficiency sub - fitting lines with a negative slope of the historical column efficiency sub - curve and the number of historical column efficiency sub - fitting lines with a positive slope of the historical column efficiency sub - curve;

[0023] If the number of historical column efficiency sub - fitting lines with a negative slope of the sub - fitting line is greater than the number of historical column efficiency sub - fitting lines with a positive slope of the sub - fitting line, generate a column efficiency decrease signal.

[0024] As a preferred solution of the present invention: The process of identifying the change trend type is as follows:

[0025] Combine the slopes of adjacent historical column efficiency sub - curves to obtain multiple sub - curve slope groups, and process the slopes of the historical column efficiency sub - curves within the multiple sub - curve slope groups through the Mahalanobis distance formula to obtain the trend type identification value;

[0026] If the trend type identification value is greater than the trend type identification threshold, it is a fluctuating decline type;

[0027] If the trend type identification value is less than or equal to the trend type identification threshold, it is a stable decline type.

[0028] As a preferred solution of the present invention: The process of obtaining the historical resolution is as follows:

[0029] During any historical detection period, obtain the content of polymyxin B sulfate after extraction and calculate the ratio with the content of the extract before extraction to obtain the historical resolution.

[0030] As a preferred solution of the present invention: The process of analyzing the correlation between the detection resolution and the historical column efficiency value is as follows:

[0031] Respectively extract the historical resolution and the historical column efficiency value in all historical detection periods;

[0032] Based on the historical resolution in all historical detection periods, construct a historical resolution change curve and divide it into several historical resolution sub - curves;

[0033] On the historical separation sub-curve, extract any two corresponding coordinates, perform simulation fitting by the least squares method to obtain the simulated separation fitting line, sum up the areas of all closed figures formed by the historical separation sub-curve, obtain the fitting separation matching degree. If it is less than or equal to the standard fitting matching degree, use the simulated fitting line as the separation reference line, and calculate the slope of the historical separation sub-curve through the slope calculation formula;

[0034] Based on the same historical detection period as the benchmark, extract the slopes of the corresponding historical separation sub-curve and the historical column efficiency sub-curve respectively, and process the slopes of the historical separation sub-curve and the historical column efficiency sub-curve corresponding to all historical detection periods according to the historical detection period through the Mahalanobis distance formula, and output to obtain the column efficiency separation correlation degree.

[0035] As a preferred solution of the present invention: the process of evaluating the influence degree of the column efficiency value corresponding to the chromatographic column on the detection separation degree is as follows:

[0036] If the column efficiency separation correlation degree is greater than the preset standard correlation degree, generate a small signal of low column efficiency influence;

[0037] If the column efficiency separation correlation degree is less than or equal to the preset standard correlation degree, generate a large signal of high column efficiency influence.

[0038] As a preferred solution of the present invention: the process of obtaining the column life loss degree is as follows:

[0039] If it is a type of fluctuating decline, perform difference processing on the Y-axis coordinates of adjacent coordinate points on the historical column efficiency change curve, output to obtain the adjacent decline difference, extract the maximum adjacent decline difference and the minimum adjacent decline difference for averaging calculation, and output to obtain the predicted column life loss degree;

[0040] If it is a type of stable decline, perform difference processing on the Y-axis coordinates of adjacent coordinate points on the historical column efficiency change curve, and output to obtain the adjacent decline difference;

[0041] Perform averaging calculation on all adjacent decline differences, and output to obtain the predicted column life loss degree.

[0042] As a preferred solution of the present invention: the process of obtaining the predicted remaining column life value is as follows:

[0043] Calculate the ratio of the current column efficiency value to the predicted column life loss degree to obtain the predicted remaining column life value.

[0044] The beneficial effects of the present invention are as follows:

[0045] 1. During the historical detection period of the present invention, the historical column efficiency values are recorded when the chromatographic column analyzes and detects polymyxin B sulfate multiple times, and trend change analysis is performed to determine whether the column efficiency decreases. If the overall column efficiency shows a downward trend during the historical detection period, the change trend types of multiple column efficiency values are identified, which not only indirectly reflects the change of the overall trend of the historical column efficiency change curve, but also can intuitively reflect the difference degree between different sub-curve slope groups. Furthermore, it helps to classify and identify the trend types of the historical column efficiency change curve, provides an important basis for constructing a column life prediction model, and constructs a column life prediction model according to the identified change trend types, so as to provide data support for inferring the corresponding column efficiency of the chromatographic column later;

[0046] 2. During the historical detection period of the present invention, the historical resolution after each analysis and detection is obtained. The historical separation sub-curves are obtained by dividing the constructed historical separation change curve, and iterative fitting analysis is performed. The fitting line with a high fitting matching degree is selected, and the corresponding slope is obtained as the slope of the historical separation sub-curve, which helps to improve the characterization accuracy of the slope of the historical separation sub-curve. Based on the same historical detection period, the slopes of the corresponding historical separation sub-curves and the slopes of the historical column efficiency sub-curves are respectively extracted and compared for correlation. If the correlation is large, it indicates that the column efficiency of the chromatographic column itself is of high importance when analyzing and detecting polymyxin B sulfate, especially in terms of the accuracy of the content detection of polymyxin B sulfate, with a high important weight ratio. Therefore, the importance of the column efficiency of the chromatographic column itself is emphasized;

[0047] 3. According to the identified change trend type, the present invention obtains the predicted column life loss degree and the current column efficiency value of the current chromatographic column for analyzing and detecting polymyxin B sulfate, calculates the ratio of the current column efficiency value to the predicted column life loss degree to obtain the predicted remaining column life value, which solves the problem that in the analysis and detection of polymyxin B sulfate, the service life of the chromatographic column cannot be accurately known. By predicting the service life of the chromatographic column, it helps the experimenters to understand the usage status of the chromatographic column in advance, replace the chromatographic column in time, ensure the accuracy and reliability of the analysis and detection results of polymyxin B sulfate, avoid affecting the detection accuracy due to chromatographic column aging, and at the same time can reasonably arrange the experimental process and improve the experimental efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The present invention will be further described below with reference to the accompanying drawings.

[0049] Figure 1 is the flow chart of the idea of an analysis and detection method for polymyxin B sulfate of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0050] In order to make the technical means, creative features, achieved objectives and effects of the present invention easy to understand, the present invention will be further described below in conjunction with specific embodiments.

[0051] Example 1

[0052] Please refer to Figure 1 As shown, an analysis and detection method for polymyxin B sulfate according to an embodiment of the present invention includes the following steps:

[0053] Step 1: During the historical detection period, record the historical column efficiency values when the chromatographic column analyzes and detects polymyxin B sulfate multiple times, and perform trend change analysis to determine whether the column efficiency has decreased;

[0054] In a preferred embodiment, the process of obtaining the historical column efficiency value is as follows:

[0055] Extract the liquid chromatography when the chromatographic column analyzes and detects polymyxin B sulfate each time;

[0056] Use Shimadzu LC Solution software to obtain the half-peak width and retention time on the liquid chromatography respectively, and input them into the theoretical plate number calculation formula: , to obtain the historical column efficiency value , where represents the retention time, represents the half-peak width;

[0057] Evenly divide the historical detection period into several historical detection time periods;

[0058] Extract the historical column efficiency values within each detection time period, and construct a historical column efficiency change curve according to the time series of the corresponding time periods, where the X-axis is time and the Y-axis is the historical column efficiency value;

[0059] Divide the historical column efficiency change curve into several historical column efficiency sub-curves;

[0060] It should be noted that the historical column efficiency sub-curve is divided by taking the local historical column efficiency change curve between adjacent coordinates on the historical column efficiency change curve as the historical column efficiency sub-curve;

[0061] It should be noted that the number of historical column efficiency sub-curves is odd;

[0062] On the historical column efficiency sub-curve, randomly extract two corresponding coordinates, and perform simulation fitting by the least squares method to obtain a simulated column efficiency fitting line;

[0063] Extract the closed figure formed by the simulated column efficiency fitting line and the corresponding historical column efficiency sub-curve, and obtain the sum of the areas of the closed figures for calculation to obtain the fitting column efficiency matching degree;

[0064] It can be understood that the meaning represented by the fitting column efficiency matching degree is: the sum of the areas of all closed figures formed between the historical column efficiency sub-curves and the simulated column efficiency fitting line, which is a quantitative index used to evaluate the fitting degree of the simulated column efficiency fitting line to the historical column efficiency sub-curves. Specifically, the smaller the fitting column efficiency matching degree, the smaller the difference between the historical column efficiency sub-curves and the simulated column efficiency fitting line; the larger the fitting column efficiency matching degree, the larger the difference between the historical column efficiency sub-curves and the simulated column efficiency fitting line;

[0065] If the fitting column efficiency matching degree is greater than the standard fitting matching degree, it indicates that the difference between the historical column efficiency sub-curves and the simulated column efficiency fitting line is large and the matching degree is low. Iterative simulation fitting operations need to be performed on the simulated column efficiency fitting line until the fitting column efficiency matching degree is less than or equal to the standard fitting matching degree;

[0066] If the fitting column efficiency matching degree is less than or equal to the standard fitting matching degree, it means that the difference between the historical column efficiency sub-curves and the simulated column efficiency fitting line is small and the matching degree is high. The simulated fitting line is used as the column efficiency reference line, and the slope of the historical column efficiency sub-curves is calculated through the slope calculation formula;

[0067] It should be noted that the slopes of multiple historical column efficiency sub-curves are not zero;

[0068] Count the number of historical column efficiency sub-fitting lines with a negative slope of the historical column efficiency sub-curves and the number of historical column efficiency sub-fitting lines with a positive slope of the historical column efficiency sub-curves;

[0069] If the number of historical column efficiency sub-fitting lines with a negative slope of the sub-fitting line is greater than the number of historical column efficiency sub-fitting lines with a positive slope of the sub-fitting line, it indicates that the overall historical column efficiency change curve shows a downward trend, and a column efficiency decline signal is generated;

[0070] If the number of historical column efficiency sub-fitting lines with a negative slope of the sub-fitting line is less than the number of historical column efficiency sub-fitting lines with a positive slope of the sub-fitting line, it indicates that the overall historical column efficiency change curve does not show a downward trend, and a non-column efficiency decline signal is generated;

[0071] Step 2: If the column efficiency of the chromatographic column decreases, analyze the change trend type of the column efficiency values corresponding to multiple chromatographic column analysis and detection operations to judge the column efficiency change trend type;

[0072] Among them, the change trend types include but are not limited to a stable decline type or a fluctuating decline type;

[0073] Exemplarily, after sorting all the slopes of the historical column efficiency sub-curves according to the corresponding historical column efficiency sub-curves on the historical column efficiency change curve, the adjacent slopes of the historical column efficiency sub-curves are combined to obtain multiple sub-curve slope groups;

[0074] Process the historical column efficiency sub - curve slopes within multiple sub - curve slope groups using the Lance distance formula to obtain trend type recognition values ;

[0075] Specifically, the Lance distance formula: , where represents one of the historical column efficiency sub - curve slopes within the th sub - curve slope group, represents another historical column efficiency sub - curve slope within the th sub - curve slope group, represents the total number of sub - curve slope groups;

[0076] It should be noted that the purpose of using the Lance distance formula is as follows: The Lance distance formula can quantify the differences between the historical column efficiency sub - curve slopes within the sub - curve slope group. Through the calculated trend type recognition values, the degree of difference between different sub - curve slope groups can be intuitively reflected. By comparing different historical column efficiency sub - curve slopes, it helps to identify the trend type of the historical column efficiency change curve, thereby providing data support for inferring the corresponding column efficiency of the chromatographic column in the later stage;

[0077] It can be understood that the meaning represented by the trend type recognition value is: Since the historical column efficiency sub - curve slope reflects the change trend of the historical column efficiency change curve in different local parts, the trend type recognition value not only indirectly reflects the change of the overall trend of the historical column efficiency change curve, but also can intuitively reflect the degree of difference between different sub - curve slope groups, thus helping to classify and identify the trend type of the historical column efficiency change curve and providing an important basis for constructing a column life prediction model;

[0078] Compare the trend type recognition value with the trend type recognition threshold, and the process is as follows:

[0079] If the trend type recognition value is greater than the trend type recognition threshold, it indicates that the slope change of the historical column efficiency change curve at different stages is relatively large, and the overall downward trend has fluctuations, then it is the fluctuating downward type;

[0080] If the trend type recognition value is less than or equal to the trend type recognition threshold, it indicates that the slope change of the historical column efficiency change curve at different stages is relatively small, and the overall downward trend is relatively stable, then it is the stable downward type;

[0081] Specifically, in this embodiment: during the historical detection period, record the historical column efficiency values when the chromatographic column analyzes and detects polymyxin B sulfate multiple times, and perform trend change analysis to determine whether the column efficiency decreases. If the overall column efficiency shows a downward trend during the historical detection period, identify the change trend types of multiple column efficiency values, which can not only indirectly reflect the change of the overall trend of the historical column efficiency change curve, but also intuitively reflect the difference degree between different sub-curve slope groups, thereby helping to classify and identify the trend types of the historical column efficiency change curve, providing an important basis for constructing a column life prediction model, and constructing a column life prediction model according to the identified change trend types, so as to provide data support for inferring the corresponding column efficiency of the chromatographic column later.

[0082] Example 2

[0083] As Figure 1 shown, an analysis and detection method for polymyxin B sulfate according to an embodiment of the present invention includes the following steps:

[0084] Step three: during the historical detection period, obtain the historical resolution after each analysis and detection, analyze the correlation between the detection resolution and the historical column efficiency value, and evaluate the influence degree of the column efficiency value corresponding to the chromatographic column on the detection resolution;

[0085] In a preferred embodiment, the process of obtaining the historical resolution is as follows:

[0086] During any historical detection period, obtain the content of polymyxin B sulfate after extraction, and calculate the ratio with the content of the extraction solution before extraction to obtain the historical resolution;

[0087] It should be noted that the content of the extraction solution before extraction includes, but is not limited to, the content of the common extraction solution known to those skilled in the art when extracting polymyxin B sulfate;

[0088] Extract the historical resolution and the historical column efficiency value in all historical detection periods respectively;

[0089] Based on the historical resolution in all historical detection periods, construct a historical separation change curve;

[0090] Divide the historical separation change curve into several historical sub-separation curves;

[0091] It should be noted that the way of dividing the historical sub-separation curves is the same as that of the historical column efficiency sub-curves, and the total number of the historical sub-separation curves and the historical column efficiency sub-curves is the same and is odd;

[0092] On the historical sub-separation curve, randomly extract two corresponding coordinates, and perform simulation fitting by the least square method to obtain a simulation separation fitting line;

[0093] Extract the closed figure formed by the simulated separation fitting line and the corresponding historical separation sub-curve, and obtain the sum of the areas of the closed figures for calculation to obtain the fitting separation matching degree;

[0094] It can be understood that the meaning represented by the fitting separation matching degree is: the sum of the areas of all the closed figures formed between the historical separation sub-curve and the simulated separation fitting line, which is a quantitative index used to evaluate the fitting degree of the simulated separation fitting line to the historical separation sub-curve. Specifically, the smaller the fitting separation matching degree, the smaller the difference between the simulated separation fitting line and the historical separation sub-curve; the higher the fitting separation matching degree, the greater the difference between the simulated separation fitting line and the historical separation sub-curve, and the lower the fitting separation matching degree;

[0095] If the fitting separation matching degree is greater than the standard fitting matching degree, it means that the difference between the simulated separation fitting line and the historical separation sub-curve is small and the fitting separation matching degree is high. An iterative simulation fitting operation needs to be performed on the simulated separation fitting line until the fitting separation matching degree is less than or equal to the standard fitting matching degree;

[0096] If the fitting separation matching degree is less than or equal to the standard fitting matching degree, it means that the difference between the simulated separation fitting line and the historical separation sub-curve is large and the fitting separation matching degree is low. The simulated fitting line is used as the separation reference line, and the slope of the historical separation sub-curve is calculated through the slope calculation formula;

[0097] It should be noted that the slopes of multiple historical separation sub-curves are not zero;

[0098] Based on the same historical detection period, extract the slopes of the corresponding historical separation sub-curves and the slopes of the historical column efficiency sub-curves respectively;

[0099] Input the slopes of the historical separation sub-curves and the slopes of the historical column efficiency sub-curves corresponding to all historical detection periods into the Lance distance formula according to the time series of the historical detection periods, and output the column efficiency separation correlation degree ;

[0100] Specifically, the Lance distance formula: , where represents the slope of the historical separation sub-curve in the th historical detection period, represents the slope of the historical column efficiency sub-curve in the th historical detection period, represents the total number of historical detection periods;

[0101] It should be noted that the purpose of using the Lance distance formula is as follows: the column efficiency separation correlation degree output by the Lance distance formula is a specific value, which provides a quantitative index for analyzing the relationship between the historical column efficiency value and the historical separation degree. It is possible to intuitively judge the tightness of the association between the two based on the size of this index, which is convenient for comparison and evaluation;

[0102] It can be understood that the meaning represented by the column efficiency separation correlation degree is as follows: comprehensively considering the changes in the slopes of the historical separation sub-curves and the historical column efficiency sub-curves during all historical detection periods. Specifically, the slope of the historical separation sub-curve reflects the changing trend of the historical separation degree over time, and the slope of the historical column efficiency sub-curve reflects the changing trend of the historical column efficiency value over time. Using the column efficiency separation correlation degree to quantitatively reflect the similarity between the slopes of these two groups reflecting the changing trends means that the column efficiency of the chromatographic column itself is of relatively high importance when analyzing and detecting polymyxin B sulfate, especially in terms of the accuracy of the content detection of polymyxin B sulfate, with a relatively high important weight ratio;

[0103] If the column efficiency separation correlation degree is greater than the preset standard correlation degree, it indicates that the changing trends of the historical column efficiency value and the historical separation degree are quite different, and the correlation degree is not tight, generating a small signal of column efficiency influence;

[0104] If the column efficiency separation correlation degree is less than or equal to the preset standard correlation degree, it indicates that the changing trends of the historical column efficiency value and the historical separation degree are less different, and the correlation degree is relatively tight, generating a large signal of column efficiency influence;

[0105] This embodiment is specifically as follows: within the historical detection period, obtain the historical separation degree after each analysis and detection. By dividing the constructed historical separation change curve, obtain the historical separation sub-lines, conduct iterative fitting analysis, select the fitting lines with high fitting matching degree, and obtain the corresponding slopes as the slopes of the historical separation sub-lines, which helps to improve the characterization accuracy of the slopes of the historical separation sub-lines. Based on the same historical detection period, extract the corresponding slopes of the historical separation sub-curves and the historical column efficiency sub-curves respectively, and conduct a correlation degree comparison. If the correlation degree is large, it indicates that the column efficiency of the chromatographic column itself is of relatively high importance when analyzing and detecting polymyxin B sulfate, especially in terms of the accuracy of the content detection of polymyxin B sulfate. Therefore, the importance of the column efficiency of the chromatographic column itself is emphasized.

[0106] Example 3

[0107] As Figure 1 shown, an analysis and detection method for polymyxin B sulfate according to an embodiment of the present invention further includes the following steps:

[0108] Step 4: According to the identified type of change trend, obtain the predicted column life loss degree and the current column efficiency value of the current chromatographic column for the analysis and detection of polymyxin B sulfate, and perform a combined analysis to obtain the predicted remaining column life value;

[0109] In a preferred embodiment, if it is a type of fluctuating decline, perform a difference processing on the Y-axis coordinates of adjacent coordinate points on the historical column efficiency change curve, output the adjacent decline difference, extract the maximum adjacent decline difference and the minimum adjacent decline difference for averaging calculation, and output the predicted column life loss degree;

[0110] If it is a type of stable decline, perform a difference processing on the Y-axis coordinates of adjacent coordinate points on the historical column efficiency change curve, and output the adjacent decline difference;

[0111] Perform an averaging calculation on all adjacent decline differences, and output the predicted column life loss degree;

[0112] Perform a ratio calculation on the current column efficiency value and the predicted column life loss degree to obtain the predicted remaining column life value;

[0113] Specifically, in this embodiment: According to the identified type of change trend, obtain the predicted column life loss degree and the current column efficiency value of the current chromatographic column for the analysis and detection of polymyxin B sulfate, perform a ratio calculation on the current column efficiency value and the predicted column life loss degree to obtain the predicted remaining column life value, which solves the problem that in the analysis and detection of polymyxin B sulfate, it is impossible to accurately know the service life of the chromatographic column. By predicting the service life of the chromatographic column, it helps the experimenters to understand the usage status of the chromatographic column in advance, replace the chromatographic column in time, ensure the accuracy and reliability of the analysis and detection results of polymyxin B sulfate, avoid affecting the detection accuracy due to the aging of the chromatographic column, and at the same time can reasonably arrange the experimental process and improve the experimental efficiency.

[0114] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed. The scope of protection claimed by the present invention is defined by the appended claims and their equivalents.

Claims

1. An analytical detection method for polymyxin B sulfate, characterized in that: Including: During the historical detection period, record the historical column efficiency values of multiple chromatographic column analyses and detections of polymyxin B sulfate, and conduct trend change analysis to determine whether the column efficiency has decreased; If the column efficiency of the chromatographic column decreases, analyze the change trend type of the column efficiency value corresponding to the polymyxin B sulfate analysis and detection operation to determine the change trend type of the column efficiency; Among them, the change trend types include stable decline type or fluctuating decline type; During the historical detection period, obtain the historical resolution after each analysis and detection operation, analyze the correlation with the historical column efficiency value, and evaluate the influence degree of the column efficiency corresponding to the chromatographic column on the detection resolution; If the influence degree is large, according to the identified change trend type, obtain the predicted column life loss degree, and the column efficiency value of the current chromatographic column for the analysis and detection of polymyxin B sulfate, and conduct combined analysis to obtain the predicted remaining column life value; The process of analyzing the correlation between the analysis and detection resolution and the historical column efficiency value is as follows: Extract the historical resolution and historical column efficiency values during all historical detection periods respectively; Based on the historical resolution during all historical detection periods, construct a historical separation change curve and divide it into several historical sub-separation curves; On the historical sub-separation curve, randomly extract two corresponding coordinates, and perform simulation fitting through the least squares method to obtain a simulated separation fitting line, and sum the areas of all closed figures formed by the historical sub-separation curves to obtain a fitting separation matching degree. If it is less than or equal to the standard fitting matching degree, use the simulated fitting line as the separation reference line, and calculate the slope of the historical sub-separation curve through the slope calculation formula; Based on the same historical detection period as the benchmark, extract the slopes of the corresponding historical sub-separation curves and historical column efficiency sub-curves respectively, and process the slopes of the historical sub-separation curves and historical column efficiency sub-curves corresponding to all historical detection periods according to the historical detection period through the Mahalanobis distance formula, and output the column efficiency-separation correlation degree; The process of obtaining the predicted column life loss degree is as follows: If it is a fluctuating decline type, perform difference processing on the Y-axis coordinates of adjacent coordinate points on the historical column efficiency change curve, output the adjacent decline difference, extract the maximum adjacent decline difference and the minimum adjacent decline difference for averaging calculation, and output the predicted column life loss degree; If it is a stable decline type, perform difference processing on the Y-axis coordinates of adjacent coordinate points on the historical column efficiency change curve, and output the adjacent decline difference; Perform averaging calculation on all adjacent decline differences, and output the predicted column life loss degree.

2. The analytical detection method of polymyxin B sulfate according to claim 1, wherein: The method for obtaining the historical column efficiency value is: Respectively obtain the half-peak width and retention time on the liquid chromatograph corresponding to the chromatographic column analysis and detection operation, and input them into the theoretical plate number calculation formula, and output the historical column efficiency value.

3. The analytical detection method of polymyxin B sulfate according to claim 1, wherein: The process of trend change analysis of the historical column efficiency values of multiple chromatographic column analysis and detection operations is as follows: Evenly divide the historical detection period into several historical detection periods; Extract the historical column efficiency values within each detection period, and construct a historical column efficiency change curve according to the time series of the corresponding period, and divide it into several historical column efficiency sub-curves; On the historical column efficiency sub-curve, extract any two corresponding coordinates and perform simulation fitting by the least squares method to obtain the simulated column efficiency fitting line. Then, obtain the area of the closed figure formed by the corresponding historical column efficiency sub-curve and perform summation calculation to get the fitting column efficiency matching degree. If it is less than or equal to the standard fitting matching degree, use the simulated fitting line as the column efficiency reference line and calculate the slope of the historical column efficiency sub-curve through the slope calculation formula.

4. The analytical detection method of polymyxin B sulfate according to claim 3, wherein: The process of judging whether the column efficiency has decreased is as follows: Count the number of historical column efficiency sub-fitting lines with a negative slope of the historical column efficiency sub-curve and the number of historical column efficiency sub-fitting lines with a positive slope of the historical column efficiency sub-curve; If the number of historical column efficiency sub-fitting lines with a negative slope of the sub-fitting line is greater than the number of historical column efficiency sub-fitting lines with a positive slope of the sub-fitting line, generate a column efficiency decrease signal.

5. The analytical detection method of polymyxin B sulfate according to claim 3, characterized in that: The process of identifying the change trend type is as follows: Combine the slopes of adjacent historical column efficiency sub-curves to obtain multiple sub-curve slope groups, and process the slopes of the historical column efficiency sub-curves within the multiple sub-curve slope groups through the Mahalanobis distance formula to obtain the trend type identification value; If the trend type identification value is greater than the trend type identification threshold, it is the fluctuating decrease type; If the trend type identification value is less than or equal to the trend type identification threshold, it is the stable decrease type.

6. The analytical detection method of polymyxin B sulfate according to claim 1, characterized in that: The process of obtaining the historical resolution is as follows: During any historical detection period, obtain the content of polymyxin B sulfate after extraction and calculate the ratio with the content of the extract before extraction to obtain the historical resolution.

7. The analytical detection method of polymyxin B sulfate according to claim 5, characterized in that: The process of evaluating the influence degree of the column efficiency value corresponding to the chromatographic column on the detection resolution is as follows: If the column efficiency-separation correlation degree is greater than the preset standard correlation degree, generate a small signal of low column efficiency influence; If the column efficiency-separation correlation degree is less than or equal to the preset standard correlation degree, generate a large signal of high column efficiency influence.

8. The analytical detection method of polymyxin B sulfate according to claim 1, wherein: The process of obtaining the predicted remaining column life value is as follows: Calculate the ratio of the current column efficiency value to the predicted column life loss degree to obtain the predicted remaining column life value.

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