CN115798573B - Method and device for analyzing pharmaceutical ingredients - Google Patents
Method and device for analyzing pharmaceutical ingredients Download PDFInfo
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Abstract
The invention relates to a method and a device for analyzing medicine components, comprising the following steps: generating a sample solution of a target drug, and performing attribute configuration on a preset chromatograph according to the sample solution to obtain a configured chromatograph; performing multiple verification on the prepared chromatograph according to the sample solution, and determining that the chromatograph passing the verification is a standard chromatograph; generating test data of the test sample solution by using the standard chromatograph, and generating a fingerprint of the test sample solution according to the test data; screening out characteristic peaks of the sample solution according to the fingerprint, and determining the components of the target medicament by using a preset reference fingerprint and the characteristic peaks. The invention can improve the efficiency of the analysis of the components of the medicine.
Description
Technical Field
The invention relates to the technical field of artificial intelligence, in particular to a method and a device for analyzing medicine components.
Background
How to effectively identify and evaluate the national medicines is an important problem for restricting the development of the national medicines, the quality of the medicines is influenced by a plurality of factors, such as the type, the production place, the harvesting period, the processing method and the like, and the simple analysis of one or more chemical components is used for judging whether the treatment effect, the stability and the controllable thought of the medicines are not suitable for the national medicines with complex chemical components.
Disclosure of Invention
The invention provides a method and a device for analyzing medicine components, and mainly aims to solve the problem of low efficiency in medicine component analysis.
In order to achieve the above object, the present invention provides a method for analyzing pharmaceutical ingredients, comprising:
obtaining target medicines in different batches, and preprocessing the target medicines to obtain test samples of the target medicines;
preparing a plurality of sample solutions of the test samples according to the test samples, and performing attribute configuration on a preset chromatograph according to the sample solutions to obtain a configured chromatograph;
selecting one of the sample solutions as a target solution, performing multiple verification on the prepared chromatograph according to the target solution, and determining that the chromatograph passing the verification is a standard chromatograph;
performing chromatographic analysis on the sample solution by using the standard chromatograph to obtain test data of the sample solution, and generating a fingerprint of the sample solution according to the test data;
screening out characteristic peaks of the sample solution according to the fingerprint, and determining the components of the target medicament by using a preset reference fingerprint and the characteristic peaks.
Optionally, the multiple verification of the configured chromatograph according to the target solution includes:
generating a target chromatogram of the target solution according to the target solution and the configured chromatograph;
performing precision verification on the configured chromatograph according to the chromatogram, and determining that the chromatograph which is configured to be completed through the precision verification is a primary verification chromatograph;
performing stability verification on the primary verification chromatograph according to the chromatogram, and determining that the primary verification chromatograph passing the stability verification is a secondary verification chromatograph;
and carrying out repeatability verification on the secondary verification chromatograph according to the chromatogram, and determining that the secondary verification chromatograph passing the repeatability verification is a standard chromatograph.
Optionally, the performing precision verification on the configured chromatograph according to the chromatogram, determining that the configured chromatograph is a primary verification chromatograph through precision verification, including:
obtaining the peak area of a common peak in the chromatogram, and generating the area ratio of the common peak according to the peak area;
the relative standard deviation of the common peak is calculated using the following relative standard deviation algorithm and the area ratio:
wherein ,
is the relative standard deviation of the common peak, < >>
Is the total of the area ratios, +.>
Is->
The area ratio of the individual said common peaks, < >>
Is the identity of the common peak, +.>
Is the average of the area ratios.
And when the relative standard deviation is smaller than a preset deviation threshold, verifying the configured chromatograph through precision.
Optionally, the performing stability verification on the primary verification chromatograph according to the chromatogram, determining that the primary verification chromatograph passing the stability verification is a secondary verification chromatograph, including:
sequencing and combining the chromatograms according to time sequence to obtain a synthetic chromatogram of the chromatogram;
selecting one of the characteristic peaks in the synthetic chromatogram as a target characteristic peak, and calculating the relative retention time of the target characteristic peak at different times;
and calculating the feature similarity of the target feature peak according to the relative retention time, and when the feature similarity is larger than a preset similarity threshold value, verifying the stability by the primary verification chromatograph.
Optionally, the screening the characteristic peaks of the sample solution according to the fingerprint spectrum includes:
removing noise from the fingerprint to obtain a first-level fingerprint of the fingerprint;
analyzing the overlapped peaks in the primary spectrum to obtain a secondary spectrum of the primary spectrum;
and carrying out standardization treatment on the signal intensity in the secondary spectrum to obtain a standard spectrum of the secondary spectrum, and determining a characteristic peak of the sample solution according to the standard spectrum.
Optionally, the removing noise from the fingerprint spectrum to obtain a first-level spectrum of the fingerprint spectrum includes:
and removing noise from the fingerprint spectrum by using the following linear filtering algorithm to obtain a primary spectrum of the fingerprint spectrum:
wherein ,
is a dimension +.>
Is>
Is a transposed matrix of the filter coefficient matrix, < >>
Pixel gray matrix of the fingerprint spectrum covered by the filter, < >>
Is a convolution matrix of the fingerprint;
and determining a first-level map of the fingerprint map according to the convolution matrix.
Optionally, the analyzing the overlapping peaks in the primary spectrum to obtain a secondary spectrum of the primary spectrum includes:
determining one of the overlapping peaks in the primary spectrum as a target peak, determining a trough of the target peak according to the target peak, and determining Zuo Feng and a right peak of the target peak according to the trough;
calculating the left area of the left peak according to the left peak height and the bottom left half peak width of the left peak, and calculating the right area of the right peak according to the right peak height and the bottom right half peak width of the right peak;
and eliminating peak errors of the overlapped peaks according to the left area and the right area to obtain a secondary spectrum of the primary spectrum.
Optionally, the normalizing the signal intensity in the secondary spectrum to obtain a standard spectrum of the secondary spectrum includes:
selecting one chromatographic peak in the secondary spectrum one by one as a standard peak, and calculating the standard area of the standard peak according to the signal intensity in the secondary spectrum;
adding the standard areas to obtain the total peak area of the secondary map;
and calculating the normalized area of the standard peak according to the total peak area and the standard area, and carrying out normalization processing on the secondary spectrum according to the normalized area to obtain a standard spectrum of the secondary spectrum.
In order to solve the above problems, the present invention also provides a device for analyzing a pharmaceutical composition based on a fingerprint, the device comprising:
the test sample module is used for obtaining target medicines in different batches, and preprocessing the target medicines to obtain test samples of the target medicines;
the attribute configuration module is used for preparing a plurality of sample solutions of the test samples according to the test samples, and performing attribute configuration on a preset chromatograph according to the sample solutions to obtain the configured chromatograph;
the multiple verification module is used for selecting one of the sample solutions to be used as a target solution, carrying out multiple verification on the prepared chromatograph according to the target solution, and determining that the chromatograph passing the verification is a standard chromatograph;
the fingerprint spectrum module is used for carrying out chromatographic analysis on the sample solution by utilizing the standard chromatograph to obtain test data of the sample solution, and generating a fingerprint spectrum of the sample solution according to the test data;
and the medicine component module is used for screening out characteristic peaks of the sample solution according to the fingerprint, and determining the components of the target medicine by utilizing a preset reference fingerprint and the characteristic peaks.
According to the invention, target medicines in different batches are obtained, pretreatment is carried out on the target medicines to obtain a test sample of the target medicines, so that the target medicines have enough representativeness, the obtained fingerprint has more biological significance, the preset chromatograph is configured according to the sample solution to obtain the configured chromatograph, the error testing time of the subsequent sample solution is saved, the separation efficiency of the sample solution is improved, the configured chromatograph is subjected to multiple verification, the rationality and superiority of chromatographic conditions are ensured, the reliability of test results is ensured, the components of the sample solution are determined to be obtained by calculating the similarity of the generated characteristic peaks based on a large amount of data according to the standard chromatograph and the preset reference fingerprint, the identification accuracy is improved, and the identification time is saved.
Drawings
FIG. 1 is a flow chart of a method for analyzing pharmaceutical ingredients according to an embodiment of the present invention;
FIG. 2 is a flow chart illustrating a stability verification according to an embodiment of the present invention;
FIG. 3 is a flow chart illustrating the analysis of overlapping peaks according to an embodiment of the present invention;
FIG. 4 is a functional block diagram of a pharmaceutical composition analysis device according to an embodiment of the present invention;
the achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The embodiment of the application provides a medicine component analysis method based on fingerprint. The execution subject of the fingerprint-based pharmaceutical composition analysis method includes, but is not limited to, at least one of a server, a terminal, and the like, which can be configured to execute the method provided in the embodiments of the present application. In other words, the fingerprint-based pharmaceutical composition analysis method may be performed by software or hardware installed in a terminal device or a server device, and the software may be a blockchain platform. The service end includes but is not limited to: a single server, a server cluster, a cloud server or a cloud server cluster, and the like. The server may be an independent server, or may be a cloud server that provides cloud services, cloud databases, cloud computing, cloud functions, cloud storage, network services, cloud communications, middleware services, domain name services, security services, content delivery networks (Content Delivery Network, CDN), and basic cloud computing services such as big data and artificial intelligence platforms.
Referring to fig. 1, a flow chart of a method for analyzing pharmaceutical ingredients according to an embodiment of the invention is shown. In this embodiment, the method for analyzing a pharmaceutical composition based on fingerprint includes:
s1, obtaining target medicines in different batches, and preprocessing the target medicines to obtain test samples of the target medicines.
In the embodiment of the invention, the acquisition of the target drugs in different batches means the collection of the target drugs, the sample collection is the first key step of researching the fingerprint, the collected samples have enough representativeness, and the more and the better the number of the samples are, the more the obtained fingerprint has biological significance.
In detail, the different batches refer to distinguishing the target drugs in terms of variety, medicinal site, origin, harvesting period, origin processing and processing methods, for example: for traditional Chinese medicinal materials with multiple varieties or multiple medicinal parts, a single variety or single medicinal part is fixed, meanwhile, representative sample fingerprint analysis and comparison of different varieties or different medicinal parts are carried out, the commonality and the characteristics of the fingerprint among the varieties or the medicinal parts are found out, the quality of the medicinal material is calibrated by adopting the commonality fingerprint, and the quality of the variety or the medicinal part of the medicinal material and the quality of the medicinal material of the variety or the medicinal part are calibrated by adopting the characteristic fingerprint.
In detail, the pretreatment of the target drug refers to generating an experimental sample of the target drug, for example: cleaning the plants of the target medicine, separately storing roots, stems and leaves, marking the roots of the 1 st plant as W1-1-1, marking the stems as W1-1-2, marking the leaves as W1-1-3, and the like, drying in the shade, crushing, sieving with a 60-mesh sieve for later use, accurately weighing sample powder 1.0 mg, uniformly mixing with KBr in a mortar according to a ratio of 1:50, and tabletting to obtain a test sample of the target medicine.
S2, preparing a plurality of sample solutions of the test samples according to the test samples, and performing attribute configuration on a preset chromatograph according to the sample solutions to obtain the configured chromatograph.
In an embodiment of the present invention, the preparation of the test sample solutions of the plurality of test samples according to the test sample refers to a test sample solution obtained by dissolving the test sample in a solvent, for example: methanol was added to 1.0g of the test sample to dissolve and the volume was set to 25ml, and the solution was filtered through a microporous membrane (pore size: 0.45 μm) to obtain a filtrate as a sample solution.
In detail, the attribute configuration of the preset chromatograph according to the sample solution is to determine attribute parameters of the preset chromatograph according to physicochemical properties of the sample solution, for example: chromatographic column, mobile phase, flow rate, column temperature, detection wavelength, reference wavelength, analysis time, etc.
S3, selecting one of the sample solutions as a target solution, performing multiple verification on the prepared chromatograph according to the target solution, and determining that the chromatograph passing the verification is a standard chromatograph.
In the embodiment of the invention, the multiple verification is used for ensuring the rationality and superiority of chromatographic conditions and the reliability of test results, thereby carrying out the test of instrument precision, test sample stability and experimental method repeatability.
In an embodiment of the present invention, the performing multiple verification on the configured chromatograph according to the target solution includes:
generating a target chromatogram of the target solution according to the target solution and the configured chromatograph;
performing precision verification on the configured chromatograph according to the chromatogram, and determining that the chromatograph which is configured to be completed through the precision verification is a primary verification chromatograph;
performing stability verification on the primary verification chromatograph according to the chromatogram, and determining that the primary verification chromatograph passing the stability verification is a secondary verification chromatograph;
and carrying out repeatability verification on the secondary verification chromatograph according to the chromatogram, and determining that the secondary verification chromatograph passing the repeatability verification is a standard chromatograph.
In detail, the precision verification is to verify the precision of the configured chromatograph; the stability verification refers to examining the stability of the sample solution; the reproducibility verification is to verify the reproducibility of the chromatographic method.
In detail, the repeatability verification may be performed as follows: taking more than 5 parts of samples of the same batch, respectively preparing test sample solutions according to a selected extraction and separation method, and detecting under a selected chromatographic condition to ensure that the RSD of the area ratio of the common peaks to the peaks is less than 3%.
In detail, the performing precision verification on the configured chromatograph according to the chromatogram, determining that the configured chromatograph is a primary verification chromatograph through precision verification, including:
obtaining the peak area of a common peak in the chromatogram, and generating the area ratio of the common peak according to the peak area;
the relative standard deviation of the common peak is calculated using the following relative standard deviation algorithm and the area ratio:
wherein ,
is the relative standard deviation of the common peak, < >>
Is the total of the area ratios, +.>
Is->
The area ratio of the individual said common peaks, < >>
Is the identity of the common peak, +.>
Is the average of the area ratios.
And when the relative standard deviation is smaller than a preset deviation threshold, verifying the configured chromatograph through precision.
In detail, the target solution is sampled for more than 5 times to detect, the RSD of the area ratio of each common peak to peak is less than 3%, and the relative retention time of each common peak is within 1 min.
Further, the common peak is a value obtained by determining a common fingerprint peak (relative retention time, peak area ratio) from the number of peaks, peak value (integrated value), peak position (retention time) and the like given by the chromatogram.
Further, the common peak is determined from the correlation parameters such as the number of peaks, peak value and peak position given by the chromatogram, the integral value of each chromatographic peak is calculated from the chromatogram, and the peak value of the chromatographic peak is determined according to the integral value; calculating retention time of each chromatographic peak from the chromatogram, and determining peak positions of the chromatographic peaks according to the retention time; the integral value and the retention time are used to calculate the relative retention time and peak area ratio to determine the common peak.
In detail, referring to fig. 2, the performing stability verification on the primary verification chromatograph according to the chromatogram, determining that the primary verification chromatograph passing the stability verification is a secondary verification chromatograph, includes:
s21, sequentially combining the chromatograms according to time to obtain a synthetic chromatogram of the chromatogram;
s22, selecting one of characteristic peaks in the synthetic chromatogram as a target characteristic peak, and calculating the relative retention time of the target characteristic peak at different times;
s23, calculating the feature similarity of the target feature peak according to the relative retention time, and when the feature similarity is larger than a preset similarity threshold, verifying the stability by the first-stage verification chromatograph.
In detail, the target solution is taken and detected at different times (0, 1, 2, 4, 8, 12, 24, 36 and 48 hours), the consistency of the relative retention time and the peak area ratio of chromatographic peaks is examined, and the detection time is determined.
S4, performing chromatographic analysis on the sample solution by using the standard chromatograph to obtain test data of the sample solution, and generating a fingerprint of the sample solution according to the test data.
In the embodiment of the invention, sample injection processing is performed on the sample solution, and test data of the sample solution is obtained by using the standard chromatograph, wherein the test data comprises: signals, time, etc.; and performing visual processing on the test data to obtain the fingerprint of the sample solution.
In detail, the overlapping rate, the n strong peak and the characteristic fingerprint peak can be obtained from the fingerprint, wherein the overlapping rate reflects the similarity of the fingerprint, the larger the overlapping rate is, the more similar the fingerprint is, in actual work, a reasonable interval range is defined for the overlapping rate according to specific conditions, the overlapping rate is an important qualitative basis, and reliable evidence is provided for traditional Chinese medicine variety identification; the n strong peaks reflect the relative content of each main component in the traditional Chinese medicine sample, and provide important information and basis for evaluating the quality of the traditional Chinese medicine; the characteristic fingerprint is a fixed peak group composed of a series of characteristic fingerprint peaks, reflects the internal characteristics of the traditional Chinese medicine from the multicomponent angle, and provides more and more detailed information and basis for identifying the varieties of raw medicinal materials or decoction pieces, especially the medicinal materials of different species of the same genus or different species containing the same effective components.
S5, screening out characteristic peaks of the sample solution according to the fingerprint, and determining the components of the target medicament by using a preset reference fingerprint and the characteristic peaks.
In the embodiment of the invention, various interferences inevitably exist in devices such as sampling, changing and the like of an analysis instrument, so that a chemical spectrogram is generally composed of two parts of signal peaks and noise, and therefore, the data processing of noise removal must be carried out on the spectrogram.
In the embodiment of the present invention, the screening the characteristic peak of the sample solution according to the fingerprint includes:
removing noise from the fingerprint to obtain a first-level fingerprint of the fingerprint;
analyzing the overlapped peaks in the primary spectrum to obtain a secondary spectrum of the primary spectrum;
and carrying out standardization treatment on the signal intensity in the secondary spectrum to obtain a standard spectrum of the secondary spectrum, and determining a characteristic peak of the sample solution according to the standard spectrum.
In detail, the fingerprint spectrum data processing is to identify the spectrum peak, so that the peak height, peak position and peak area can be determined, thus the component and content information in the chromatographic analysis sample can be calculated and obtained, and in the aspect of peak area calculation, the turning point can be used for marking the peak starting point and the peak end point, and the peak area between the starting point and the end point can be calculated. However, due to noise, some noise points are also mistakenly identified as a spectral peak, and some spectral peaks are impurity peaks, which should be removed, so that filtering is needed for this case.
In the embodiment of the present invention, the performing noise removal on the fingerprint to obtain a first-level fingerprint of the fingerprint includes:
and removing noise from the fingerprint spectrum by using the following linear filtering algorithm to obtain a primary spectrum of the fingerprint spectrum:
wherein ,
is a dimension +.>
Is>
Is a transposed matrix of the filter coefficient matrix, < >>
Pixel gray matrix of the fingerprint spectrum covered by the filter, < >>
Is a convolution matrix of the fingerprint;
and determining a first-level map of the fingerprint map according to the convolution matrix.
For example: all coefficients of the mean filter are positive numbers in order to keep the output image within the original gray scale range.
In the embodiment of the present invention, referring to fig. 3, the analyzing the overlapping peaks in the primary spectrum to obtain a secondary spectrum of the primary spectrum includes:
s31, determining one of the overlapping peaks in the primary map as a target peak, determining a trough of the target peak according to the target peak, and determining Zuo Feng and a right peak of the target peak according to the trough;
s32, calculating the left area of the left peak according to the left peak height and the bottom left half peak width of the left peak, and calculating the right area of the right peak according to the right peak height and the bottom right half peak width of the right peak;
s33, eliminating peak errors of the overlapped peaks according to the left area and the right area, and obtaining a secondary spectrum of the primary spectrum.
In detail, the fingerprint of the standard chromatograph, which may be a high performance liquid chromatograph, has a case of overlapping peaks due to limited separation capability and various noises of the chromatographic column.
In the embodiment of the invention, because of inconsistent dosage control, experimental conditions, operation methods and the like, the intensity and peak area of fingerprint signals are different, and errors are generated in the next processing, the signal intensity is required to be standardized, and the calibration of the instrument system errors of the chromatographic fingerprint obtained by the same traditional Chinese medicine sample under different experimental conditions is realized.
In the embodiment of the present invention, the normalizing the signal intensity in the secondary spectrum to obtain a standard spectrum of the secondary spectrum includes:
selecting one chromatographic peak in the secondary spectrum one by one as a standard peak, and calculating the standard area of the standard peak according to the signal intensity in the secondary spectrum;
adding the standard areas to obtain the total peak area of the secondary map;
and calculating the normalized area of the standard peak according to the total peak area and the standard area, and carrying out normalization processing on the secondary spectrum according to the normalized area to obtain a standard spectrum of the secondary spectrum.
In detail, the signal strength refers to the magnitude of the response signal, and the summing of the standard areas is to sum the areas according to the addition in the four-rule operation.
Further, the calculating the normalized area of the standard peak according to the total peak area and the standard area is obtained by subtracting the standard area from the total peak area and dividing the standard area by the total peak area.
In detail, the components of the target drug are determined by using a preset reference fingerprint and the characteristic peaks, wherein the components are obtained by calculating the difference degree or the similarity between the characteristic peaks and the peaks in the reference fingerprint, test data of the characteristic peaks can be imported into fingerprint similarity calculation software, after the peaks are selected, a matching template is set, the spectral peaks are automatically matched, then a standard template is set, and spectral peak difference evaluation and overall similarity evaluation are performed.
According to the embodiment of the invention, the target medicines in different batches are obtained, the target medicines are preprocessed to obtain the test sample of the target medicines, so that the target medicines have enough representativeness, the obtained fingerprint has more biological significance, the preset chromatograph is configured according to the sample solution to obtain the configured chromatograph, the error testing time of the subsequent sample solution is saved, the separation efficiency of the sample solution is improved, the configured chromatograph is subjected to multiple verification, the rationality and superiority of chromatographic conditions are ensured, the reliability of test results is ensured, the components of the sample solution are determined based on similarity calculation of a large amount of data on the generated characteristic peaks according to the standard chromatograph and the preset reference fingerprint, the identification accuracy is improved, the identification time is saved, and the problem of low analysis efficiency of medicine components is solved.
Fig. 4 is a functional block diagram of a fingerprint-based pharmaceutical composition analysis device according to an embodiment of the present invention.
The fingerprint-based pharmaceutical composition analysis apparatus 100 of the present invention may be installed in an electronic device. Depending on the functions implemented, the fingerprint-based pharmaceutical composition analysis device 100 may include a test sample module 101, an attribute configuration module 102, a multiple verification module 103, a fingerprint module 104, and a pharmaceutical composition module 105. The module of the invention, which may also be referred to as a unit, refers to a series of computer program segments, which are stored in the memory of the electronic device, capable of being executed by the processor of the electronic device and of performing a fixed function.
In the present embodiment, the functions concerning the respective modules/units are as follows:
the test sample module 101 is configured to obtain target drugs in different batches, and perform pretreatment on the target drugs to obtain a test sample of the target drugs;
the attribute configuration module 102 is configured to prepare a plurality of sample solutions of the test samples according to the test samples, and perform attribute configuration on a preset chromatograph according to the sample solutions to obtain a configured chromatograph;
the multiple verification module 103 is configured to select one of the sample solutions as a target solution, perform multiple verification on the configured chromatograph according to the target solution, and determine that the chromatograph passing the verification is a standard chromatograph;
the fingerprint spectrum module 104 is configured to perform chromatographic analysis on the sample solution by using the standard chromatograph to obtain test data of the sample solution, and generate a fingerprint spectrum of the sample solution according to the test data;
the pharmaceutical composition module 105 is configured to screen out a characteristic peak of the sample solution according to the fingerprint, and determine a composition of the target pharmaceutical by using a preset reference fingerprint and the characteristic peak.
Furthermore, it is evident that the word "comprising" does not exclude other elements or steps, and that the singular does not exclude a plurality. A plurality of units or means recited in the apparatus claims can also be implemented by means of one unit or means in software or hardware. The terms first, second, etc. are used to denote a name, but not any particular order.
Finally, it should be noted that the above-mentioned embodiments are merely for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made to the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention.
Claims (6)
1. A method of pharmaceutical composition analysis, the method comprising:
obtaining target medicines in different batches, and preprocessing the target medicines to obtain test samples of the target medicines;
preparing sample solutions of a plurality of test samples according to the test samples, and performing attribute configuration on a preset chromatograph according to the sample solutions to obtain a configured chromatograph;
selecting one of the sample solutions as a target solution, performing multiple verification on the prepared chromatograph according to the target solution, and determining that the chromatograph passing the verification is a standard chromatograph;
performing chromatographic analysis on the sample solution by using the standard chromatograph to obtain test data of the sample solution, and generating a fingerprint of the sample solution according to the test data;
screening out characteristic peaks of the sample solution according to the fingerprint, and determining the components of the target medicament by using a preset reference fingerprint and the characteristic peaks;
the multiple verification of the configured chromatograph according to the target solution comprises the following steps:
generating a target chromatogram of the target solution according to the target solution and the configured chromatograph;
performing precision verification on the configured chromatograph according to the chromatogram, and determining that the chromatograph which is configured to be completed through the precision verification is a primary verification chromatograph;
performing stability verification on the primary verification chromatograph according to the chromatogram, and determining that the primary verification chromatograph passing the stability verification is a secondary verification chromatograph;
performing repeatability verification on the secondary verification chromatograph according to the chromatogram, and determining that the secondary verification chromatograph passing the repeatability verification is a standard chromatograph;
performing precision verification on the configured chromatograph according to the chromatogram, and determining that the configured chromatograph is a primary verification chromatograph through the precision verification, wherein the primary verification chromatograph comprises:
obtaining the peak area of a common peak in the chromatogram, and generating the area ratio of the common peak according to the peak area;
the relative standard deviation of the common peak is calculated using the following relative standard deviation algorithm and the area ratio:
wherein ,
is the relative standard deviation of the common peak, < >>
Is the total of the area ratios, +.>
Is->
The area ratio of the individual said common peaks, < >>
Is the identity of the common peak, +.>
Is the average of the area ratios;
when the relative standard deviation is smaller than a preset deviation threshold, verifying the configured chromatograph through precision;
the stability verification is performed on the primary verification chromatograph according to the chromatogram, the primary verification chromatograph passing the stability verification is determined to be a secondary verification chromatograph, and the method comprises the following steps:
sequencing and combining the chromatograms according to time sequence to obtain a synthetic chromatogram of the chromatogram;
selecting one of the characteristic peaks in the synthetic chromatogram as a target characteristic peak, and calculating the relative retention time of the target characteristic peak at different times;
and calculating the feature similarity of the target feature peak according to the relative retention time, and when the feature similarity is larger than a preset similarity threshold value, verifying the stability by the primary verification chromatograph.
2. The method according to claim 1, wherein the screening the characteristic peaks of the sample solution according to the fingerprint comprises:
removing noise from the fingerprint to obtain a first-level fingerprint of the fingerprint;
analyzing the overlapped peaks in the primary spectrum to obtain a secondary spectrum of the primary spectrum;
and carrying out standardization treatment on the signal intensity in the secondary spectrum to obtain a standard spectrum of the secondary spectrum, and determining a characteristic peak of the sample solution according to the standard spectrum.
3. The method of claim 2, wherein said noise removing the fingerprint to obtain a first level of the fingerprint comprises:
and removing noise from the fingerprint spectrum by using the following linear filtering algorithm to obtain a primary spectrum of the fingerprint spectrum:
wherein ,
is a dimension +.>
Is>
Is a transposed matrix of the filter coefficient matrix, < >>
Pixel gray matrix of the fingerprint spectrum covered by the filter, < >>
Is a convolution matrix of the fingerprint;
and determining a first-level map of the fingerprint map according to the convolution matrix.
4. The method of claim 2, wherein said analyzing the overlapping peaks in the primary spectrum to obtain a secondary spectrum of the primary spectrum comprises:
determining one of the overlapping peaks in the primary spectrum as a target peak, determining a trough of the target peak according to the target peak, and determining Zuo Feng and a right peak of the target peak according to the trough;
calculating the left area of the left peak according to the left peak height and the bottom left half peak width of the left peak, and calculating the right area of the right peak according to the right peak height and the bottom right half peak width of the right peak;
and eliminating peak errors of the overlapped peaks according to the left area and the right area to obtain a secondary spectrum of the primary spectrum.
5. The method for analyzing pharmaceutical ingredients according to claim 2, wherein the normalizing the signal intensity in the secondary spectrum to obtain a standard spectrum of the secondary spectrum comprises:
selecting one chromatographic peak in the secondary spectrum one by one as a standard peak, and calculating the standard area of the standard peak according to the signal intensity in the secondary spectrum;
adding the standard areas to obtain the total peak area of the secondary map;
and calculating the normalized area of the standard peak according to the total peak area and the standard area, and carrying out normalization processing on the secondary spectrum according to the normalized area to obtain a standard spectrum of the secondary spectrum.
6. A pharmaceutical composition analysis apparatus for realizing the pharmaceutical composition analysis method according to claim 1, characterized in that the apparatus comprises:
the test sample module is used for obtaining target medicines in different batches, and preprocessing the target medicines to obtain test samples of the target medicines;
the attribute configuration module is used for preparing sample solutions of a plurality of test samples according to the test samples, and performing attribute configuration on a preset chromatograph according to the sample solutions to obtain the configured chromatograph;
the multiple verification module is used for selecting one of the sample solutions to be used as a target solution, carrying out multiple verification on the prepared chromatograph according to the target solution, and determining that the chromatograph passing the verification is a standard chromatograph;
the fingerprint spectrum module is used for carrying out chromatographic analysis on the sample solution by utilizing the standard chromatograph to obtain test data of the sample solution, and generating a fingerprint spectrum of the sample solution according to the test data;
and the medicine component module is used for screening out characteristic peaks of the sample solution according to the fingerprint, and determining the components of the target medicine by utilizing a preset reference fingerprint and the characteristic peaks.
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