Peak area display device and method, peak area calculation device and method

Abstract

The present invention relates to a peak area display device, which comprises an acquisition unit, a peak area calculation unit and a display device. The acquisition unit acquires measurement data obtained by a chromatograph. The peak area calculation unit suppresses the value of a loss function showing the residual between a chromatogram obtained from the measurement data (MD) and a model function within a prescribed range, and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram. The peak area calculation unit also calculates the maximum or minimum value of the peak area. The display device (display) displays the maximum or minimum value of the peak area calculated by the peak area calculation unit, or displays information obtained by processing the maximum or minimum value of the peak area.

Description

Technical Field

[0001] The present invention relates to a device and method for displaying a peak area of ​​a measured waveform, and a device and method for calculating a peak area. Background Art

[0002] In order to quantitatively and qualitatively analyze the waveform measured by the chromatograph, a model function is fitted to the chromatogram. It is important for the model function to be able to fit the measured waveform with high accuracy. In "PeakFit", HULINKS Co., Ltd., [retrieved on June 4, 2021],<URL:https: / / www.hulinks.co.jp / software / da_visual / peakfit / functions#chorom> In order to quantitatively and qualitatively analyze waveforms measured by a chromatograph, various model functions have been proposed.

[0003] In the management of pharmaceuticals, the content of the main component contained in the pharmaceuticals is required to be above a prescribed amount. In addition, the content of impurities contained in the pharmaceuticals is required to be below a prescribed amount. Therefore, in the analysis of pharmaceuticals, the main component and impurities are quantitatively and qualitatively determined. Summary of the invention

[0004] As mentioned above, it is required to make the fitting of the model function closer to the measured waveform. The purpose is to fit the model function to a reasonable shape representing the measured waveform. In contrast, in the management of impurities of pharmaceuticals, for example, it is more important to manage impurities more appropriately than to fit the model function to a reasonable shape. That is, it is sometimes required to evaluate the upper or lower bound of the peak area rather than to explore a reasonable shape representing the measured waveform.

[0005] An object of the present invention is to provide a method capable of evaluating an upper limit or a lower limit of a peak area of ​​a specific component included in measurement data.

[0006] A peak area display device according to one embodiment of the present invention comprises: an acquisition unit for acquiring measurement data obtained by a chromatograph; a peak area calculation unit for suppressing the value of a loss function showing the residual between a chromatogram obtained from the measurement data and a model function within a specified range, and performing an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and obtaining the maximum or minimum value of the peak area; and a display device for displaying the maximum or minimum value of the peak area obtained by the peak area calculation unit, or displaying information obtained by processing the maximum or minimum value of the peak area.

[0007] A peak area calculation device according to another embodiment of the present invention comprises: an acquisition unit, which acquires measurement data obtained by a chromatograph; and a peak area calculation unit, which suppresses the value of a loss function showing the residual between a chromatogram obtained from the measurement data and a model function within a prescribed range, and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and obtaining the maximum or minimum value of the peak area.

[0008] In addition, the present invention also relates to a peak area display method and a peak area calculation method. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 It is a diagram showing the configuration of the peak area display device according to this embodiment.

[0010] Figure 2 It is a functional block diagram of the peak area display device according to this embodiment.

[0011] Figure 3 This is a diagram showing a chromatogram obtained for a certain sample.

[0012] Figure 4 3 is a diagram showing a chromatogram of the first principal component of the measurement data MD.

[0013] Figure 5 3 is a diagram showing a chromatogram of the second principal component of the measurement data MD.

[0014] Figure 6 3 is a diagram showing a chromatogram of the third principal component of the measurement data MD.

[0015] Figure 7 This is a graph comparing the upper bound estimated area with the least squares estimated area.

[0016] Figure 8 : is a diagram showing the residual error when estimating the upper bound in CH1.

[0017] Fig. 9 : is a diagram showing the residual error when estimating the lower bound in CH1.

[0018] Fig.10 : is a diagram showing the residual error during the least squares estimation in CH1.

[0019] Fig.11 : is a diagram showing the residual error when estimating the upper bound in CH2.

[0020] Fig.12 : is a diagram showing the residual error when estimating the lower bound in CH2.

[0021] Fig.13 : is a diagram showing the residual error during the least squares estimation in CH2.

[0022] Fig.14 : is a diagram showing the residual error when estimating the upper bound in CH3.

[0023] Fig.15 This is a diagram showing the residual error when estimating the lower bound in CH3.

[0024] Fig.16 : is a diagram showing the residual error during least square estimation in CH3.

[0025] Fig.17 : is a flowchart showing a peak area display method according to an embodiment.

[0026] Fig.18 It is a diagram showing an estimation result screen. DETAILED DESCRIPTION

[0027] Next, a peak area display device and method, and a peak area calculation device and method according to embodiments of the present invention will be described with reference to the drawings.

[0028] (1) Configuration of peak area display device

[0029] Figure 1 1 is a diagram showing the configuration of a peak area display device 1 according to the embodiment. The peak area display device 1 according to the present embodiment acquires measurement data MD of a sample obtained by a liquid chromatograph, a gas chromatograph or the like.

[0030] The peak area display device 1 of this embodiment is composed of, for example, a personal computer. Figure 1 As shown, the peak area display device 1 includes a CPU (Central Processing Unit) 11, a RAM (Random Access Memory) 12, a ROM (Read Only Memory) 13, an operation unit 14, a display 15, a storage device 16, a communication interface (I / F) 17, and a device interface (I / F) 18.

[0031] CPU11 performs overall control of the peak area display device 1. RAM12 is used as a work area when CPU11 executes a program. Various data, programs, etc. are stored in ROM13. The operating unit 14 accepts user input operations. The operating unit 14 includes a keyboard and a mouse. The display 15 displays information such as peak fitting results, maximum and / or minimum values ​​of peak areas, etc. The storage device 16 is a storage medium such as a hard disk. The storage device 16 stores program P1, measurement data MD, error α and display data DD. Program P1 performs the processing of obtaining a chromatogram, the processing of fitting a chromatogram model function, the processing of obtaining the maximum and / or minimum values ​​of the peak area, and the processing of displaying the calculated maximum and / or minimum values ​​of the peak area on the display 15. The communication interface 17 is an interface for wired or wireless communication with other computers. The device interface 18 is an interface for accessing a storage medium 19 such as a CD, a DVD, or a semiconductor memory.

[0032] (2) Functional structure of peak area display device

[0033] Figure 2 is a block diagram showing the functional configuration of the peak area display device 1. Figure 2 In the embodiment, the control unit 20 is a functional unit realized by the CPU 11 using the RAM 12 as a work area and executing the program P1. The control unit 20 includes an acquisition unit 21, a peak area calculation unit 22, and an output unit 23. That is, the acquisition unit 21, the peak area calculation unit 22, and the output unit 23 are functional units realized by executing the program P1. In other words, each of the functional units 21 to 23 is a functional unit that the CPU 11 has.

[0034] The acquisition unit 21 inputs the measurement data MD. The acquisition unit 21 inputs the measurement data MD from another computer, an analysis device, etc., for example, via the communication interface 17 . Alternatively, the acquisition unit 21 inputs the measurement data MD stored in the storage medium 19 via the device interface 18 .

[0035] The peak area calculation unit 22 performs a process of fitting a model function to a chromatogram obtained from the measurement data MD, and a process of calculating a maximum value and / or a minimum value of a peak area based on a fitting result of the model function.

[0036] The output unit 23 displays the maximum value and / or minimum value of the peak area calculated by the peak area calculator 22 on the display 15. The output unit 23 also displays information related to the measurement data MD and the fitting result of the model function by the peak area calculator 22 on the display 15.

[0037] The case where the program P1 is stored in the storage device 16 is used as an example for explanation. As another embodiment, the program P1 may also be stored in the storage medium 19 and provided. The CPU 11 may also access the storage medium 19 via the device interface 18, and store the program P1 stored in the storage medium 19 in the storage device 16 or the ROM 13. Alternatively, the CPU 11 may also access the storage medium 19 via the device interface 18, and execute the program P1 stored in the storage medium 19. Alternatively, the CPU 11 may also download the program P1 from a server on the network via the communication interface 17, and store the downloaded program P1 in the storage device 16 or the ROM 13.

[0038] (3) Chromatogram

[0039] Before describing the peak area display method according to the present embodiment, the properties of a chromatogram in which peaks of a plurality of components overlap will be described. Figure 3 This is a diagram showing a chromatogram obtained for a certain sample. In this chromatogram, a peak AP1 for a certain component A appears. Peak AP1 is considered to be a peak that has produced a tail in the peak of component A. In contrast, peak AP2 is a peak that is assumed to have produced no tail in the peak of component A. Residual peak RP is a peak obtained by subtracting peak AP2 from peak AP1. Residual peak RP can be considered to be the tail of the peak of component A, and can also be considered to be a peak derived from peak BP of another component B. In the present embodiment, for example, quantifying the peak of an impurity in an instance where the peak of the impurity overlaps with the peak of the main component of a pharmaceutical is considered a technical problem.

[0040] (4) Peak fitting and peak area estimation

[0041] Next, the peak area display method of the embodiment is described. In the following description, the maximum value of the peak area of ​​impurities contained in the chromatogram is displayed on the display 15 based on the measurement data MD obtained for the pharmaceutical product. In the pharmaceutical product, the content of impurities is required to be less than a specified amount. Therefore, in the peak area display method of the present embodiment, by finding the maximum value of the peak area of ​​impurities contained in the pharmaceutical product, the upper limit of the content of impurities is estimated, thereby providing for the quality evaluation of the pharmaceutical product.

[0042] (4-1) Measurement data in multiple dimensions

[0043] The measurement data MD is data of multiple dimensions acquired for the pharmaceutical product to be analyzed. Here, the case where the measurement data MD is three-dimensional data having elements of retention time direction, spectral direction (frequency direction) and intensity is described as an example. In this case, the measurement data MD is represented by matrix data with retention time direction as rows, spectral direction as columns, and intensity as elements, for example. For example, the measurement data MD is data acquired in a liquid chromatograph equipped with a PDA detector (photodiode array detector).

[0044] (4-2) Dimensional compression of measurement data

[0045] As a pre-processing, the peak area calculation unit 22 performs dimensionality compression on the spectrum of the measurement data MD acquired by the acquisition unit 21. In the present embodiment, the peak area calculation unit 22 performs SVD dimensionality compression using singular value decomposition (SVD: Singular Value Decomposition). In addition, the peak area calculation unit 22 standardizes the intensity of the measurement data MD after dimensionality compression. As a dimensionality compression method, other methods other than SVD dimensionality compression may also be used. Of course, it is also possible to process the measurement data MD in an uncompressed manner without dimensionality compression. Here, each dimension compressed in the spectral direction is referred to as a channel (CH).

[0046] Figures 4 to 6 is a diagram showing measurement data MD reduced to three dimensions by SVD dimensionality compression. Figures 4 to 6 In FIG. 5 , the horizontal axis shows the retention time, and the vertical axis shows the intensity. Figure 4 The chromatogram of channel 1 (CH1) shown is a chromatogram of the first principal component of the measurement data MD. Figure 5 The chromatogram of channel 2 (CH2) shown is a chromatogram of the second principal component of the measurement data MD. Figure 6 The chromatogram of channel 3 (CH3) shown is a chromatogram of the third principal component of the measurement data MD.

[0047] (4-3) Model function

[0048] The peak area calculation unit 22 sets the model function and spectrum showing the shape of the chromatogram to exist as the number of substances, and models the measurement data MD. In addition, the peak area calculation unit 22 treats the baseline of each channel CH1 to CH3 of the measurement data MD as a model in which noise is added to the ideal signal represented by a linear function. As the model function showing the baseline, other polynomials or exponents of the polynomials may also be used. Alternatively, the baseline may also be modeled as an object having information such as the baseline shape and the spectrum, similarly to the peak.

[0049] The peak area calculation unit 22 uses, for example, a GAM model with a second differential constraint as a model function. The model function with a second differential constraint refers to a model function in which a constraint that the second differential (second difference) is non-positive is added to the logarithmic function of the model function. This is because the peak shape of the chromatogram has the characteristic that its logarithmic function is non-positive. In addition, the GAM model refers to a method of fitting a model function to a chromatogram using a generalized additive model (GAM). As a generalized additive model, for example, a smoothing spline is used. However, the model function used by the peak area calculation unit 22 is not particularly limited. The peak area calculation unit 22 may also use the commonly used EMG function and BEMG function as model functions.

[0050] (4-4) Fitting of model function

[0051] The peak area calculation unit 22 fits the above-mentioned model function to the chromatograms of channels CH1 to CH3 by the least square method. Alternatively, the peak area calculation unit 22 may fit the model function to the chromatograms of channels CH1 to CH3 by calculations such as maximum likelihood estimation and posterior probability maximization for the purpose of finding a single solution. That is, the peak area calculation unit 22 fits the model function to the chromatogram for the purpose of minimizing the value of the loss function (LOSS function) showing the residual between the chromatogram and the model function.

[0052] The peak area calculation unit 22 performs a calculation to solve a constrained optimization problem, wherein the peak area of ​​the impurity is maximized under the constraint that the value obtained by adding the error α to the minimum loss value (minimum LOSS) is the range of values ​​that the loss function should take. In the previous peak fitting, the parameters were determined in a way that the loss function took the minimum loss value. According to the peak fitting, the model function is also fitted to a reasonable shape for the peak of the impurity. In contrast, the peak area calculation unit 22 performs peak fitting after adding the error α to the minimum loss value, so that, in terms of fitting, a degree of freedom corresponding to the value of the error α can be provided compared with the past. Under such constraints, the peak area calculation unit 22 performs peak fitting in a way that maximizes the peak area of ​​the impurity.

[0053] The range (prescribed range) that the loss function should take can be set either by user input or by multiplying the observed noise by a prescribed value obtained based on experience or by adding a prescribed value. In addition, the influence of the noise component on the estimated peak height can be calculated as a normal error propagation, and the error range that may be added can be obtained based on the standard error of the estimated peak height. In addition, in this embodiment, the range up to 3σ of the standard error of the peak height is set as the allowable range, and the range obtained by adding the sum of squares of the peak waveform of the +3σ part to the minimum sum of squares is set as the range that the loss function should take.

[0054] like Figure 1 As shown, the error α added to the minimum loss value is stored in the storage device 16. The error α can be any value that is small enough to exist as an estimated error. In the present embodiment, the amount of noise propagated relative to the peak height of the impurity obtained as the least squares solution is considered as error propagation, thereby determining the error α. Specifically, the error α is determined by adding the value obtained by multiplying the standard error of the noise amount several times as the error of the peak height to the loss function. The size of the noise is calculated, for example, based on the signal level around the peak. Alternatively, the size of the noise can also be calculated based on frequency separation, such as by calculating the n-th difference. In this way, the error α is calculated based on the level of the noise extracted from the peak periphery as the processing object area, but the error α can also be calculated based on the area before and after the peak.

[0055] In this way, the peak area calculation unit 22 of the present embodiment performs peak fitting in a manner that maximizes the peak area of ​​the impurity under the constraint that the value obtained by adding the error α to the minimum loss value (minimum LOSS) is the range of values ​​that the loss function should take. Thus, the upper limit of the value that the peak area of ​​the impurity can take can be evaluated. Therefore, effective information can be obtained in the impurity management of pharmaceuticals.

[0056] In the above-mentioned embodiment, in order to manage the impurities of pharmaceuticals, the peak area of ​​the impurities is maximized to fit the model function. In contrast, in order to manage the main components (active ingredients) of pharmaceuticals, it is sufficient to minimize the peak area of ​​the main components to fit the model function. That is, the peak area calculation unit 22 performs a calculation to solve a constrained optimization problem, wherein the peak area of ​​the main component is minimized under the constraint that the value obtained by adding the error α to the minimum loss value is the range of values ​​that the loss function should take. Thus, the lower limit of the value that the peak area of ​​the main component can take can be evaluated. Therefore, effective information can be obtained in the management of the active ingredients of pharmaceuticals.

[0057] (4-5) Experimental results

[0058] Figure 7] is experimental data showing the fitting result of the model function executed by the peak area calculation unit 22. Figure 7 : This is a diagram showing the peaks of the main component X and impurity Y of the pharmaceutical product detected for the measurement data MD. Peaks XPM and YPM are respectively the peaks of the main component X and impurity Y detected by the same method as in the past. That is, peaks XPM and YPM are the results of fitting the model function using the conventional method using the least squares method. Peaks XPU and YPU are respectively the peaks of the main component X and impurity Y detected by the method of this embodiment. That is, peak YPU shows the upper limit of the peak area of ​​impurity Y. Peak YPM is an estimated result of a reasonable peak for impurity Y, whereas peak YPU is an estimated result indicating the upper limit of the peak area of ​​impurity Y.

[0059] Figures 8 to 16 It shows Figures 4 to 6 The experimental data of the residuals of the results of the model function fitting process of this embodiment is performed on the measurement data MD of CH1 to CH3 shown. Figures 8 to 16 In the figure, the horizontal axis shows the retention time and the vertical axis shows the intensity. Figures 8 to 16 In FIG. 1 , the peak shapes of CH1 to CH3 are shown by dotted lines for reference.

[0060] Figure 8 Show Figure 4 The residual between the measurement data MD of CH1 and the peak fitting result based on the upper bound estimation is shown. The upper bound estimation is a fitting process for maximizing the peak area according to the present embodiment. Fig.10 Show Figure 4 The residual of the measured data MD of CH1 and the peak fitting result based on the least square method in the past is shown. From the experimental results, it can be seen that when the upper bound estimation method based on the present embodiment is implemented, the residual does not show a large difference compared with the previous method. Thus, it can be seen that the upper bound estimation method of the present embodiment achieves maximization of the peak area of ​​impurities while maintaining sufficient accuracy in fitting the model function. Fig. 9 is the reference data, showing Figure 4 The residuals of the measurement data MD of CH1 and the peak fitting result based on the lower bound estimation are shown. The lower bound estimation is a fitting process based on the present embodiment to minimize the peak area. Thus, it can be seen that even with the lower bound estimation method, the residuals do not show a large difference.

[0061] Fig.11 Show Figure 5 Shown are the residuals between the measured data MD of CH2 and the peak fitting result based on the upper bound estimation. Fig.13 Show Figure 5The residuals between the measurement data MD of CH1 and the estimation result by the conventional least square method are shown in FIG. As in CH1, it can be seen that the residuals of the measurement data MD of CH2 are not significantly different from those of the conventional method. Fig.12 is the reference data, showing Figure 5 The figure shows the residuals of the measured data MD of CH2 and the peak fitting result based on the lower bound estimation. It can be seen that even with the lower bound estimation method, the residuals do not show a large difference. Figure 14 to Figure 16 The same result was obtained with the measurement data MD of CH3 shown.

[0062] (4-6) Peak area display method

[0063] Next, refer to Fig.17 The peak area display method of this embodiment is described with reference to the flowchart. Fig.17 The flowchart is a process implemented by the CPU 11 executing the program P1. In step S1, the acquisition unit 21 acquires the measurement data MD. The acquisition unit 21 stores the measurement data MD in the storage device 16. As described above, the measurement data MD is data of multiple dimensions.

[0064] Next, in step S2, the peak area calculation unit suppresses the value of the loss function showing the residual between the chromatogram obtained from the measurement data MD and the model function within a specified range, and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram. In the above embodiment, the peak area calculation unit 22 uses the error α stored in the storage device 16 to maximize the peak area of ​​the impurity and perform peak fitting under the constraint that the value obtained by adding the error α to the minimum loss value is the range of values ​​that the loss function should take. Then, in step S3, the peak area calculation unit 22 calculates the maximum or minimum value of the peak area of ​​the target component based on the fitting result of step S2. For example, the peak area calculation unit 22 calculates the maximum value of the peak area of ​​the impurity contained in the pharmaceutical product. As Figure 2 As shown, the peak area calculation unit 22 stores the display data DD including the calculated maximum value and / or minimum value of the peak area in the storage device 16 .

[0065] Then, in step S4 , the output unit 23 acquires the display data DD from the storage device 16 , and displays the display data DD on the display 15 . Fig.18 1 is a diagram showing an example of an estimation result screen 30 displayed on the display 15. The estimation result screen 30 includes a data display area 31, a chromatogram display area 32, and a peak area display area 33. A list of measurement data MD is displayed in the data display area 31. When a certain measurement data MD is selected in the data display area 31, the fitting result of the corresponding model function is displayed in the chromatogram display area 32.

[0066] The peak area display area 33 displays the maximum area (upper limit) and / or the minimum area (lower limit) of the peak displayed in the chromatogram display area 32. The user can confirm the maximum value (upper limit) of the peak area of ​​the impurity contained in the pharmaceutical while confirming the validity of the fitting result of the peak displayed in the chromatogram display area 32. Alternatively, the user can confirm the minimum value (lower limit) of the peak area of ​​the effective ingredient contained in the pharmaceutical.

[0067] (5) Modification

[0068] In the above embodiment, the peak area calculation unit 22 uses the value obtained by adding the error α to the minimum loss value as the constraint condition of the range of values ​​that the loss function should take. As another embodiment, the peak area calculation unit 22 can also solve the loss function minimization problem with regularization, wherein the regularization adds the value of the peak area as a penalty term. In order to maximize the peak area of ​​the impurity, as a penalty term, the peak area can be added as a negative value. In this method, the intensity of the regularization can also be adjusted after obtaining the value of the loss function to what extent.

[0069] In the above embodiment, the measurement data MD is described as 3D data obtained from a liquid chromatograph equipped with a PDA detector. As another example, the measurement data MD may be 3D data obtained in a scanning mode of a liquid chromatograph mass analyzer. In this case, the measurement data MD is 3D data of retention time, mass spectrum, and intensity.

[0070] The embodiment in which the peak area display device 1 displays the maximum value and / or minimum value of the peak area on the display 15 is described. As another embodiment, the device and method of the above embodiment can also be used as a peak area calculation device for calculating the maximum value and / or minimum value of the peak area. The peak area calculation device can, for example, store the maximum value of the peak area of ​​the impurity of the pharmaceutical as the evaluation data of the pharmaceutical in a storage medium.

[0071] In the above embodiment, the maximum value and / or minimum value of the peak area is illustrated as the display data DD. As another example, the display data DD may also be information obtained by processing the maximum value or the minimum value. Specifically, when the maximum value or the minimum value is obtained for more than two peak areas, it may also be the ratio of the maximum value (or minimum value) of the first peak to the maximum value (or minimum value) of the second peak.

[0072] (6) Plan

[0073] Those skilled in the art will appreciate that the above-described multiple exemplary embodiments are specific examples of the following aspects.

[0074] (Item 1)

[0075] A peak area display device according to one embodiment comprises:

[0076] an acquisition unit, which acquires measurement data obtained by the chromatograph;

[0077] a peak area calculation unit that suppresses the value of a loss function showing the residual between the chromatogram obtained from the measurement data and the model function within a specified range and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram to obtain the maximum value or minimum value of the peak area;

[0078] The display device displays the maximum value or the minimum value of the peak area calculated by the peak area calculation unit, or displays information obtained by processing the maximum value or the minimum value of the peak area.

[0079] According to this peak area display device, it is possible to evaluate the upper limit or the lower limit of the peak area of ​​a specific component included in the measurement data.

[0080] (Item 2)

[0081] Alternatively, in the peak area display device described in item 1,

[0082] The measurement data is data obtained by analyzing a pharmaceutical product, and the peak area calculation unit obtains a maximum value of a peak area of ​​an impurity contained in the pharmaceutical product.

[0083] Impurities contained in pharmaceuticals can be managed, thereby providing information useful for evaluating the performance of pharmaceuticals.

[0084] (Item 3)

[0085] Alternatively, in the peak area display device described in item 1 or 2,

[0086] The optimization operation includes an operation for solving a constrained optimization problem, wherein the peak area is maximized or minimized under the constraint that a value obtained by adding a predetermined value to a minimum loss value is a range of values ​​that the loss function should take.

[0087] By providing a range of values ​​that the loss function should take, it is possible to maximize or minimize the peak area while providing a degree of freedom for the accuracy of peak fitting.

[0088] (Item 4)

[0089] Alternatively, in the peak area display device described in item 1 or 2,

[0090] The optimization operation includes an operation of solving a loss function minimization problem with regularization, wherein the regularization uses the value of the peak area as a penalty term.

[0091] Peak fitting can be performed while maximizing or minimizing peak areas.

[0092] (Item 5)

[0093] In the peak area display device according to any one of items 1 to 4,

[0094] The loss function includes a function for obtaining the residual between the chromatogram and the model function by a least square method.

[0095] Ability to fit a model function to the chromatogram.

[0096] (Item 6)

[0097] In the peak area display device according to any one of items 1 to 4,

[0098] The loss function includes a function for obtaining a residual between the chromatogram and the model function by maximum likelihood estimation and posterior probability maximization.

[0099] Ability to fit a model function to the chromatogram.

[0100] (Item 7)

[0101] Another embodiment of the peak area calculation device comprises:

[0102] an acquisition unit, which acquires measurement data obtained by the chromatograph;

[0103] The peak area calculation unit suppresses the value of the loss function showing the residual between the chromatogram obtained from the measurement data and the model function within a specified range, and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and obtaining the maximum or minimum value of the peak area.

[0104] According to this peak area calculation device, it is possible to acquire the upper limit or the lower limit of the peak area of ​​a specific component included in the measurement data.

[0105] (Item 8)

[0106] Alternatively, in the peak area calculation device described in item 7,

[0107] The measurement data is data obtained by analyzing a pharmaceutical product, and the peak area calculation unit obtains a maximum value of a peak area of ​​an impurity contained in the pharmaceutical product.

[0108] Impurities contained in pharmaceuticals can be managed, thereby providing information useful for evaluating the performance of pharmaceuticals.

[0109] (Item 9)

[0110] Another method for displaying peak areas includes:

[0111] A process for acquiring measurement data obtained by a chromatograph;

[0112] A step of suppressing the value of a loss function showing the residual between a chromatogram obtained from the measurement data and a model function within a prescribed range, and performing an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and finding the maximum or minimum value of the peak area;

[0113] A step of displaying the maximum value or the minimum value of the peak area, or displaying information obtained by processing the maximum value or the minimum value of the peak area.

[0114] According to this peak area display method, it is possible to evaluate the upper limit or lower limit of the peak area of ​​a specific component included in the measurement data.

[0115] (Item 10)

[0116] Another method for calculating the peak area includes:

[0117] A process for acquiring measurement data obtained by a chromatograph;

[0118] The value of the loss function showing the residual between the chromatogram obtained from the measurement data and the model function is suppressed within a specified range, and an optimization operation is performed to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and finding the maximum or minimum value of the peak area.

[0119] According to this peak area calculation method, it is possible to obtain the upper limit or lower limit of the peak area of ​​a specific component included in the measurement data.

Claims

1. A peak area display device, characterized in that: have: an acquisition unit, which acquires measurement data obtained by the chromatograph; a peak area calculation unit that suppresses the value of a loss function showing the residual between the chromatogram obtained from the measurement data and the model function within a specified range and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram to obtain the maximum value or minimum value of the peak area; a display device for displaying the maximum value or the minimum value of the peak area obtained by the peak area calculation unit, or displaying information obtained by processing the maximum value or the minimum value of the peak area, The measurement data is data obtained by analyzing and processing the pharmaceutical product. The peak area calculation unit performs an optimization operation to maximize the peak area of ​​the impurities contained in the pharmaceutical or minimize the peak area of ​​the main component, and obtains the maximum value of the peak area of ​​the impurities or the minimum value of the peak area of ​​the main component. The peak of the impurity overlaps with the peak of the main component of the pharmaceutical.

2. The peak area display device according to claim 1, characterized in that: The optimization operation includes an operation for solving a constrained optimization problem, wherein the peak area is maximized or minimized under the constraint that a value obtained by adding a predetermined value to a minimum loss value is a range of values ​​that the loss function should take.

3. The peak area display device according to claim 1, characterized in that: The optimization operation includes an operation of solving a loss function minimization problem with regularization, wherein the regularization uses the value of the peak area as a penalty term.

4. The peak area display device according to claim 1, characterized in that: The loss function includes a function for obtaining the residual between the chromatogram and the model function by a least square method.

5. The peak area display device according to claim 1, characterized in that: The loss function includes a function for obtaining a residual between the chromatogram and the model function by maximum likelihood estimation and posterior probability maximization.

6. A peak area calculation device, characterized in that: have: an acquisition unit, which acquires measurement data obtained by the chromatograph; a peak area calculation unit that suppresses the value of a loss function showing the residual between the chromatogram obtained from the measurement data and the model function within a specified range and performs an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram to obtain the maximum value or minimum value of the peak area, The measurement data is data obtained by analyzing and processing the pharmaceutical product. The peak area calculation unit performs an optimization operation to maximize the peak area of ​​the impurities contained in the pharmaceutical or minimize the peak area of ​​the main component, and obtains the maximum value of the peak area of ​​the impurities or the minimum value of the peak area of ​​the main component. The peak of the impurity overlaps with the peak of the main component of the pharmaceutical.

7. A peak area display method, characterized in that: include: A process for acquiring measurement data obtained by a chromatograph; A step of suppressing the value of a loss function showing the residual between a chromatogram obtained from the measurement data and a model function within a prescribed range, and performing an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and finding the maximum or minimum value of the peak area; a step of displaying the maximum value or the minimum value of the peak area, or displaying information obtained by processing the maximum value or the minimum value of the peak area, The measurement data is data obtained by analyzing and processing the pharmaceutical product. The step of finding the maximum or minimum value of the peak area comprises performing an optimization operation to maximize the peak area of ​​the impurities contained in the pharmaceutical or to minimize the peak area of ​​the main component, thereby finding the maximum value of the peak area of ​​the impurities or the minimum value of the peak area of ​​the main component. The peak of the impurity overlaps with the peak of the main component of the pharmaceutical.

8. A method for calculating peak area, characterized in that: include: A process for acquiring measurement data obtained by a chromatograph; The step of suppressing the value of a loss function showing the residual between a chromatogram obtained from the measurement data and a model function within a predetermined range and performing an optimization operation to maximize or minimize the peak area, thereby fitting the model function to the chromatogram and finding the maximum or minimum value of the peak area, The measurement data is data obtained by analyzing and processing the pharmaceutical product. The step of finding the maximum or minimum value of the peak area comprises performing an optimization operation to maximize the peak area of ​​the impurities contained in the pharmaceutical or to minimize the peak area of ​​the main component, thereby finding the maximum value of the peak area of ​​the impurities or the minimum value of the peak area of ​​the main component. The peak of the impurity overlaps with the peak of the main component of the pharmaceutical.

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