JP6237510B2 - Chromatograph data processing apparatus, data processing method, and chromatographic analysis system - Google Patents

Description

  The present invention relates to a data processing apparatus, a data processing method, and a chromatographic analysis system for a chromatographic apparatus such as a liquid chromatograph and a gas chromatograph.

  In the chromatograph apparatus, by analyzing a sample, data representing a chromatogram (hereinafter referred to as chromatogram data) having time on the horizontal axis and signal intensity (such as output voltage) on the vertical axis is acquired. In the chromatograph data processing device, a peak appearing in such a chromatogram is detected, a substance corresponding to the peak is identified from the peak position (retention time) with reference to a preset identification table, Further, the concentration and amount of the substance are calculated from the peak height and area.

  In such a data processing apparatus, in general, there is a limit on the size of a signal that can be processed due to restrictions on the hardware of a signal processing circuit including an A / D converter, and a signal having a magnitude greater than or less than the limit is input. Even if it is done, accurate arithmetic processing cannot be executed.

  In addition to the limitations on signal processing, the reliability of detection results varies depending on the signal level of the detector of the chromatographic apparatus. For example, in an ultraviolet-visible spectrophotometer and a photodiode array detector used as a detector for a liquid chromatograph, in general, nonlinearity becomes more prominent as the concentration of a component in a sample increases as shown in FIG. Accuracy deteriorates. Therefore, it is desirable to perform the analysis so that the concentration of the target component of the sample is within a predetermined range (dynamic range).

JP 2006-292641 A

  If the concentration range of the target component contained in the sample is known in advance, in order to ensure that the detected intensity falls within the dynamic range, the sample should be pretreated, such as diluted or concentrated at an appropriate magnification. Is analyzed (see Patent Document 1). However, if the concentration range is not known at all, the setting of the dilution rate and concentration rate of the sample must rely on the experience and intuition of the analyst. Therefore, for inexperienced inexperienced persons, repeat the measurement while changing the dilution rate and concentration rate, or prepare multiple samples with different dilution rates and concentration rates, and perform multiple analyzes It was necessary to determine the concentration of the component.

  A problem to be solved by the present invention is a chromatographic data processing apparatus capable of performing chromatographic analysis by adjusting the concentration of a target component in a sample to an appropriate value without depending on the experience and intuition of an analyst, and A data processing method and a chromatographic analysis system are provided.

The chromatographic data processing apparatus according to the present invention is:
A data processing apparatus for processing three-dimensional data of time, analysis parameters, and signal intensity obtained by a three-dimensional chromatograph executed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, an analysis parameter P1 of the peak top and an analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. Setting means;
b) a calculation means for calculating a ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2 in each time spectrum belonging to the peak;
c) correction value setting means for setting a correction value from the signal intensity ratio of each time calculated by the calculation means;
d) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the peak top analysis parameter P1, Coefficient determining means for determining a concentration adjustment coefficient that, when multiplied by the estimated value, falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph. And
Here, “analysis parameter” means wavelength, m / z (mass-to-charge ratio), or the like.
Further, the range from the predetermined lower limit intensity value to the upper limit intensity value refers to a so-called dynamic range determined from a limit in signal processing and a limit in quantitative accuracy of a detector used for three-dimensional chromatographic analysis.

A chromatographic data processing apparatus according to another aspect of the present invention is provided.
A data processing apparatus for processing three-dimensional data of time, analysis parameters, and signal intensity obtained by a three-dimensional chromatograph executed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, an analysis parameter P1 of the peak top and an analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. Setting means;
b) a calculation means for calculating a ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2 in each time spectrum belonging to the peak;
c) a graphical means showing the relationship between the signal intensity ratio and the time of the spectrum from which the signal intensity ratio was determined;
d) correction value selection means for allowing the user to select one of the signal intensity ratios shown in the figure as a correction value;
e) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the peak top analysis parameter P1, Coefficient determining means for determining a concentration adjustment coefficient that, when multiplied by the estimated value, falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph. And

The chromatographic data processing method according to the present invention comprises:
A method for processing three-dimensional data of time, analysis parameters and signal intensity obtained by a three-dimensional chromatograph performed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, the analysis parameter P1 of the peak top and the analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. ,
b) In the spectrum at each time belonging to the peak, calculate the ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2,
c) Set a correction value from the calculated signal strength ratio of each time,
d) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the analysis parameter P1,
e) A concentration adjustment coefficient is determined such that a value obtained by multiplying the estimated value falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph.

In addition, the chromatographic data processing method according to another aspect of the present invention includes:
A method for processing three-dimensional data of time, analysis parameters and signal intensity obtained by a three-dimensional chromatograph performed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, the analysis parameter P1 of the peak top and the analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. ,
b) In the spectrum at each time belonging to the peak, calculate the ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2,
c) let the display screen show the relationship between the signal intensity ratio and the time of the spectrum from which the signal intensity ratio was determined;
d) Let the user select one of the signal intensity ratios shown on the display screen as a correction value,
e) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the analysis parameter P1,
f) A concentration adjustment coefficient is determined such that a value obtained by multiplying the estimated value falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph.

  The spectrum of a certain component originally has a shape unique to the component, and the shape does not change depending on the concentration. Due to the similarity of the spectrum shapes, the signal intensities of the chromatogram peaks of the analysis parameters belonging to the same peak have a certain relationship with each other. Therefore, using this relationship, the chromatogram peak intensity of the analysis parameter P1 at the peak top can be estimated from the chromatogram peak intensity of another analysis parameter P2 belonging to the same peak. In this case, if the signal strength in the analysis parameter P1 at the peak top or the signal strength in the analysis parameter P2 is out of the dynamic range, etc., if there is a large error in the strength in the analysis parameter P1 or the strength in the analysis parameter P2, The shape of the time spectrum is broken from the original one, and the relationship between the two calculated at that time also deviates from the predetermined relationship. Therefore, a predetermined reference is set in advance, and the relationship in the time domain where the error is small is used.

  For example, when the analysis parameter is a wavelength, in the present invention, first, in the spectrum passing through the peak top of the peak of the target component on the three-dimensional data, the peak top wavelength λ1 and the wavelength λ1 belonging to the peak of the target component Sets another wavelength λ2. The wavelength λ2 is a wavelength whose intensity is within the dynamic range. The wavelength λ1 and the wavelength λ2 are set only when the peak top intensity of the peak of the target component exceeds the upper limit value of the dynamic range, the correction value is calculated as described later, and the peak top intensity is set to the upper limit value. If it does not exceed the value, the quantitative value of the target component may be calculated from the chromatogram peak at the peak top wavelength λ1 by a normal method.

  Next, in the spectrum at each time belonging to the peak of the target component, the ratio of the intensity at the peak top wavelength λ1 and the intensity at the wavelength λ2 is calculated. Then, based on a predetermined selection criterion, the intensity ratio value in the time domain where the intensity at the wavelength λ1 and / or the intensity error at the wavelength λ2 is small is selected as the correction value. Then, by using the correction value and the peak intensity of the target component in the chromatogram of wavelength λ2, the peak intensity in the chromatogram of wavelength λ1 is estimated. Subsequently, when the estimated value of the peak intensity in the chromatogram of the wavelength λ1 is multiplied, a concentration adjustment coefficient is obtained so that the value falls within the dynamic range. This concentration adjustment coefficient reflects the concentration of the target component in the sample used when acquiring the three-dimensional chromatogram. That is, the sample having the concentration adjustment coefficient of 1 has the target component concentration in the sample in an appropriate range. For this reason, the peak intensity of the target component in the three-dimensional chromatogram obtained by the three-dimensional chromatograph executed on the sample falls within the dynamic range.

  On the other hand, a sample having a concentration adjustment coefficient larger than 1 has a concentration of the target component in the sample lower than that suitable for chromatographic analysis, and a sample having a concentration adjustment coefficient smaller than 1 has a target concentration in the sample. The concentration of the component exceeds the appropriate concentration for chromatographic analysis. Therefore, in such a case, a pretreatment for concentrating or diluting the sample at a magnification corresponding to the concentration adjustment coefficient is performed. By doing so, the peak intensity of the target component in the three-dimensional chromatogram obtained for the sample after pretreatment does not exceed the upper limit value of the dynamic range and does not fall below the lower limit value. The value can be determined accurately.

  In this case, based on the concentration adjustment coefficient obtained by the chromatographic data processing device, the chromatographic device automatically performs pre-processing for concentrating / diluting the sample, and performs three-dimensional chromatographic analysis on the pre-processed sample. By doing so, a series of operations from setting the sample to calculating the quantitative value of the target component in the sample can be automated.

That is, a chromatographic analysis system according to the present invention includes a chromatograph device provided with a sample introduction device for introducing a sample into a column, a time obtained by a three-dimensional chromatograph executed by the chromatograph device, analysis parameters, and A system comprising a chromatographic data processing device for processing three-dimensional signal intensity data,
The chromatograph data processing device comprises:
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, an analysis parameter P1 of the peak top and an analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. Setting means;
b) a calculation means for calculating a ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2 in each time spectrum belonging to the peak;
c) correction value setting means for setting a correction value from the signal intensity ratio of each time calculated by the calculation means;
d) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the peak top analysis parameter P1, Coefficient determining means for determining a concentration adjustment coefficient when the estimated value is multiplied within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph;
e) output means for outputting the density adjustment coefficient,
The liquid chromatograph analyzer is
f) a pre-processing unit that pre-processes the sample based on the concentration adjustment coefficient output from the chromatographic data processing apparatus; and a chromatographic analysis execution unit that executes a three-dimensional chromatograph on the pre-processed sample. It is characterized by providing.

  According to the present invention, an index indicating how far a signal intensity obtained by executing a three-dimensional chromatograph on a sample containing a target component deviates from the dynamic range of the three-dimensional chromatograph. 3D chromatographic analysis can be performed with appropriate pretreatment such as dilution / concentration on the sample without relying on the analyst's experience and intuition. Can do.

1 is a schematic configuration diagram of an analysis system including a chromatographic data processing apparatus according to an embodiment of the present invention. The flow-path block diagram for demonstrating operation | movement of the autosampler which comprises the analysis system of a present Example. The schematic flowchart of the data processing in the data processor for chromatographs of a present Example. The contour map which shows the three-dimensional data which the data processor for chromatographs of a present Example acquires. A spectrum along time T1 obtained from the three-dimensional data. A chromatogram along the correction wavelength λ2 obtained from the three-dimensional data. The time-wavelength-intensity three-dimensional graph which shows the processing concept when calculating an intensity ratio. A spectrum at a certain time t belonging to the target peak. Graph showing the relationship between time and intensity ratio, and chromatogram at peak top wavelength λ1 and correction wavelength λ2. Explanatory drawing of the dynamic range in a detector.

  Hereinafter, as an embodiment of the present invention, a chromatographic analysis system including a liquid chromatograph apparatus and a data processing apparatus thereof will be described as an example.

  FIG. 1A is a schematic configuration diagram of an analysis system including a chromatograph data processing apparatus according to the present embodiment. This analysis system includes a liquid feed pump 2 that sucks a mobile phase from a mobile phase container 1 and delivers it at a constant flow rate, and selects and collects samples in a predetermined order from a large number of liquid samples prepared in a rack. The autosampler 3 to be injected into the mobile phase fed by the liquid feed pump 2 and the column 5 into which the liquid sample on the mobile phase is fed are prepared after performing pretreatment such as dilution and concentration according to A column oven 4 for controlling the temperature of the column 5, a photodiode array detector (PDA) 6 for detecting a spectrum of each component in a predetermined wavelength range, a data processing device 7 for processing data output from the PDA 6, It has. The liquid feed pump 2, the autosampler 3, the column oven 4, and the PDA 6 are controlled by the analysis control unit 9 based on instructions from the analysis operation unit 8. The liquid chromatograph apparatus of the present invention is constituted by the liquid feed pump 2, the autosampler 3, the column oven 4, the column 5, the PDA 6, the analysis operation unit 8, the analysis control unit 9, and the like.

  The entity of the data processing device 7 is a general computer including a CPU (Central Processing Unit), a memory, a storage device such as a hard disk and an SSD, and the like. Dedicated data processing software is installed in this computer. By executing this software, the intensity determination unit 71, the wavelength setting unit 72, the intensity ratio calculation unit 73 shown in FIG. Functions of the unit 74, the correction value selection unit 75, the component quantification unit 76, the coefficient determination unit 77, and the like are realized. Further, an operation unit 79 and a display unit 80 which are pointing devices such as a keyboard and a mouse are connected to the data processing device 7.

  FIG. 2 is an example of the configuration of the autosampler 3 and a flow path configuration diagram for explaining the operation. In FIG. 2, an injection valve (high pressure valve) 30 is a rotary 6-port 2-position flow path switching valve having six ports 30a to 30f, and two adjacent ports are selectively connected by a switching operation. The That is, the combination of two connections of solid line or dotted line in FIG. 2A can be switched. On the other hand, the low-pressure valve 31 is a rotary 7-port 6-position valve having seven ports 31a to 31g, and the common port 31g to which the metering pump 32 is connected is one of the other six ports 31a to 31f. The two adjacent ports among the ports 31a to 31f are connected in conjunction with each other. For example, as shown by a solid line in FIG. 2A, when the common port 31g and the port 31b are connected, the ports 31a and 31f are connected.

  A column flow path leading to the column 5 is connected to the port 30b of the injection valve 30, and a mobile phase flow path to which a mobile phase is supplied by the liquid feeding pump 2 is connected to the port 30c. The port 30d is connected to the sample loop 34, and further connected to the port 30a via the needle 36 and the injection port 35. The port 30e and the port 30f are connected to the port 31b and the port 31c of the low pressure valve 31, respectively. A cleaning port 33 is connected to the port 31a of the low pressure valve 31, the port 31e is connected to the metering pump 32, and a cleaning liquid is supplied to the port 31d. The sample rack 38 accommodates a number of vials 39 in which liquid samples, diluents, and the like are stored. The needle 36 can be moved in the horizontal direction and the vertical direction by the moving mechanism 37, and can be inserted into each liquid while moving on the vial 39 and the washing port 33.

  A basic operation sequence at the time of sample introduction in the autosampler 3 will be described. At the time of sample collection, the injection valve 30 and the low pressure valve 31 are switched to the connected state shown by the solid line in FIG. 2A, and the needle 36 is moved onto the vial 39 and inserted into the liquid sample (reference numeral 36). 'Position of). In this state, when the plunger of the metering pump 32 is pulled, the liquid sample is discharged from the vial 39 through the mobile phase (or the cleaning liquid that is the same component) filled in the flow path from the metering pump 32 to the needle 36. The liquid sample is aspirated and retained in the sample loop 34. The collection amount of the liquid sample is equal to the suction amount of the metering pump 32.

  After sampling, the needle 36 is returned to a position on the injection port 35 and connected to the injection port 35. Further, the injection valve 30 is switched to a connection state indicated by a dotted line in FIG. Then, the mobile phase fed from the liquid feed pump 2 is sent to the column 5 through the sample loop 34, the needle 36, and the injection port 35. At this time, the liquid sample previously held in the sample loop 34 is fed into the column 5 together with the mobile phase.

  Cleaning of the needle 36 to which the liquid sample is adhered by such sample suction is performed as follows. That is, the injection valve 30 and the low pressure valve 31 are switched to the connection state indicated by the solid line in FIG. Then, the plunger of the metering pump 32 is pulled and the cleaning liquid is sucked into the syringe. Thereafter, both the injection valve 30 and the low pressure valve 31 are switched to the connection state indicated by the dotted line in FIG. 2A, and when the plunger is pushed and the cleaning liquid is discharged from the metering pump 32, the cleaning liquid is introduced into the cleaning port 33. Then, the excess cleaning liquid is discharged from the drain port of the cleaning port 33. Next, as shown in FIG. 2B, the needle 36 is moved onto the cleaning port 33 and immersed in the cleaning liquid stored in the cleaning port 33. After the needle 36 is cleaned for a certain period of time, the injection port 35 is reached. return.

  The above operation is only the most basic operation. If pretreatment such as concentration or dilution of the target component in the sample or addition of a reagent is added, the operation becomes more complicated. When a series of operations are executed, the operation of each mechanism system such as the valves 30 and 31, the metering pump 32, and the moving mechanism 37 is sequentially executed.

Next, an operation for determining the concentration adjustment coefficient of the liquid sample, which is a characteristic operation of the chromatographic analysis system according to the present embodiment, will be described with reference to the flowchart of FIG.
Prior to the determination of the concentration adjustment factor, in a liquid chromatograph apparatus, the liquid samples in a given vial 39 set in the sample rack 38, chromatographic analysis is performed. That is, the autosampler 3 collects a predetermined amount of liquid sample from a predetermined vial 39 in the sample rack 38 and introduces it into the column 5 of the liquid chromatograph apparatus. The operation from the collection of the liquid sample to the introduction of the liquid sample into the column 5 is as described above. At this time, pretreatment such as diluting or concentrating the liquid sample is not performed.

  When a liquid sample is introduced into the column 5, each component contained in the liquid sample is temporally separated, and a spectrum in a predetermined wavelength range of each component is detected by the PDA 6. This detection data (spectral data) is sequentially sent to the data processing device 7, and as a result, time-wavelength-intensity three-dimensional data as shown in FIG. 4 is obtained (step S1). The intensity determination unit 71 of the data processing device 7 determines whether or not the peak top intensity of the peak of the target component in the three-dimensional data (hereinafter referred to as “target peak”) exceeds a predetermined upper limit Pa. Determine (step S2). The upper limit Pa is a value set in advance in the data processing device 7 in consideration of the dynamic range of the PDA 6 and A / D converter (not shown). Usually, the upper limit value of the dynamic range is used, but a safe value lower than that may be used, or a value slightly higher than that and practically acceptable may be used.

In step S2, when the peak top intensity of the target peak does not exceed the upper limit Pa, the component quantification unit 76 of the data processing device 7 uses a normal method from the chromatogram along the peak top wavelength λ1 of the target peak. The quantitative value (peak area or peak height) of the target component is calculated.
On the other hand, when the peak top intensity of the target peak exceeds the upper limit Pa, even if the quantitative value of the target component is calculated from the chromatogram along the peak top wavelength λ1 of the target peak, it does not become an accurate value. Therefore, the concentration adjustment coefficient of the liquid sample is determined by the following process.

In step S3, in the wavelength range belonging to the target peak of the spectrum in which the wavelength setting unit 72 passes the peak top of the target peak (the spectrum along the time T1 in FIG. 4), the peak top wavelength λ1 and the intensity have a predetermined upper limit. A wavelength (hereinafter referred to as “correction wavelength”) λ2 that is equal to or less than the value Pb and equal to or greater than a predetermined lower limit value Pc is set (FIG. 5). The upper limit value Pb is also a value set in the data processing device 7 in advance based on the upper limit value of the dynamic range of the PDA 6 and the like, similar to the upper limit value Pa. The upper limit value Pa used in step S3 and the upper limit value Pb used in step S4 may be the same or different. In this embodiment, Pa = Pb.
The lower limit value Pc is a value set in advance in the data processing device 7 based on the lower limit value of the dynamic range, and is usually the lower limit value of the dynamic range, but a value slightly higher than that may be used. good.

The intensity ratio calculation unit 73 creates a chromatogram (correction chromatogram) at the correction wavelength λ2 from the three-dimensional data (FIG. 6). In this correction chromatogram, the intensity I ₁ (t) of the wavelength λ1 and the intensity of the correction wavelength λ2 at each time t within the time range [Ta, Tb] (FIGS. 6 and 7) belonging to the target peak. I ₂ (t) is acquired (FIG. 8), and the intensity ratio R (t) is calculated from the ratio as shown in the following equation (step S4).
[Intensity ratio R (t)] = [Intensity I ₁ (t) at wavelength λ1] / [Intensity I ₂ (t) at correction wavelength λ2]

The illustrated unit 74 creates a graph of the intensity ratio R (t) and displays it on the display unit 80. As shown in FIG. 9, the intensity ratio R (t) is constant when at least one of the intensity I ₁ (t) and the intensity I ₂ (t) is out of the dynamic range, and the similarity of the spectrum shape collapses. Deviates from the value. On the other hand, when both the intensity I ₁ (t) and the intensity I ₂ (t) are within the dynamic range, the intensity ratio R (t) has a substantially constant value. Therefore, when both the intensity I ₁ (t) and the intensity I ₂ (t) are within the dynamic range, the similarity between the spectra is ensured most, and the reliability is high. In this embodiment, the correction value selection unit 75 uses the correction value Rs as the median value of the intensity ratio R (t) when both the intensity I ₁ (t) and the intensity I ₂ (t) are within the dynamic range. Is automatically set (step S5).

The coefficient determination unit 77 uses the correction value Rs set in this way to change the peak top intensity PA of the chromatogram along the peak top wavelength λ1 of the target peak to the peak top intensity of the chromatogram of the correction wavelength λ2. A value obtained by multiplying the correction value Rs is calculated (step S6).
Then, when the peak top intensity PA of the target peak is multiplied, the density adjustment coefficient 1 / D is calculated so that the value becomes a value from the lower limit value Pc to the upper limit value Pa of the dynamic range (step S7). In this example, the value obtained by multiplying the peak top intensity PA by the concentration adjustment coefficient 1 / D is not less than three times the lower limit value Pc and the upper limit value so that the peak top intensity of the target peak is surely within the dynamic range. The density adjustment coefficient 1 / D is calculated so that it falls within the correction intensity range of 1/2 or less of Pa. In the density adjustment coefficient 1 / D, “D” corresponds to the dilution rate. In this example, D is an integer for facilitating pretreatment such as dilution / concentration of a liquid sample, and the value obtained by multiplying the peak top intensity PA by 1 / D (PA × (1 / D)). An integer D is obtained so as to be the largest value within the correction intensity range.

  For example, when the dynamic range is 0.4 mAU to 2000 mAU and the peak top intensity PA of the target peak calculated in step S6 is 5633 mAU, PA × (1 / D) is the largest value within the intensity range of 1.2 mAU to 1000 mAU. The integer D becomes “6”. Therefore, the coefficient determination unit 77 determines “1/6” as the density adjustment coefficient.

The density adjustment coefficient 1 / D obtained in step S7 is output from the data processing device 7 to the analysis control unit 9 (step S8). The analysis control unit 9 instructs the autosampler 3 to perform preprocessing according to the value of the density adjustment coefficient 1 / D. Specifically, the autosampler 3 is controlled so as to be introduced into the column 5 after performing a pretreatment for diluting the liquid sample D times with a diluent. Thereafter, the processes of steps S2 to S3 described above are executed. By performing the process of diluting the liquid sample, the peak top intensity PA of the target peak is a range from the lower limit value Pc to the upper limit value Pa (dynamic range). Therefore, the quantitative value of the target component in the liquid sample is calculated by a normal method.
When the quantitative value of the target component is calculated, the data processing device 7 divides the quantitative value by the concentration adjustment coefficient 1 / D. Thereby, the quantitative value of the target component in the liquid sample is obtained.

  In the above embodiment, when the concentration adjustment coefficient 1 / D is obtained, the liquid sample is diluted with the dilution rate D and then introduced into the column 5. However, the amount of the liquid sample introduced into the column 5 is 1 You may change to / D times.

  Moreover, although the said Example demonstrated the case where the peak top intensity | strength of a liquid sample exceeded the upper limit of a dynamic range, this invention is applicable also when it falls below the lower limit of a dynamic range. In this case, the concentration adjustment coefficient 1 / D becomes a value larger than 1 (in other words, D becomes a value smaller than 1), and the liquid sample is concentrated at the concentration rate D as a pretreatment for chromatographic analysis. Alternatively, the amount of the liquid sample introduced into the column is increased by 1 / D times. Thereby, since the peak intensity of the target component obtained when the chromatographic analysis is performed falls within the dynamic range, an accurate quantitative value of the target component in the liquid sample can be obtained.

  The correction value selection unit 75 does not automatically set the correction value Rs, but allows the user to select one intensity ratio from the graph of the intensity ratio R (t) displayed on the display unit 80. May be.

The wavelength setting unit 72 may automatically determine the correction wavelength λ2 based on the three-dimensional data. A method for automatically setting the correction wavelength λ2 is as follows.
・ A spectrum at the retention time T1 of the target peak is acquired.
-For this spectrum, the wavelength for which the intensity value is the “correction wavelength intensity” set in advance by the user on the + side (long wavelength side) or the − side (short wavelength side) of the peak top wavelength λ1 is the correction wavelength. Let λ2 (FIG. 5). The search direction of + or-may be specified by the user in advance, or may be determined by the system (search on the-side in FIG. 5).

  Further, in the above embodiment, it is determined whether or not the peak top intensity of the peak of the target component exceeds the upper limit Pa, and only when the peak top intensity exceeds the upper limit Pa, the processing of steps S3 to S7 is executed. , It may be executed.

DESCRIPTION OF SYMBOLS 1 ... Mobile phase container 2 ... Liquid feed pump 3 ... Autosampler 4 ... Column oven 5 ... Column 6 ... Detector (PDA)
DESCRIPTION OF SYMBOLS 7 ... Data processing apparatus 71 ... Intensity determination part 72 ... Wavelength setting part 73 ... Intensity ratio calculation part 74 ... Illustrated part 75 ... Correction value selection part 76 ... Component determination part 77 ... Coefficient determination part 8 ... Analysis operation part 9 ... Analysis control Portion 30 ... Injection valve 31 ... Low pressure valve 32 ... Metering pump 33 ... Washing port 34 ... Sample loop 36 ... Needle 37 ... Moving mechanism 38 ... Sample rack 39 ... Vial

Claims (7)

In a chromatographic data processing apparatus for processing three-dimensional data of time, analysis parameters and signal intensity obtained by a three-dimensional chromatograph executed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, an analysis parameter P1 of the peak top and an analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. Setting means;
b) a calculation means for calculating a ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2 in each time spectrum belonging to the peak;
c) correction value setting means for setting a correction value from the signal intensity ratio of each time calculated by the calculation means;
d) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the peak top analysis parameter P1, Coefficient determining means for determining a concentration adjustment coefficient that, when multiplied by the estimated value, falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph. A data processing apparatus for chromatographs. In a chromatographic data processing apparatus for processing three-dimensional data of time, analysis parameters and signal intensity obtained by a three-dimensional chromatograph executed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, an analysis parameter P1 of the peak top and an analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. Setting means;
b) a calculation means for calculating a ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2 in each time spectrum belonging to the peak;
c) a graphical means showing the relationship between the signal intensity ratio and the time of the spectrum from which the signal intensity ratio was determined;
d) correction value selection means for allowing the user to select one of the signal intensity ratios shown in the figure as a correction value;
e) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the peak top analysis parameter P1, Coefficient determining means for determining a concentration adjustment coefficient that, when multiplied by the estimated value, falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph. A data processing apparatus for chromatographs. In the chromatograph data processing device according to claim 1 or 2,
A determination means for determining whether or not the peak top intensity of the peak of the target component exceeds a predetermined upper limit;
When the setting means has the peak top intensity exceeding the upper limit, the analysis parameter P1 of the peak top and an analysis parameter whose intensity is not more than a predetermined upper limit intensity value and not less than a predetermined lower limit intensity value. A chromatographic data processing apparatus characterized by being set as the analysis parameter P2. In a chromatographic data processing method for processing time, analysis parameters, and signal intensity three-dimensional data obtained by a three-dimensional chromatograph executed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, the analysis parameter P1 of the peak top and the analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. ,
b) In the spectrum at each time belonging to the peak, calculate the ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2,
c) Set a correction value from the calculated signal strength ratio of each time,
d) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the analysis parameter P1,
e) A chromatographic data process characterized by determining a concentration adjustment coefficient such that a value obtained by multiplying the estimated value falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph. Method. In a chromatographic data processing method for processing time, analysis parameters, and signal intensity three-dimensional data obtained by a three-dimensional chromatograph executed on a sample containing a target component,
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, the analysis parameter P1 of the peak top and the analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. ,
b) In the spectrum at each time belonging to the peak, calculate the ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2,
c) let the display screen show the relationship between the signal intensity ratio and the time of the spectrum from which the signal intensity ratio was determined;
d) Let the user select one of the signal intensity ratios shown on the display screen as a correction value,
e) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the analysis parameter P1,
f) A chromatographic data process characterized by determining a concentration adjustment coefficient such that a value obtained by multiplying the estimated value falls within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph Method. In the chromatograph data processing method according to claim 4 or 5,
Determine whether the peak top intensity of the peak of the target component exceeds a predetermined upper limit intensity value,
When the peak top intensity exceeds the upper limit intensity value, an analysis parameter P2 of the peak top analysis parameter P1 and an analysis parameter whose signal intensity is equal to or lower than a predetermined upper limit intensity value and equal to or higher than a predetermined lower limit intensity value A data processing method for chromatograph, characterized by being set as follows. A chromatographic apparatus having a sample introduction apparatus for introducing a sample into a column, and a chromatograph for processing three-dimensional data of time, analysis parameters, and signal intensity obtained by a three-dimensional chromatograph executed by the chromatograph apparatus In a chromatographic analysis system comprising a data processing device,
The chromatograph data processing device comprises:
a) Based on the three-dimensional data, in the spectrum passing through the peak top of the peak of the target component, an analysis parameter P1 of the peak top and an analysis parameter P2 different from the analysis parameter P1 belonging to the peak are set. Setting means;
b) a calculation means for calculating a ratio of the signal intensity in the analysis parameter P1 to the signal intensity in the analysis parameter P2 in each time spectrum belonging to the peak;
c) correction value setting means for setting a correction value from the signal intensity ratio of each time calculated by the calculation means;
d) Based on the correction value and the peak intensity of the target component in the chromatogram in the analysis parameter P2, obtain an estimated value of the peak intensity of the target component in the chromatogram in the peak top analysis parameter P1, Coefficient determining means for determining a concentration adjustment coefficient when the estimated value is multiplied within a range from a predetermined lower limit intensity value to an upper limit intensity value of the three-dimensional chromatograph;
e) output means for outputting the density adjustment coefficient,
The liquid chromatograph analyzer is
f) a pre-processing unit that pre-processes the sample based on the concentration adjustment coefficient output from the chromatographic data processing apparatus; and a chromatographic analysis execution unit that executes a three-dimensional chromatograph on the pre-processed sample. A chromatographic analysis system comprising:

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