JP2002340791A - Analysis method and apparatus using spectral data - Google Patents

Abstract

(57) [Summary] An object of the present invention is to provide an analysis method using spectral data that can be easily and accurately analyzed. SOLUTION: The measurement result obtained by irradiating the sample with the measurement light in a state where the sample is kept in a predetermined sample bag which is used for storage of the sample and has light transmittance to the measurement light is obtained. A spectrum acquisition step (S110) for obtaining spectrum data based on the spectrum acquisition step (S110).
110) a filter processing step (S112) for removing the interference fringe component derived from the sample bag previously obtained from the spectrum data of the sample obtained in the sample processing, and a spectrum obtained in the filter processing steps (S112, S114). Analysis step of analyzing the sample using the data (S116)
An analysis method using spectral data, comprising:

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an analysis method using spectral data and an apparatus therefor, and more particularly to an improvement in data processing of spectral data obtained by measuring a sample in a sample.

[0002]

2. Description of the Related Art Conventionally, quantitative and qualitative analysis of pharmaceutical raw materials and the like has been performed using, for example, near infrared spectroscopy. Generally, a sample such as a pharmaceutical raw material is stored in a sample bag such as a plastic bag of polyethylene, for example, except during measurement.

For this reason, at the time of measurement, a sample is taken out of the sample bag used for storage and placed on a sample holder. This is set in a sample chamber of an analyzer such as an infrared spectrophotometer, and measurement is performed. The measured data is processed to obtain spectral data, and the quantitative and qualitative analysis of the sample is performed using the spectral data.

[0004]

By the way, in the above-described method, it is necessary to take out the sample from the sample bag used for storage and to mount it on the holder every time the measurement is performed, so that the measurement becomes complicated. For this reason, there is a strong demand for nondestructive and easy analysis without removing the sample from the sample bag.

[0005] However, if the analysis is performed while the sample is placed in the sample bag used for storage, errors in component concentrations and erroneous determination may occur.

Therefore, conventionally, a method of performing data processing such as smoothing on spectrum data obtained by measuring a sample in a sample bag is considered. However, in this smoothing, information necessary for the sample is obtained. I will lose. For this reason, it has not been adopted as a means for solving the above-mentioned error in component concentration or misdetermination. Further, the cause of the error or the erroneous determination of the component concentration has not been elucidated yet.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned problems of the related art, and an object of the present invention is to provide an analysis method using spectral data that can be easily and accurately analyzed, and an apparatus therefor.

[0008]

As described above, non-destructive measurement can be performed if the measurement is carried out without removing the sample from the sample bag used for storing the sample, but errors in component concentrations and erroneous determinations may occur. May occur.

Therefore, the inventor of the present invention has intensively studied the cause. As a result, strong interference fringes originating from the sample bag overlapped with the sample spectrum data, and this was large compared to the sample spectrum intensity, which caused errors in component concentration and misdetermination. I found out.

That is, a sample bag is schematically illustrated as shown in FIG. In FIG.
Receives the measurement light 12, most of the measurement light 12 becomes the transmitted light 14 because the light transmittance of the bag 10 is high.
6 is irradiated. The diffuse reflection light 18 from the sample 16 is emitted to the outside air 20 of the bag 10.

On the other hand, when the sample bag 10 receives the measurement light 12, a part of the light is reflected at the boundary between the outside air 20 and the bag 10 and at the boundary between the bag 10 and the inside air 22 in some cases. Each of the reflected lights 24 and 26 has an optical path difference depending on the thickness of the bag 10.

When the sample bag 10 receives the measurement light 12, the light transmittance of the bag 10 is high, so that most of the light 12 is transmitted light 14 and a part of the light is inside air 22-.
Some are reflected at the boundary of the bag 10 and at the boundary of the bag 10 and the outside air 20. Each reflected light 28, 30
Has an optical path difference that depends on the thickness of the bag,
An optical path difference between the reflected lights 24 and 26 and an optical path difference between the reflected lights 28 and 30, that is, interference light due to the thickness of the bag are generated.

As a result, interference light is generated as shown in FIG. That is, in the reflected light 24 (28), a light component having a wavelength as shown in FIG. 3A and a light component having the same wavelength in the reflected light 26 (30) are separated by an optical path difference L (= approximately (2 times the thickness), the peak of the light component of the reflected light 24 (28) is located at the valley of the light component of the reflected light 26 (30), and the two cancel each other out. ), It disappears in appearance.

However, as shown in FIG. 1D, in the case of a light component having a wavelength half that of the above-mentioned (A), the reflected light 24 (2
8) and each light component of the reflected light 26 (30) is shifted by one wavelength,
Both peaks and valleys overlap, and amplitude amplification is performed as shown in FIG. This is superimposed on the diffusely reflected light from the sample as an interference fringe component.

Therefore, the optical path difference between the reflected lights 24 and 26,
Various interference fringes occur due to the difference in the optical path of the reflected lights 28 and 30, that is, the difference in the thickness of the bag.

Since such interference fringes are remarkably strong as compared with the diffusely reflected light from the sample, when they are superimposed on the diffusely reflected light from the sample, there is a high possibility that an error in component concentration or erroneous determination will occur.

The present inventor has determined from the spectral data obtained by measuring the sample bag used for storage without removing the sample bag from the sample bag, the frequency component corresponding to the interference fringe component derived from the sample bag. By cutting the sample, it is possible to satisfactorily remove only the interference fringes substantially derived from the sample bag from the spectrum obtained by measuring the sample in the sample bag. As a result, the inventors have found that the above-described errors in component concentrations and erroneous determination can be significantly reduced, and have completed the present invention.

That is, in order to achieve the above object, an analysis method using spectral data according to the present invention comprises a spectrum collecting step, a filtering step, and an analyzing step.
It is characterized by having.

Here, in the spectrum collecting step, the measurement light is transmitted to the sample while the sample is kept in a predetermined sample bag used for storing the sample. Spectral data is obtained based on the measurement results obtained by irradiation.

In the filtering step, interference fringe components derived from the sample bag previously obtained are removed from the spectrum data of the sample obtained in the spectrum collecting step.

In the analyzing step, the sample is analyzed using the spectrum data obtained in the filtering step.

According to another aspect of the present invention, there is provided an analyzer using spectrum data, comprising: a spectrum collecting unit; a library; a filtering unit; and an analyzing unit.

Here, the spectrum collecting means has a light transmitting property with respect to the measurement light, and applies the measurement light to the sample while the sample is kept in a predetermined sample bag used for storing the sample. Spectral data is obtained based on the measurement results obtained by irradiation.

Further, the library stores interference fringe components derived from the sample bag obtained in advance.

The filter processing means removes the interference fringe component derived from the sample bag stored in the library from the spectrum data of the sample obtained by the spectrum collecting means.

The analyzing means analyzes a sample using the spectrum data obtained by the filtering means.

The term "interference fringe component derived from the sample bag" as used herein refers to an interference fringe component obtained by using an empty sample bag, and is the same or the same type as the sample bag into which the sample is placed. Including.

The term "sample bag" as used herein refers to a container used for storing a sample, such as a general measuring cell.
It does not mean a container used only for measurement.

The term "analysis" as used herein includes the case where quantitative or qualitative analysis is performed and the case where both quantitative and qualitative analysis are performed.

[0030]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A preferred embodiment of the present invention will be described below with reference to the drawings. FIG. 3 shows a schematic configuration of an infrared spectrophotometer as an analyzer according to one embodiment of the present invention.

The infrared spectrophotometer 140 shown in FIG. 1 includes a spectrum collecting means 142 and a computer 144.

Here, the spectrum collecting means 142
Are the infrared light source 146, the interferometer 148, and the sample chamber 150.
And a detector 152.

The measuring light 112a from the light source 146
Are modulated by the interferometer 148 and emitted as an interferogram. Measurement light 112 from interferometer 148
b is incident on the sample 116 placed in the sample chamber 150.

The first characteristic feature of the present invention is that the sample 116 is taken out of a predetermined plastic bag (sample bag) 110 used for storing the sample, which has a light transmitting property with respect to the measurement light 112b. That is, the spectral data of the sample was collected in a state of being inserted. For this reason, in the present embodiment, the sample 116 is set in the sample chamber 150 while being kept in the plastic bag 110.

Then, the plastic bag 110
Is a predetermined sample bag having optical transparency to the measurement light 112b, and the measurement light 112b from the interferometer is incident on the sample 116 in the plastic bag 110 placed in the sample chamber 150. Plastic bag 110
The measurement light 118 diffusely reflected by the sample 116 inside is emitted from the plastic bag 110 and is collected by the light collecting mirror 154. Measurement light 118 condensed by condensing mirror 154
Is received by the detector 152, is converted into an electric signal by the detector 152, is amplified by the amplifier 156, is AD-converted by the AD converter 158, and
It is taken in.

The computer 144 includes a CPU 160,
An interferogram storage unit 162 and an unprocessed spectrum storage unit 164 are provided.
The interferogram data from 58 is stored in the interferogram storage unit 162. And the CPU 16
0 is Fourier-transformed on the interferogram data in the interferogram storage unit 162 to obtain spectrum data. This is stored in the unprocessed spectrum storage unit 164.

The computer 144 has a qualitative library 166 storing qualitative information necessary for qualitative processing.
And a quantitative library 168 storing quantitative information required for quantitative determination.

Then, the CPU 160 identifies the sample using the qualitative information of the qualitative library 166, and calculates the component concentration using the quantitative information of the quantitative library 168.

Here, if the analysis is performed using the spectrum data in the unprocessed spectrum storage unit, errors in component concentration and erroneous definiteness occur, so that the spectrum data obtained as described above is usually subjected to smoothing or the like. A method of performing data processing is also conceivable, but the necessary information of the sample is lost.

Therefore, the second characteristic feature of the present invention is that a filter process for cutting a frequency portion corresponding to an interference fringe derived from a sample bag is performed at a stage prior to the analysis using the spectrum as described above. Is that
For this purpose, the present embodiment includes a CPU (filter processing means, analysis means) 160, a library 172, and a processed spectrum storage means 174.

The library 172 stores the interference fringe information derived from a plastic bag previously obtained from an empty plastic bag of the same type under the same spectrum collection conditions as when the spectrum data of the sample was obtained by the spectrum collection means 142. Is stored.

The CPU 160 has a function as a filter processing means, and stores the spectrum data of the sample 116 obtained by the spectrum collecting means 142 in the unprocessed spectrum storage section 164.
The interference fringe information derived from the empty plastic bag 110 stored in the library 172 is removed from the spectrum data of the sample of.

CPU 160 performs an inverse Fourier transform on this, and stores it in processed spectrum storage section 174.

The CPU 160 has a function as an analysis means. The CPU 160 uses the spectrum data stored in the processed spectrum storage unit 174 as information of the qualitative library 166 and the quantitative library 168 to determine the quality of the sample.
A quantitative analysis is performed, and the analysis result is externally output to an external output unit 170 such as a display or a printer.

In this embodiment, the library 1
72 stores not only interference fringe information derived from one type of empty plastic bag but also interference fringe information derived from a plurality of types of empty plastic bags that will be used for each type of bag. I have. And, when filtering,
The CPU 160 of the computer 144 reads the interference fringe information derived from the corresponding type of empty plastic bag from the library 172, and performs the above-described filter processing.

The infrared spectrophotometer 140 according to the present embodiment
Is configured as above, and its operation will be described below with reference to FIG.

First, a spectrum collecting step is performed by the spectrum collecting means and the computer (S110).

Here, in general, at the time of measurement, the sample is taken out of the plastic bag used for storing the sample, and the holder,
Although it is placed in a measurement cell or the like and set in the sample chamber, the measurement becomes complicated.

Therefore, in the present embodiment, the spectrum data of the sample is collected nondestructively while the sample is not taken out of the predetermined plastic bag used for storing the sample.

That is, although this plastic bag is usually used for storing a sample, it is a predetermined sample bag having a light transmitting property with respect to the measuring light. Used for measurement. Then, the measurement light is incident on the sample in the plastic bag. The light diffusely reflected by the sample in the plastic bag is emitted from the plastic bag, collected by the condenser mirror, and received by the detector. The computer performs Fourier transform on the interferogram data from the detector to obtain spectral data.

Here, if the spectrum obtained by measuring the sample in the plastic bag used for storage is used as it is for the analysis, errors in component concentrations and erroneous definiteness may occur. Although a method of performing the above processing is also conceivable, the necessary information of the sample is lost.

Therefore, in this embodiment, as described above, in order to reduce component concentration errors and erroneous determination when spectral data of the sample is collected while the sample is placed in the plastic bag used for storage. The filtering process (S112) is performed on the spectrum data obtained as described above.

That is, in the present embodiment, the interference fringe information derived from the empty plastic bag of the kind to be used is compared with the time when the spectrum data of the sample in the plastic bag is obtained for each kind of the plastic bag. It is obtained in advance under the same spectrum collection conditions, and this is made into a library in a computer library in advance. And C
The PU reads out the interference fringe information from the empty bag of the same type as the plastic bag used for the measurement of the sample from the library and performs the filter processing at the time of the filter processing.

For example, as shown in FIG. 5 (A), spectra I and I in an unprocessed spectrum storage unit obtained by measuring a sample in a plastic bag used for storage are obtained.
From I and III, the interference fringe information derived from an empty plastic bag of the same type previously obtained in the library is removed. Then, when this is subjected to inverse Fourier transform (S114), the processed spectra I ′ and I ′ as shown in FIG.
I 'and III' are obtained.

The processed spectrum data I ', II', and III 'shown in FIG. 6B can substantially cause errors in component concentrations and misdetermination when the sample is measured in a plastic bag. Only the frequency part corresponding to the strong interference fringes derived from the plastic bag has been successfully removed,
The spectrum data accurately reflects the sample information.

In this embodiment, the sample is stored by performing the sample analysis step (S116) using the processed spectrum data in which the frequency portion corresponding to the interference fringe derived from the plastic bag has been cut in this way. Even if the measurement is carried out in the plastic bag used in the above, errors in component concentrations and erroneous determination at the time of analysis can be greatly reduced.

As described above, in this embodiment, since the spectral data of the sample is collected while the sample is placed in the plastic bag used for storing the sample, the analysis can be easily performed without destruction.

Furthermore, in this embodiment, the interference fringes derived from the same type of empty plastic bag are obtained from the spectrum data of the sample obtained by measuring the sample in the plastic bag used for storing the sample. Filter processing is performed to remove components, and the sample is analyzed using the processed spectral data obtained. For this reason, even if the measurement is performed without removing the sample from the plastic bag used for storage to eliminate the complexity of the measurement, the analysis is performed using the processed spectrum that has been subjected to the above-described filter processing. This makes it possible to obtain a non-destructive and accurate analysis result reflecting the sample information.

Further, regardless of the type of the sample, the type of the plastic bag used for storing the sample can be limited to some extent even if there are many same types or different types. From this, the interference fringe component derived from the empty plastic bag is libraryd in a computer library in advance for each type of plastic bag that will be used, and the CPU responds according to the type of bag used for the measurement. By reading out the interference fringe information derived from the empty plastic bag, the above-described filtering can be performed more easily.

For example, in this embodiment, the spectrum data obtained in advance for various standard samples to be detected is stored in the qualitative library of the computer. Then, the CPU searches the qualitative library of the computer for the spectrum of the standard sample having the highest correlation with the shape of the spectrum of the unknown sample in the processed spectrum storage unit, and substitutes the standard sample name of the searched spectrum for the unknown sample. Judge as the sample name and output this to the outside.

Further, the CPU calculates the component concentration based on calibration information (quantitative information) prepared in advance using the spectrum data of the standard sample whose concentration is known in the quantitative library of the computer.

That is, the CPU calculates the component concentration in the sample from the spectrum data in the processed spectrum storage unit by using a multivariate analysis such as a partial regression least squares (PLS) method as shown in FIG. I do.

For example, it is assumed that the components contained in the sample are two components. Each peak wave number, for example, 4880 cm ⁻¹ , 517
The absorbance ratio at 0 cm ^-1 or the like (2 peak ratio) is determined. Then, the ratio of the two peaks is obtained for each concentration, and the linear expression (Y =
A * X + B) to obtain coefficients A and B. This is C
The PU is stored in the quantitative library as calibration information (quantitative information). Here, in the above linear equation, Y is the ratio of two peaks, and X is the concentration of one substance as a reference relative to the other substance.

Then, when performing a quantitative analysis, the CPU obtains a two-peak ratio, for example, at a peak wave number of 4880 cm ⁻¹ , 5170 cm ^−1, etc. from the spectrum data of the processed spectrum storage unit, and calculates the two-peak ratio. The component concentration is calculated by applying to calibration information (quantitative information) representing a calibration curve as shown in FIG. 7 previously obtained in the quantitative library as described above, and this is output to the outside.

As described above, according to the analyzer of the present embodiment, the same spectrum collection is performed from the spectrum data of the sample obtained by nondestructively measuring the sample in the plastic bag used for its storage. The sample is analyzed using the obtained spectral data except for interference fringe components derived from an empty plastic bag obtained in advance under the conditions.

Therefore, in order to eliminate the complexity of the measurement, even if the measurement is carried out while the sample is placed in the plastic bag, the above-described filter processing may cause an error in component concentration or an erroneous determination. The obtained spectrum data of the sample in which only the strong interference fringes derived from the plastic bag used for storage is well cut. Therefore, by using such filtered spectral data, a non-destructive and accurate analysis result can be obtained.

In addition, many plastic bags used for storing samples are of the same type regardless of the type of sample.
Alternatively, even if they are of different types, since several types can be limited, spectral data of a plastic bag that will be used is made into a library in a computer library in advance, and filter processing is performed using the library. Thereby, the filtering process can be performed more easily.

The present invention is not limited to the above embodiment, and various modifications can be made within the scope of the present invention.

For example, in the above-described embodiment, an example has been described in which an interferometer is provided in a stage preceding the sample chamber. However, an interferometer may be provided in a stage subsequent to the sample chamber.

In the above embodiment, an example was described in which spectra were collected by diffuse reflection measurement. However, any measurement method, for example, general reflection and transmission measurement can be used.

In the above-described embodiment, an example in which the infrared region is used as the measurement region has been described. However, the measurement region is not limited to the infrared region, and may be applied to other regions, for example, visible and ultraviolet regions. it can.

Further, in the above-described embodiment, an example in which a plastic bag is used as a sample bag has been described. However, if the sample bag is used for storing a sample and has a light transmitting property with respect to measurement light, the material of the sample bag may be used. , The shape is
Any one can be used.

Furthermore, in the above-described embodiment, the interference fringe information derived from various empty sample bags is stored in a library. From the viewpoint of simplifying the analysis, the above-described library is particularly preferable. The method described above can be applied to obtaining interference fringe information derived from an empty sample bag.

[0074]

As described above, according to the analyzing method using spectral data and the apparatus therefor according to the present invention,
A spectrum collection step (means) for collecting spectrum data in a state where the sample is kept in the sample bag used for storing the sample, and an empty sample bag previously obtained from the spectrum data of the obtained sample. Since a filter processing step (means) for removing interference fringe components derived from the above is provided and the analysis is performed using the filtered spectral data, the analysis of the sample can be performed easily and accurately without destruction.

[Brief description of the drawings]

FIG.

FIG. 2 is an explanatory diagram of a cause of a defect when measurement is performed using a sample bag according to an embodiment of the present invention.

FIG. 3 is an explanatory diagram of a schematic configuration of an analyzer according to an embodiment of the present invention.

FIG. 4 is a flowchart showing a processing procedure of the analyzer shown in FIG. 3;

FIG. 5A is a spectrum data before filtering obtained by the analyzer shown in FIG. 3, and FIG.
7 is an example of spectrum data that has been filtered by the analyzer shown in FIG.

FIG. 6 is an explanatory diagram of a PLS method used for quantitative analysis in the analyzer shown in FIG.

FIG. 7 is an example of a calibration curve used for quantitative analysis by the analyzer shown in FIG. 3;

[Explanation of symbols]

 10, 110 plastic bag (sample bag) 12, 122 measuring light 16, 116 sample 140 infrared spectrophotometer (analyzer) 142 spectrum collecting means 144 computer (filter processing means, analyzing means) 172 library

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Claims (2)

[Claims] 1. A measurement method which has a light-transmitting property with respect to a measurement light and is obtained by irradiating the sample with the measurement light while the sample is kept in a predetermined sample bag used for storing the sample. A spectrum collection step of obtaining spectrum data based on the result; a filter processing step of removing interference fringe components derived from the sample bag obtained in advance from the spectrum data of the sample obtained in the spectrum collection step; An analysis step of analyzing a sample using the spectrum data obtained in the processing step; and an analysis method using the spectrum data. 2. A measurement obtained by irradiating the sample with the measurement light while keeping the sample in a predetermined sample bag used for storing the sample, the sample having the light transmitting property to the measurement light. A spectrum collection unit that obtains spectrum data based on the result; a library that stores interference fringe components derived from the sample bag obtained in advance; and a library from the spectrum data of the sample obtained by the spectrum collection unit. Filter processing means for removing interference fringe components derived from the stored sample bag, and analysis means for analyzing a sample using spectral data obtained by the filter processing means. An analyzer using spectral data.