Mass spectrometry apparatus, method for evaluating and calibrating the same, method for analyzing sample, and reagent

Abstract

The present invention provides a quality analysis device, an evaluation and calibration method thereof, an analysis method, and a reagent. The evaluation method of the quality analysis device includes: performing quality analysis on an ester of phthalic acid using the quality analysis device to detect a plurality of ions generated by dissociation of the ester of phthalic acid; and obtaining information on whether the quality analysis device is in a state suitable for analysis based on the intensity ratio of the plurality of detected ions.

Description

Technical Field

[0001] The present invention relates to an evaluation method for a mass spectrometry device, a calibration method for a mass spectrometry device, an analysis method, a mass spectrometry device, and a reagent for mass spectrometry. Background Art

[0002] A large number of chemical substances are produced and utilized. Some chemical substances are restricted due to being harmful to humans or the environment, etc. For example, phthalates are used as plasticizers for resins (see Non-Patent Document 1), but some of them are restricted in Japan, the United States, China, etc., and after 2019, they will be restricted by the Restriction of Hazardous Substances (RoHS) Directive in Europe. Thus, the types of chemical substances that may become analysis targets increase, and sometimes attempts are made to simultaneously measure a large number of components, and it becomes important to accurately measure the components of the analysis target.

[0003] In the analysis using a mass spectrometry device, depending on the type or state of the device, there are cases where different mass spectra are obtained even when analyzing the same compound. Therefore, a first standard substance for mass calibration is measured, and mass calibration (calibration of the horizontal axis of the mass spectrum) is performed using a calibration program. Further, in order to correct for the unevenness of the intensity depending on the cracking conditions or m / z, a second standard substance is analyzed to confirm whether the relative intensity between the peaks of the mass spectrum is within an appropriate range. As the second standard substance, perfluorotributylamine (PFTBA) or decafluorotriphenylphosphine (DFTPP) is known (see Non-Patent Document 2).

[0004] [Prior Art Documents]

[0005] [Non-Patent Documents]

[0006] Non-Patent Document 1: Jeilani YA, Cardelino BH, Ibeanusi VM; "Density functional theory and mass spectrometry of phthalate fragmentations mechanisms: modeling hyperconjugated carbocation and radical cation complexes with neutral molecules", Journal of the American Society for Mass Spectrometry, (USA), Springer-Verlag, August 11, 2011, Volume 22, 1999, Digital Object Identifier (doi): 10.1007 / s13361-011-0215-8

[0007] [Non-Patent Document 2] United States Environmental Protection Agency, "Method 625: Base / Neutrals and Acids", [online], 1984, United States Environmental Protection Agency, [retrieved September 18, 2018], Internet (https: / / www.epa.gov / sites / production / files / 2015-10 / documents / method_625_1984.pdf#search=%27method+625%27) Summary of the Invention

[0008] [Problems to be Solved by the Invention]

[0009] The structures of PFTBA or DFTPP are different from those of chemical substances such as phthalic acid esters. Therefore, there is a situation where, even though it is judged that calibration has been correctly performed in the evaluation of a mass spectrometer using PFTBA or DFTPP, in fact, the mass spectrometer is not suitable for the analysis of the said chemical substances.

[0010] [Technical Means for Solving the Problems]

[0011] According to a first aspect of the present invention, an evaluation method of a mass analyzer includes: performing mass analysis on an ester of phthalic acid using the mass analyzer to detect a plurality of ions generated by dissociation of the ester of phthalic acid; and obtaining information on whether the mass analyzer is in a state suitable for analysis based on a ratio of intensities of the detected plurality of ions.

[0012] According to a second aspect of the present invention, preferably: in the evaluation method of the mass analyzer according to the first aspect, the information is obtained based on a plurality of the ratios of intensities between three or more of the detected ions.

[0013] According to a third aspect of the present invention, preferably: in the evaluation method of the mass analyzer according to the first or second aspect, the ester of phthalic acid is an ester of an ortho-isomer of phthalic acid.

[0014] According to the fourth aspect of the present invention, preferably: in the evaluation method of the mass analysis device according to any one of the first to third aspects, the esters of phthalic acid are selected from the group consisting of diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), di-n-octhyl phthalate (DNOP), di-iso-nonyl phthalate (DINP), diisodecyl phthalate (DIDP), mono-(2-ethylhexyl) phthalate, dimethyl phthalate (DMP), diethyl phthalate (DEP), dipropyl phthalate, bis(2-methoxyethyl) phthalate, bis(2-butoxyethyl) phthalate, n-pentyl isopentyl phthalate, dipropylheptyl phthalate, di-n-pentyl phthalate (DPENP), di-iso-pentyl phthalate (DPENP), di-n-hexyl phthalate (DHEXP), di-iso-hexyl phthalate, dicyclohexyl phthalate (DCHP), dibenzyl phthalate, diheptyl phthalate, di-iso-heptyl phthalate, dinonyl phthalate, didecyl phthalate, di-undecyl phthalate, di-iso-undecyl phthalate, and di-iso-tridecyl phthalate.

[0015] According to the fifth aspect of the present invention, preferably: in the evaluation method of the mass analysis device according to the fourth aspect, the ester of phthalic acid is di-(2-ethylhexyl) phthalate (DEHP).

[0016] According to the sixth aspect of the present invention, preferably: in the evaluation method of the mass analysis device according to any one of the first to fifth aspects, the plurality of detected ions include ions corresponding to peaks in the range where the m / z value is 148 or more and 150 or less.

[0017] According to the seventh aspect of the present invention, preferably, in the evaluation method of the mass analyzer of the sixth aspect, it is determined whether the mass analyzer is in a state suitable for the analysis based on whether the ratio of the intensity of a specified peak to the intensity of a peak in the range of 148 or more and 150 or less in terms of m / z value among the peaks corresponding to the detected multiple ions is within a specified range.

[0018] According to the eighth aspect of the present invention, preferably, in the evaluation method of the mass analyzer of the seventh aspect, the phthalic acid ester is bis(2-ethylhexyl) phthalate (DEHP), and the specified peak is at least one of a first peak in the range of 278 or more and 280 or less in terms of m / z value, a second peak in the range of 166 or more and 168 or less, a third peak in the range of 112 or more and 114 or less, a fourth peak in the range of 70 or more and 72 or less, and a fifth peak in the range of 56 or more and 58 or less. The specified range in the case of the first peak is 5% or more and 15% or less, the specified range in the case of the second peak is 33% or more and 48% or less, the specified range in the case of the third peak is 8% or more and 16% or less, the specified range in the case of the fourth peak is 17% or more and 30% or less, and the specified range in the case of the fifth peak is 17% or more and 44% or less.

[0019] According to the ninth aspect of the present invention, preferably, in the evaluation method of the mass analyzer according to any one of the first to eighth aspects, the phthalic acid ester is dissociated by electron ionization, positive ion chemical ionization, negative ion chemical ionization, atmospheric pressure chemical ionization, or collision-induced dissociation.

[0020] According to the tenth aspect of the present invention, preferably, in the evaluation method of the mass analyzer according to any one of the first to ninth aspects, it includes outputting a notification when the mass analyzer is not in a state suitable for the analysis.

[0021] According to the eleventh aspect of the present invention, a calibration method for a mass analyzer includes: evaluating the mass analyzer by the evaluation method of the mass analyzer according to any one of the first to tenth aspects; and calibrating the mass analyzer based on the evaluation.

[0022] According to the twelfth aspect of the present invention, an analysis method includes: evaluating the mass analyzer by the evaluation method of the mass analyzer according to any one of the first to tenth aspects; and performing an analysis using the mass analyzer.

[0023] According to the thirteenth aspect of the present invention, preferably, in the analysis method of the twelfth aspect, based on the intensity ratio of the detected multiple ions, the data obtained by the analysis is corrected.

[0024] According to the fourteenth aspect of the present invention, a mass spectrometry device includes: a mass analysis unit that performs mass analysis on an ester of phthalic acid and detects multiple ions generated by dissociation of the ester of phthalic acid; and an information acquisition unit that acquires information on whether the mass analysis unit is in a state suitable for analysis based on the intensity ratio of the detected multiple ions.

[0025] A mass analysis reagent according to the fifteenth aspect of the present invention includes an ester of phthalic acid and is used to evaluate a mass spectrometry device based on the intensity ratio of multiple ions generated by dissociation of the ester of phthalic acid obtained by mass analysis.

[0026] [Effects of the Invention]

[0027] According to the present invention, it is possible to correctly evaluate whether a mass spectrometry device is in a state suitable for analyzing chemical substances such as esters of phthalic acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 FIG. is an example of a mass spectrum obtained by dissociating bis(2-ethylhexyl) phthalate (DEHP) schematically.

[0029] Figure 2 FIG. is a schematic diagram showing the configuration of a mass spectrometry device according to an embodiment.

[0030] Figure 3 FIG. is a flowchart showing the process of an analysis method according to an embodiment.

[0031] [Description of Reference Numerals]

[0032] 1: Mass spectrometry device

[0033] 10: Gas chromatograph

[0034] 12: Sample introduction unit

[0035] 14: Separation column

[0036] 15: Sample gas introduction tube

[0037] 30: Mass analysis unit

[0038] 33: Ionization unit

[0039] 35: Mass separation unit

[0040] 36: Detection unit

[0041] 40: Information Processing Unit

[0042] 44: Output Unit

[0043] 50: Control Unit

[0044] 52: Data Processing Unit

[0045] 53: Output Control Unit

[0046] 100: Measurement Unit

[0047] 521: Mass Spectrum Generation Unit

[0048] 522: Ratio Calculation Unit

[0049] 523: Judgment Unit

[0050] 530: Notification Unit

[0051] In: Ion. Detailed Implementation Modes

[0052] Hereinafter, embodiments for implementing the present invention will be described with reference to the drawings. In the following embodiments, "phthalate ester" refers to an ester of the ortho-form of phthalic acid, and "ester of phthalic acid" refers to all esters of the ortho-form, meta-form, and para-form of phthalic acid.

[0053] - First Embodiment -

[0054] In the evaluation method of the mass analyzer in this embodiment, after performing mass calibration of the mass analyzer using a first reference material, information on whether the mass analyzer is in a suitable state for analyzing a substance to be analyzed is obtained using a second reference material containing an ester of phthalic acid.

[0055] (Regarding the reference material)

[0056] Regarding the first reference material, as long as the m / z of the peak detected corresponding to the first reference material is known, there is no particular limitation, and a known mass calibration reagent or the like can be used. As the first reference material, an ester of phthalic acid can also be used. If the first reference material is the same compound as the ester of phthalic acid used in the second reference material described later, calibration based on the first reference material and evaluation based on the second reference material can be performed simultaneously, which is therefore preferable. In mass calibration, multiple different first reference materials with known m / z are detected by mass analysis, and calibration data such as a calibration curve representing the deviation between the detected value and the actual value is generated.

[0057] The second reference material contains esters of phthalic acid, preferably phthalate (ortho isomer). The reason is that phthalates have been pointed out to be harmful and there is a high necessity to be an analysis target. If the compound to be analyzed is similar in structure to the second reference material, the evaluation of the mass analysis device can be performed more accurately.

[0058] The second reference material is more preferably a phthalate represented by the following formula (1), in which R1 and R2 are each independently an alkyl group or an aryl group having 20 or less carbon atoms. Currently, most phthalates used for plasticizers and the like have 12 or less carbon atoms. If they are similar in structure when these are used as analysis targets, the evaluation can be performed more accurately. Therefore, the second reference material is more preferably a phthalate represented by the following formula (1), in which R1 and R2 are each independently an alkyl group or an aryl group having 12 or less carbon atoms.

[0059] [Chemical formula 1]

[0060]

[0061] From the same viewpoint, the second reference material preferably contains a compound selected from diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), diisononyl phthalate (DINP), diisodecyl phthalate (DIDP), mono(2-ethylhexyl) phthalate, dimethyl phthalate (DMP), diethyl phthalate (DEP), dipropyl phthalate, bis(2-methoxyethyl) phthalate, bis(2-butoxyethyl) phthalate, n-pentyl isopentyl phthalate, dipropylheptyl phthalate, di-n-pentyl phthalate (DPENP), diisopentyl phthalate (DPENP), di-n-hexyl phthalate (DHEXP), diisohexyl phthalate, dicyclohexyl phthalate (DCHP), dibenzyl phthalate, diheptyl phthalate, diisoheptyl phthalate, dinonyl phthalate, didecyl phthalate, diundecyl phthalate, diisoundecyl phthalate, and diisotridecyl phthalate.

[0062] The second reference substance is preferably a compound selected from diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP). The reason is that these compounds have become restricted substances in the United States, Europe, etc., and there is a high necessity for them to be the analysis targets. If the compound to be analyzed is structurally similar to the second reference substance, calibration can be performed more accurately. From the same perspective, the second reference substance is further preferably DEHP, which is widely used as a representative general plasticizer.

[0063] Table 1 is a table showing the chemical formulas of DIBP, DBP, BBP, DEHP, DNOP, DINP, and DIDP. In Table 1, "M.W." represents the molecular weight.

[0064] [Table 1]

[0065]

[0066] In the evaluation of a mass analyzer using the second reference substance, fragment ions (hereinafter simply referred to as fragment ions) obtained by detecting the dissociation of the second reference substance through mass analysis are detected, and a mass spectrum showing peaks corresponding to the fragment ions is generated. Based on whether the ratio (hereinafter referred to as the intensity ratio) of the intensity of a specified peak (hereinafter referred to as the comparison target peak) to the intensity of the peak serving as the reference (hereinafter referred to as the reference peak) among the peaks corresponding to the multiple detected fragment ions is within a specified range (hereinafter referred to as the allowable range), it is determined whether the mass analyzer is in a state suitable for analysis.

[0067] Figure 1 is a diagram schematically showing an example of a mass spectrum obtained by dissociating DEHP. In most phthalates, in the mass spectrum showing fragment ions, the peak corresponding to m / z 149 is detected as the most prominent peak. Therefore, it is preferable to use the peak corresponding to m / z 149 as the reference peak. In Figure 1 shows the chemical formula of the fragment ion f0 corresponding to this reference peak. The reference peak can be set as a peak with an m / z value in the range of 148 or more and 150 or less in consideration of the unevenness of measurement, and is preferably set as the peak with the maximum intensity detected within this range. Here, the "detected intensity" is a value representing the magnitude of the detection signal corresponding to the fragment ion, and is quantified by the maximum peak intensity or peak area, etc.

[0068] As the peak of the comparison object, preferably, in the mass spectrum representing fragment ions, one or more peaks with higher detected intensities are selected from the peaks obtained by removing the reference peak.

[0069] When DEHP is used as the second reference substance, the peak of the comparison object is preferably at least one of the first peak in the range of m / z values of 278 or more and 280 or less, the second peak in the range of 166 or more and 168 or less, the third peak in the range of 112 or more and 114 or less, the fourth peak in the range of 70 or more and 72 or less, and the fifth peak in the range of 56 or more and 58 or less. The peak with the highest detected intensity among the peaks in these respective ranges can be set as the peak of the comparison object. In Figure 1 it shows the chemical formulas of the fragment ions f1 and f2 corresponding to the first peak and the second peak, respectively. The first peak, the second peak, the third peak, the fourth peak, and the fifth peak are the peaks corresponding to m / z 279, 167, 113, 71, and 57, respectively.

[0070] Preferably, the allowable range in the case of the first peak is 5% or more and 15% or less, the allowable range in the case of the second peak is 33% or more and 48% or less, the allowable range in the case of the third peak is 8% or more and 16% or less, the allowable range in the case of the fourth peak is 17% or more and 30% or less, and the allowable range in the case of the fifth peak is 17% or more and 44% or less.

[0071] In addition, the selection of the reference peak and the peak of the comparison object, their numbers, and the allowable range can be appropriately set based on the mass spectrum representing fragment ions obtained when performing mass analysis on the second reference substance used, and are not limited to the above examples.

[0072] (Regarding the compound to be analyzed)

[0073] The compound to be analyzed is not particularly limited. An appropriate phthalic acid ester can be selected as the second reference substance according to the m / z of the peak corresponding to the compound to be analyzed. The compound to be analyzed is preferably a phthalic acid ester, more preferably a phthalate (ortho isomer). The reason is that if the structure of the compound to be analyzed is similar to that of the second reference substance, the evaluation can be performed more accurately. Moreover, in the case of phthalates, even for different phthalates, the same reference peak (m / z 149) etc. can be obtained, and the pattern of the mass spectrum of fragment ions is similar. Therefore, even if the compound to be analyzed and the second reference substance are different phthalates, the evaluation can be performed quite accurately. The evaluation method of the mass analysis device in this embodiment obtains information on whether the mass analysis device is in a state suitable for analyzing these compounds to be analyzed.

[0074] (Regarding the mass analyzer)

[0075] Figure 2 It is a conceptual diagram showing the configuration of the mass analyzer of this embodiment. The mass analyzer 1 is a gas chromatograph-mass spectrometer (hereinafter referred to as GC-MS (Gas Chromatograph-Mass Spectrometer)), and includes a measurement unit 100 and an information processing unit 40. The measurement unit 100 includes: a gas chromatograph 10 and a mass analysis unit 30.

[0076] In addition, regarding the mass analyzer of this embodiment, as long as it can ionize and dissociate the esters of phthalic acid and detect the fragment ions obtained by dissociation, there is no particular limitation. For example, it can also be a liquid chromatograph-mass spectrometer (LC-MS (Liquid Chromatography-Mass Spectrometer)).

[0077] The gas chromatograph 10 includes: a carrier gas flow path 11, a sample introduction unit 12 for introducing an analysis target sample, a first standard substance, and a second standard substance (hereinafter referred to as "sample, etc."), a column temperature adjustment unit 13, a separation column 14, and a sample gas introduction tube 15. The mass analysis unit 30 includes: a vacuum container 31, an exhaust port 32, an ionization unit 33 for ionizing the sample, etc. to generate ions In, an ion adjustment unit 34, a mass separation unit 35, and a detection unit 36. The ionization unit 33 includes: an ionization chamber 331, a filament for generating hot electrons 332, and a capture electrode 333.

[0078] The information processing unit 40 includes: an input unit 41, a communication unit 42, a storage unit 43, an output unit 44, and a control unit 50. The control unit 50 includes: a device control unit 51, a data processing unit 52, and an output control unit 53. The data processing unit 52 includes: a mass spectrum generation unit 521, a ratio calculation unit 522, and a determination unit 523. The output control unit 53 includes a notification unit 530.

[0079] The measurement unit 100 separates each component of the sample, etc. by separation analysis and detects the sample, etc.

[0080] The gas chromatograph 10 separates the components contained in the sample, etc. based on physical properties or chemical properties. When it is to be introduced into the separation column 14, the sample, etc. becomes a gas or gas-like state, and it is called a sample gas.

[0081] The carrier gas flow path 11 is a flow path for a carrier gas such as helium, and the carrier gas is introduced into the sample introduction section 12 (arrow A1). The sample introduction section 12 includes a chamber for introducing a sample such as a sample vaporization chamber, temporarily stores a sample injected by an injector such as a syringe or an autosampler (not shown), vaporizes the sample when the sample is a liquid, and introduces the sample gas into the separation column 14 (arrow A2). The method for introducing the sample is not particularly limited, and a splitless introduction method, a split introduction method, or the like can be appropriately used.

[0082] The separation column 14 includes a column such as a capillary column. The temperature of the separation column 14 is controlled to several hundred °C or lower by a column temperature adjustment section 13 including a column oven or the like. Each component of the sample gas is separated based on the distribution coefficient between the mobile phase and the stationary phase of the separation column 14, and each component of the separated sample gas elutes from the separation column 14 at different times, passes through the sample gas introduction tube 15, and is introduced into the ionization chamber 331 of the mass analysis section 30.

[0083] The mass analysis section 30 includes a mass spectrometer, ionizes a sample introduced into the ionization section 33, and performs mass separation and then detection. The path of the ions In generated in the ionization section 33 is schematically shown by an arrow A3.

[0084] In addition, the following example is used for illustration. In the example, a single quadrupole mass analyzer that uses a single quadrupole mass filter for mass separation is used as the mass analysis section 30. However, as long as the mass spectrometer that constitutes the mass analysis section 30 can perform mass analysis and detection on the ions In dissociated by ionization such as electron ionization, the type of the mass spectrometer is not particularly limited. The mass spectrometer may also be a tandem mass spectrometer or a multi-stage mass spectrometer. When the structure does not dissociate a second standard substance or the like during ionization, the second standard substance or the like can also be dissociated by collision-induced dissociation (CID) or the like using a tandem mass spectrometer or a multi-stage mass spectrometer.

[0085] The vacuum container 31 of the mass analysis section 30 includes an exhaust port 32. The exhaust port 32 is connected to a vacuum exhaust system (not shown), and the vacuum exhaust system includes a pump such as a turbomolecular pump that can achieve a high vacuum of 10 -2 Pa or lower and its auxiliary pump. In Table 1, the point of discharging the gas inside the vacuum container 31 is schematically shown by an arrow A4.

[0086] The ionization section 33 of the quality analysis section 30 includes an ion source, which ionizes a sample or the like introduced into the ionization section 33 by electron ionization. The ionization section 33 accelerates the thermoelectrons generated by the filament 332 for generating thermoelectrons with a voltage of several tens of eV or the like applied to the capture electrode 333, and irradiates the sample or the like inside the ionization chamber 331 to generate ions In. During ionization, the sample or the like is dissociated, so the ions In include fragment ions obtained by dissociating the sample or the like. The ions In generated in the ionization section 33 are introduced into the ion adjustment section 34.

[0087] In addition, the method of ionization performed by the ionization section 33 is not particularly limited as long as it involves dissociation. For example, chemical ionization such as positive ion chemical ionization, negative ion chemical ionization, and atmospheric pressure chemical ionization can also be used. Moreover, in the case where dissociation is performed separately after ionization using a mass analyzer with two or more stages, the method of ionization is not particularly limited.

[0088] The ion adjustment section 34 of the quality analysis section 30 includes an ion transport system such as a lens electrode or an ion guide, and adjusts the ions In by converging them through electromagnetic action. The ions In emitted from the ion adjustment section 34 are introduced into the mass separation section 35.

[0089] The mass separation section 35 of the quality analysis section 30 includes a quadrupole mass filter, which performs mass separation on the introduced ions In. The mass separation section 35 selectively allows the ions In to pass through based on the m / z value by applying a voltage to the quadrupole mass filter. The ions In mass-separated in the mass separation section 35 are incident on the detection section 36.

[0090] In addition, the mass analyzer constituting the mass separation section is not particularly limited, and a mass analyzer such as a time-of-flight type can be used.

[0091] The detection section 36 of the quality analysis section 30 includes an ion detector, which detects the incident ions In. The detection section 36 performs A / D conversion on the detection signal obtained by detecting the incident ions In using an analog / digital (A / D) converter (not shown), and outputs the digitized detection signal as measurement data to the control section 50 of the information processing section 40 (arrow A5).

[0092] The information processing section 40 includes an information processing device such as a computer. In addition to serving as an interface with the user, it also performs processing such as communication, storage, and calculation related to various data.

[0093] In addition, the information processing unit 40 may also be configured as a single device integrated with the measurement unit 100. Moreover, a part of the data used by the mass spectrometry device 1 may be stored in a remote server or the like, and a part of the arithmetic processing performed by the mass spectrometry device 1 may be carried out in a remote server or the like.

[0094] The input unit 41 is composed of input devices such as a mouse, a keyboard, various buttons, or a touch screen. The input unit 41 receives information required for the control of the measurement unit 100 or the processing of the control unit 50 from the user. The communication unit 42 is composed of a communication device capable of communicating via a wireless connection or a wired connection such as the Internet, and appropriately transmits and receives data related to the control of the measurement unit 100 or the processing of the control unit 50.

[0095] The storage unit 43 includes a non-volatile storage medium and stores measurement data, a program for the control unit 50 to execute processing, data required for the data processing unit 52 to perform processing, and data obtained through the said processing. The output unit 44 is composed of a display device such as a liquid crystal monitor or a printer. The output unit 44 displays a notification of the content indicating that the mass spectrometry device 1 is not in a state suitable for analysis determined by the evaluation method of the mass spectrometry device of the present embodiment or data obtained through the processing of the data processing unit 52 on the display device, or outputs it by printing using a printer.

[0096] The control unit 50 includes a processor such as a Central Processing Unit (CPU) and controls the operations of the respective parts of the measurement unit 100 or processes the measurement data.

[0097] The device control unit 51 of the control unit 50 controls the operations of the respective parts of the measurement unit 100. For example, the device control unit 51 can detect the ion In by a scanning mode in which the m / z of the ions passing through the mass separation unit 35 is continuously changed. In this case, the device control unit 51 changes the voltage of the mass separation unit 35 so that the ions In having an m / z within a range (for example, 30 to 500, etc.) set based on the input from the input unit 41 or the like selectively pass through the mass separation unit 35. Furthermore, the device control unit 51 controls the voltage values of the respective parts of the mass spectrometry device 1 during calibration such as mass calibration.

[0098] The data processing unit 52 of the control unit 50 processes and analyzes the measurement data. The data processing unit 52 analyzes the mass spectrum of the fragment ions of the second reference substance and obtains information on whether the mass spectrometry device 1 is in a state suitable for analysis. In addition, the data processing unit 52 can perform various analyses such as quantification of the sample to be analyzed.

[0099] The mass spectrometry generation unit 521 makes the m / z of the ions In correspond to the intensity of the detection signal, and creates data corresponding to the mass spectrometry (hereinafter referred to as mass spectrometry data).

[0100] The ratio calculation unit 522 detects a reference peak value and a comparison target peak value from the mass spectrometry of the fragment ions of the second reference substance, and calculates the ratio (intensity ratio) of the intensity detected for the comparison target peak value to the intensity detected for the reference peak value. For example, the ratio calculation unit 522 refers to the data (such as m / z 148 to 150) stored in the storage unit 43 or the like that represents the range for detecting the reference peak value and the comparison target peak value, and uses the peak value with the highest intensity detected within the said range as the reference peak value and the comparison target peak value respectively.

[0101] The determination unit 523 determines whether the mass analyzer is in a state suitable for analysis based on the calculated intensity ratio. The determination unit 523 refers to the numerical value of the said allowable range stored in the storage unit 43 or the like, and determines whether the calculated intensity ratio is included in the allowable range (hereinafter referred to as intensity ratio determination). When there are multiple comparison target peak values, the determination unit 523 performs intensity ratio determination for each comparison target peak value. Even if there is one non - allowable comparison target peak value, it can be considered that the mass analyzer 1 is not in a state suitable for analysis.

[0102] The output control unit 53 generates an output image including the mass spectrometry obtained through the processing of the data processing unit 52 or information indicating the result of the intensity ratio determination, etc., and controls the output unit 44 to output the said output image.

[0103] The notification unit 530 of the output control unit 53 outputs a notification for communicating the said content to the user of the mass analyzer 1 (hereinafter simply referred to as the user) when the mass analyzer 1 is not in a state suitable for analysis. For example, when the mass analyzer 1 is determined to be not in a state suitable for analysis according to the result of the intensity ratio determination by the determination unit 523, the notification unit 530 can cause the output unit 44 to output words such as "There is a possibility that high - precision analysis cannot be performed", "Failure (FAIL)", etc. for warning. Furthermore, the notification unit 530 can also cause it to output information about the comparison target peak value determined to be outside the allowable range of the intensity ratio. This information is, for example, the m / z of the said comparison target peak value, whereby the range of m / z where there is a problem can be conveyed to the user. When it is determined that the mass analyzer 1 is in a state suitable for analysis according to the result of the intensity ratio determination, the notification unit 530 can also cause the output unit 44 to output words such as "Pass".

[0104] (Regarding the analysis method)

[0105] Figure 3This is a flowchart showing the process of the analysis method of this embodiment. In step S1001, the quality analysis unit 30 performs a quality analysis on the first reference material, and the device control unit 51 calibrates the mass analysis device 1. After step S1001 ends, step S1003 starts. In step S1003, the quality analysis unit 30 performs a quality analysis on the phthalic acid ester (second reference material), and detects a plurality of fragment ions generated by the dissociation of the phthalic acid ester. After step S1003 ends, step S1005 starts.

[0106] In step S1005, the ratio calculation unit 522 calculates the ratio of the intensities of the reference peak and the comparison object peak of the fragment ions (intensity ratio). After step S1005 ends, step S1007 starts. In step S1007, the determination unit 523 determines whether the intensity ratio is within a specified range (allowable range). When the intensity ratio is within the allowable range, the determination unit 523 makes an affirmative determination for step S1007 and starts step S1009. When the intensity ratio is not within the allowable range, the determination unit 523 makes a negative determination for step S1007 and starts step S1011.

[0107] In step S1009, the mass analysis device 1 analyzes the analysis target sample. The information obtained in this analysis is output by the output unit 44 and the like. After step S1009 ends, the process ends.

[0108] In step S1011, the notification unit 530 causes the output unit 44 to output a notification indicating that the mass analysis device 1 is not in a state suitable for analysis. After step S1011 ends, step S1013 starts. In step S1013, the user repairs or adjusts the mass analysis device. After step S1013 ends, the process ends.

[0109] In addition, in step S1013, the device control unit 51 may also calibrate the mass analysis device 1 based on an evaluation such as the result of the intensity ratio determination.

[0110] (Regarding the reagent for mass analysis)

[0111] In this embodiment, a reagent for mass analysis is provided for evaluating a mass analysis device based on the intensity ratio of a plurality of fragment ions generated by the dissociation of a phthalic acid ester obtained through mass analysis. This reagent for mass analysis contains the second reference material. Thus, a reference material for correctly evaluating whether a mass analysis device is in a state suitable for analyzing chemicals such as phthalic acid esters can be easily prepared.

[0112] According to the above embodiment, the following effects are obtained.

[0113] (1) The evaluation method of the mass spectrometry apparatus according to the present embodiment includes: performing mass spectrometry on the phthalic acid ester by the mass spectrometry apparatus 1 to detect a plurality of ions In generated by dissociation of the phthalic acid ester; and obtaining information on whether the mass spectrometry apparatus 1 is in a state suitable for analysis based on the intensity ratio of the detected plurality of ions In. Thus, it is possible to correctly evaluate whether the mass spectrometry apparatus 1 is in a state suitable for analyzing chemical substances such as phthalic acid esters. If such an evaluation can be correctly performed, even without preparing calibration curves for each of the compounds to be analyzed, it is possible to analyze using the information in the database by comparing with the analysis conditions in the generalized database. As a result, it is possible to analyze more compounds more quickly. In the present embodiment, the "ratio" is a relationship represented by A:B or A / B between A and B, and includes "rate" (A / B).

[0114] (2) In the evaluation method of the mass spectrometry apparatus according to the present embodiment, the information can be obtained based on a plurality of ratios of the intensities between three or more fragment ions detected. Thus, it is possible to perform a more accurate evaluation using the information on the intensities of three or more fragment ions.

[0115] (3) In the evaluation method of the mass spectrometry apparatus according to the present embodiment, the second reference substance is a phthalic acid ester, and the detected plurality of ions In may include ions corresponding to peaks in the range where the m / z value is 148 or more and 150 or less. In this case, since the peaks commonly detected in the fragment ions of the phthalic acid ester are used for evaluating the mass spectrometry apparatus 1, it is possible to correctly perform the evaluation even when various phthalic acid esters are used as the analysis target.

[0116] (4) In the evaluation method of the mass spectrometry apparatus according to the present embodiment, it is possible to determine whether the mass spectrometry apparatus 1 is in a state suitable for analysis based on whether the ratio of the intensity of the comparison target peak to the intensity of the reference peak in the range where the m / z value is 148 or more and 150 or less is within a specified range. Thus, since the peaks commonly detected in the fragment ions of the phthalic acid ester are used as a reference for evaluating the mass spectrometry apparatus 1, it is possible to perform a more accurate evaluation even when various phthalic acid esters are used as the analysis target.

[0117] (5) In the evaluation method of the mass spectrometry apparatus according to the present embodiment, the phthalic acid ester is dissociated by electron ionization, positive ion chemical ionization, negative ion chemical ionization, atmospheric pressure chemical ionization, or collision-induced dissociation. Thus, it is possible to correctly perform the evaluation using the information on the mass spectra obtained by using these ionization methods in the past.

[0118] (6)In the evaluation method of the mass spectrometry apparatus according to the present embodiment, when the mass spectrometry apparatus 1 is not in a state suitable for analysis, a notification is output. Thereby, information about the mass spectrometry apparatus 1 can be easily conveyed to the user.

[0119] (7)The calibration method of the mass spectrometry apparatus according to the present embodiment can evaluate the mass spectrometry apparatus 1 by the evaluation method of the mass spectrometry apparatus, and calibrate the mass spectrometry apparatus 1 based on this evaluation. Thereby, calibration of the mass spectrometry apparatus 1 can be efficiently performed based on the evaluation of the correct mass spectrometry apparatus 1 using esters of phthalic acid.

[0120] (8)The analysis method according to the present embodiment includes evaluating the mass spectrometry apparatus 1 by the evaluation method of the mass spectrometry apparatus; and performing analysis using the mass spectrometry apparatus 1. Thereby, the accuracy of the analysis obtained using the mass spectrometry apparatus 1 can be correctly grasped.

[0121] (9)The mass spectrometry apparatus according to the present embodiment includes: a mass analysis unit 30 that performs mass analysis on esters of phthalic acid and detects a plurality of ions In generated by dissociation of the esters of phthalic acid; and an information acquisition unit (data processing unit 52) that acquires information on whether the mass analysis unit 30 is in a state suitable for analysis based on the intensity ratio of the plurality of detected ions In. Thereby, a correct evaluation can be made as to whether the mass spectrometry apparatus 1 is in a state suitable for analysis of chemical substances such as esters of phthalic acid.

[0122] The following modifications are also within the scope of the present invention and can be combined with the above-described embodiment. In the following modification examples, parts having the same structure and function as those in the above-described embodiment are referred to by the same reference numerals, and description thereof is appropriately omitted.

[0123] (Modification Example 1)

[0124] In the above-described embodiment, when analyzing an analysis target sample, the value obtained in the analysis may also be corrected using the intensity ratio calculated for the second standard substance. For example, let the intensity ratio for the first peak be 15% within the allowable range (5% or more and 15% or less). In order to approach the midpoint 10% of the allowable range, it is only necessary to make the value near m / z 279 corresponding to the first peak approach two-thirds. Therefore, even for the analysis of an analysis target sample, by performing such correction, more correct data can be prepared.

[0125] (Modification Example 2)

[0126] Esters of phthalic acid are also used in building materials and are therefore also present in indoor air or the atmosphere. Therefore, indoor air or the atmosphere can also be trapped as a second reference material. Thus, the second reference material can be collected near the mass analyzer 1 or the like.

[0127] (Modification 3)

[0128] In the above-described embodiment, the first reference material and the second reference material are introduced into the gas chromatograph 10, and they can also be directly introduced into the ionization section 33 of the mass analysis section 30.

[0129] The present invention is not limited to the content of the above-described embodiment. Other aspects considered within the technical idea of the present invention are also included in the scope of the present invention.

Claims

1. An evaluation method for a mass analysis device, comprising: performing mass calibration of the mass analysis device using a reference substance; after the mass calibration, performing mass analysis on the ester of phthalic acid using the mass analysis device to detect a plurality of fragment ions generated by dissociation of the ester of phthalic acid, and generating a mass spectrum showing peaks corresponding to the plurality of fragment ions, wherein the mass spectrum includes a reference peak and a comparison target peak, and the comparison target peak is one or more peaks having a higher detected intensity among the peaks obtained by removing the reference peak in the mass spectrum representing the fragment ions; and based on whether the intensity ratio of the comparison target peak relative to the intensity of the peak corresponding to the plurality of detected fragment ions that becomes the reference peak is within an allowable range, obtaining information on whether the mass analysis device is in a state suitable for analysis, wherein if the intensity ratio is within the allowable range, the information is that the mass analysis device is in a state suitable for analysis, if the intensity ratio is outside the allowable range, the information is that the mass analysis device is not in a state suitable for analysis.

2. The evaluation method for a mass analysis device according to claim 1, wherein the information is obtained based on a plurality of the intensity ratios among 3 or more of the detected fragment ions.

3. The evaluation method for a mass analysis device according to claim 1, wherein the ester of phthalic acid is an ester of the ortho-isomer of phthalic acid.

4. The evaluation method for a mass analysis device according to claim 3, wherein the ester of phthalic acid is selected from the group consisting of diisobutyl phthalate, dibutyl phthalate, butyl benzyl phthalate, bis(2-ethylhexyl) phthalate, di-n-octyl phthalate, diisononyl phthalate, diisodecyl phthalate, mono(2-ethylhexyl) phthalate, dimethyl phthalate, diethyl phthalate, dipropyl phthalate, bis(2-methoxyethyl) phthalate, bis(2-butoxyethyl) phthalate, n-pentyl isopentyl phthalate, dipropylheptyl phthalate, di-n-pentyl phthalate, diisopentyl phthalate, di-n-hexyl phthalate, diisohexyl phthalate, dicyclohexyl phthalate, dibenzyl phthalate, diheptyl phthalate, diisoheptyl phthalate, dinonyl phthalate, didecyl phthalate, di-undecyl phthalate, diisoundecyl phthalate, and diisotridecyl phthalate.

5. The evaluation method for a mass analysis device according to claim 4, wherein the ester of phthalic acid is bis(2-ethylhexyl) phthalate.

6. The evaluation method for a mass analysis device according to claim 5, wherein the plurality of detected fragment ions include fragment ions corresponding to the reference peak having an m / z value in the range of 148 or more and 150 or less.

7. The evaluation method for a mass analysis device according to claim 6, wherein Based on whether the intensity ratio of the peak of the comparison object relative to the reference peak whose m / z value is in the range of 148 or more and 150 or less among the peaks corresponding to the detected multiple fragment ions is within the allowable range, it is determined whether the mass analyzer is in a state suitable for the analysis.

8. The evaluation method of the mass analyzer according to claim 7, wherein the ester of phthalic acid is bis(2-ethylhexyl) phthalate, the comparison object peak is at least one of a first peak whose m / z value is in the range of 278 or more and 280 or less, a second peak whose m / z value is in the range of 166 or more and 168 or less, a third peak whose m / z value is in the range of 112 or more and 114 or less, a fourth peak whose m / z value is in the range of 70 or more and 72 or less, and a fifth peak whose m / z value is in the range of 56 or more and 58 or less; the allowable range in the case of the first peak is 5% or more and 15% or less, the allowable range in the case of the second peak is 33% or more and 48% or less, the allowable range in the case of the third peak is 8% or more and 16% or less, the allowable range in the case of the fourth peak is 17% or more and 30% or less, and the allowable range in the case of the fifth peak is 17% or more and 44% or less.

9. The evaluation method of the mass analyzer according to any one of claims 1 to 8, wherein the ester of phthalic acid is dissociated by electron ionization, positive ion chemical ionization, negative ion chemical ionization or collision-induced dissociation.

10. The evaluation method of the mass analyzer according to any one of claims 1 to 8, which comprises: outputting a notification when the mass analyzer is not in a state suitable for the analysis.

11. A calibration method of a mass analyzer, comprising: evaluating the mass analyzer by the evaluation method of the mass analyzer according to any one of claims 1 to 8; and calibrating the mass analyzer based on the evaluation.

12. An analysis method, comprising: evaluating the mass analyzer by the evaluation method of the mass analyzer according to any one of claims 1 to 8; and performing an analysis using the mass analyzer.

13. The analysis method according to claim 12, wherein data obtained by the analysis is calibrated based on the intensity ratio of the comparison object peak relative to the intensity of the reference peak among the peaks corresponding to the detected multiple fragment ions.

14. A mass analyzer, comprising: a mass analysis unit that performs mass analysis on the ester of phthalic acid to detect multiple fragment ions generated by dissociation of the ester of phthalic acid and generates a mass spectrum showing peaks corresponding to the multiple fragment ions, wherein the mass spectrum includes a reference peak and a comparison object peak, and the comparison object peak is one or more peaks with higher detected intensity among the peaks obtained by selecting and removing the reference peak in the mass spectrum representing the fragment ions; and An information acquisition unit acquires information on whether the mass analysis unit is in a state suitable for analysis based on whether the intensity ratio of the peak of the comparison target relative to the intensity of the peak corresponding to the plurality of detected fragment ions that becomes the reference peak is within an allowable range, where if the intensity ratio is within the allowable range, the information is that the mass analysis device is in a state suitable for analysis, if the intensity ratio is outside the allowable range, the information is that the mass analysis device is not in a state suitable for analysis.

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