JP6631131B2 - Ion conversion method and ion conversion device for ionic compound - Google Patents

Description

  The present invention relates to an ion conversion method and an ion conversion device for an ionic compound.

  Ion chromatography is employed in various official methods as a method for analyzing ionic components, and in many cases, is widely used as an analyzer based on an electrical conductivity detection method using a suppressor method.

  The analyzer includes a separation step by chromatography using an eluent containing an electrolyte and a separation medium, a suppression step of suppressing the electric conductivity derived from the electrolyte of the eluent, and an electric conductivity detector for separating and eluted ionic components. And a detection step of detecting the above.

  As a countermeasure for the analysis of weakly acidic ions such as organic acids, the solution eluted from the suppressor is introduced into the first electric conduction detector to detect the strongly acidic ions, and then the alkali metal ions are discharged from the effluent containing the weakly acidic ions. To a salt converter containing a cation exchange resin having a cation as a counter ion, convert the counter ion from a hydrogen ion to an alkali metal ion, and then introduce the counter ion into a second electric conductivity detector, where the weakly acidic ion component is Methods for detecting the sensitivity are disclosed (Patent Documents 1 and 2).

  In the electric conductivity detection method by the suppressor method, conversion of a counter ion is usually performed in the suppression step. For example, in anion analysis, sodium hydroxide used as the electrolyte of the eluent is converted to water, sodium carbonate and sodium hydrogen carbonate are converted to carbonic acid, and the ionic compound AX to be measured is converted to HX. As a result, the conductivity of the eluent decreases, and the conductivity of the ionic compound HX generated after the conversion increases, so that highly sensitive detection of ion components can be achieved by changes in both the noise level and the signal intensity. Becomes possible. However, since the dissociation state of the ionic compound HX varies depending on the concentration based on its dissociation characteristics (pKa), it is known that the calibration curve is bent depending on the ion species, which affects the quantitative accuracy. In particular, this tendency appears remarkably in weakly acidic and weakly basic ion components, and at the same time, there is a problem that the detection sensitivity is lowered (Non-Patent Document 1).

  As a detection method other than the suppressor method-electric conductivity detection method, an absorbance detection method, an electrochemical detection method, a fluorescence detection method, and the like are also used. Since these detection methods are hardly affected by the dissociation state due to the concentration change, they have excellent linearity of the calibration curve and high quantification accuracy. However, this is a method for selectively detecting a specific ion species that matches the detection principle, and there is a problem in general use.

  On the other hand, Mori et al. Disclose a method of performing absorbance detection after a salt conversion treatment on ions to be analyzed (Patent Documents 3 and 4). In this method, after ion components are separated by ion exclusion chromatography using water as an eluent, the effluent from the column is introduced into an ion-exchange resin on which ions having UV absorption are immobilized, and the ion to be analyzed or its counter ion After converting into a salt having UV absorption, absorbance detection is performed. This method has the advantage that the absorbance detection method can be widely applied to separable ionic compounds, but since the eluent is limited to water, it is limited to application to chromatography using a column that can be separated only with water. However, there is a problem in application to ion exchange chromatography used for general ion analysis.

  In recent years, mass spectrometry-based detection methods have been widely used in HPLC as highly sensitive detection methods with constant performance. In the detection of ions, there has been a problem that, due to the limitation of applicable molecular weight, it is not suitable for detecting low molecular weight ions such as sodium ions and chloride ions.

Japanese Patent Publication No. 7-505960 Japanese Patent No. 4122228 Japanese Patent No. 3924618 Japanese Patent No. 3924622

Okada et al., Separation and analysis of ionic chemical species by chromatography, 2002, pp. 15-26. 69-104, 135-151

  The present invention has been made in view of the problems of the prior art, and its object is to convert an ionic component constituting an ionic compound, and finally to a method for converting to an ionic species that can be detected by a mass detector and its method. An object of the present invention is to provide an analyzer.

As a result of intensive studies to achieve the above object, the present invention has been completed.
That is, the present invention includes the following [1] to [4].
[1]
A method of converting ions,
The ionic compound AB (where one of A and B is a cation and the other is an anion) is converted by a salt converter to obtain AD (where D is an ion that can be detected by a mass detector). Ion conversion method.
[2]
The method for exchanging ions according to [1], wherein prior to the method according to [1], (1) the ionic compound AB is converted with an ion exchange medium to obtain CB (where C is H + ion or OH- ion).
(2) The method according to [1], comprising a step of converting the CB obtained in the step (1) with a salt converter to obtain an AB.
[3]
The method according to [1] or [2], wherein the ion exchange medium and / or the salt converter is an ion exchange column or an ion exchange membrane.
[4]
An apparatus for detecting ions with a detector,
Means for converting an ionic compound AB (wherein one of A and B is a cation and the other is an anion) to AD (where D is an ion that can be detected by a mass detector), and a mass detector. Ion detector.
[5]
An apparatus for detecting ions of the ionic compound AB, wherein before the ion detection according to [4],
(1) An ion-exchange medium which converts ionic compound AB to CB (wherein C represents H + ion or OH- ion), and (2) converts CB obtained in step (1). AB salt converter,
The apparatus according to [4], comprising:
[6]
The ion detector according to [4] or [5], wherein the ion exchange medium and / or the salt converter is an ion exchange column or an ion exchange membrane.

  In the present invention, the ionic compound AB is not particularly limited, but examples thereof include sodium chloride, potassium nitrate, sodium sulfate, potassium dihydrogen phosphate and the like.

  The ion exchange medium used in the present invention is used in the step of primary conversion of the ionic compound AB into CB. Specifically, in the anion analysis, a strong base cation exchange column, a weakly basic anion exchange column, and in the cation analysis, a strongly acidic cation exchange column and a weakly acidic cation exchange column can be exemplified. . Other examples include an amphoteric ion exchange column having both an anion exchange group and a cation exchange group, a separation column for reversed phase chromatography, a separation column for hydrophilic interaction chromatography, and the like.

  The primary conversion is defined in the present invention in order to distinguish a step of further changing ions by a salt converter described later. Also, this does not preclude having another conversion step before the primary conversion by a known method.

  The salt converter used in the present invention is used to convert the ion compound AB into AD, on which the ions D whose mass can be detected are immobilized. Here, as the ion D whose mass can be detected, an ion paired with the ion A such as a bromate ion can be exemplified, but is not limited thereto. In the present invention, the salt converter is also used for converting CB to AB, and in this case, can be used after the primary conversion.

  The ion D converted from AB to AD by the method of the present invention is guided to a mass detector, and the ion D can be detected by setting m / z according to the molecular weight of the ion D. That is, the quantitative value of the ion B is indirectly calculated from the peak area or the peak height of the ion D detected by the mass detector, and the analysis result of the concentration can be obtained.

  Hereinafter, an example in which the present invention is applied to an ion chromatography system will be described with reference to FIG.

  For the analysis, each ion component in the sample injected from the autosampler 3 is introduced into the separation medium 5 together with the eluent 1, and each ion component is separated by the ion chromatography principle.

  In the present invention, the eluent 1 passes an eluent containing an electrolyte through the separation medium 5, and each ionic component to be analyzed introduced into the separation medium 5 is caused by a difference in interaction with the separation medium 5. Therefore, a difference occurs in the moving speed in the separation medium 5. As a result, the respective ionic components are separated by the separation medium 5, and out of the ionic components, flow out of the separation medium outlet in ascending order of moving speed. At this time, the effluent flowing out of the separation medium 5 contains the electrolyte derived from the eluent 1 and the ions A and B.

  Specific examples of the separation medium used here include a strong base cation exchange column and a weak base anion exchange column in anion analysis, and a strongly acidic cation exchange column and weak acidic cation exchange column in cation analysis. A cation exchange column can be exemplified. Other examples include an amphoteric ion exchange column having both an anion exchange group and a cation exchange group, a separation column for reversed phase chromatography, a separation column for hydrophilic interaction chromatography, and the like.

  The ion exchange medium 6 is used in the step of primary conversion of the ionic compound AB into CB. At that time, the electrolyte derived from the eluent present in the liquid flowing out of the ion exchange medium 6 in the ion exchange medium 6 can be prevented from hindering the mass detection. Specifically, the dissociation degree of the eluent is extremely small, and the eluent is converted into water, which is the same substance as the eluent.

The term “electrolyte” in the “eluent containing an electrolyte” means an electrolyte that can be converted to water. For example, when sodium hydroxide is used as the electrolyte of the eluent, hydrogen ions of the cation exchange resin are ⁺ Means ion exchange between Na ⁺ and H ⁺ + OH ⁻ = H ₂ O to convert to water. When HCl is used as the electrolyte of the eluent, it means that OH ⁻ and Cl ⁻ are ion-exchanged by the hydroxide ions of the anion exchange resin and converted into water with H ⁺ + OH ⁻ = H ₂ O. .

  The salt converter 7 is used to convert the ion B into an ion species whose mass can be detected. In the salt converter 7, the ion species whose mass can be detected is fixed, and the ion B can be changed to the ion species whose mass can be detected after the step of primary conversion of the ion A by the ion exchange medium. The ionic species that have flowed out are guided to the mass detector 8 and detected by setting m / z suitable for the molecular weight of the ionic species. From the peak height or peak area of the detected ion species, a quantitative value of the ion species is calculated as ion B, and an analysis result of the concentration of the ion component can be obtained. Further, the salt converter can be used for converting the ion C into the ion A before converting the ion B into the ion species. In the most preferred embodiment of the present invention, the ionic compound AB (where A and B are cations and the other is an anion) is directly converted by a salt converter to obtain AD (where D is a mass detector). This is an ion conversion method characterized by obtaining detectable ions). In this case, there is an advantage that the apparatus configuration is simplified and the analysis time is shortened. In the present invention, conversion directly by a salt converter means that in the case of analysis of the ionic compound AB, AD is obtained only once by ion conversion of the ionic compound AB using a salt converter.

  Further, the analyzer employing the present invention can be applied to a method for simultaneously analyzing a plurality of different ions to be analyzed in a sample solution to be used. As will be described later in detail in Examples, for example, due to a difference in interaction between each ion component in the sample and the separation medium 5, a difference in the moving speed of each ion component in the sample in the separation medium 5 is caused. Is caused. Next, Na and H can be simultaneously primary-converted simultaneously with a difference in the moving speed for each ion component in the sample, and the ion B can be converted into a detectable ion D by the salt converter. As a result, each ion component can be detected by the detector while each ion component is separated by the difference in the moving speed.

  There is no limitation on the use of any number of primary and / or salt converters in the present invention. For example, when NaCl is used as an ionic compound, it is converted into hydrochloric acid by primary conversion, then converted into sodium chloride, potassium chloride, and potassium nitrate by employing three types of salt converters, and the nitric acid is detected by a detector such as a mass detector. Can be detected by a detector by converting the ion species into a detectable ion species.

It was suggested that mass detection of each anion was possible by direct detection.
Specifically, it has become possible to detect low molecular weight ions such as sodium ions and chloride ions, and to simultaneously analyze a plurality of different ions to be analyzed in a sample solution.

  In the conventionally used ion chromatography method based on the suppressor method-electric conductivity detection, there are cases where the detection sensitivity and the quantitative accuracy are problematic due to the dissociation characteristics of the ionic components. For example, since all the same ion species are detected by their m / z, the detection sensitivity is improved, and an effect of obtaining a highly accurate quantitative analysis result can be expected.

  Since ion separation and detection can be performed by ion chromatography using an electrolyte that can be converted to water, the present invention can be applied to the analysis of ions using various types of separation columns such as an ion exchange column. In addition, by controlling the separation by freely adjusting the electrolyte concentration, the present invention can be applied to ion analysis of a wide range of actual samples such as environmental samples, chemicals, foods, and pharmaceuticals.

1 is a schematic flowchart of an apparatus for implementing the present invention. FIG. 3 is a view showing an MS chromatogram obtained in Example 1. FIG. 4 is a view showing an MS chromatogram obtained in Comparative Example 1. FIG. 9 is a view showing an MS chromatogram obtained in Comparative Example 2. FIG. 9 is a view showing a chromatogram for MS direct detection obtained in Comparative Example 2.

FIG. 1 shows a simplified apparatus configuration for implementing an embodiment of the present invention.
In FIG. 1, 1 indicates an eluent. As the electrolyte used for the eluent, an electrolyte which can be converted into water by passing through the ion exchange medium 6 is used.

  In the case of anion analysis, it is possible to use an alkali aqueous solution having a hydroxide ion as a counter ion, and specifically, sodium hydroxide, potassium hydroxide, ammonium hydroxide, lithium hydroxide, and hydroxide. An electrolyte such as tetraalkylammonium can be exemplified. In the cation analysis, it is possible to use an acid aqueous solution having a hydrogen ion convertible into water as a counter ion. Specifically, hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfone An electrolyte such as an acid can be exemplified. The concentration of the electrolyte in the eluent 1 is preferably 0.01 mmol / L or more and 500 mmol / L or less, and more preferably 0.1 mmol / L or more and 200 mmol / L or less. The eluent 1 may be of a single composition or a mixture of two or more compositions having different concentrations in a stepwise or continuous manner. Further, the eluent 1 may contain a water-soluble organic solvent, and specific examples thereof include alcohols such as methanol, ethanol, and propanol, and acetonitrile.

  The eluent 1 is sent by a liquid sending pump 2, and is introduced into a separation medium 5 in a column oven 4 via an autosampler 3. As the separation medium 5, a separation column for chromatography using an electrolyte can be used. Specifically, for anion analysis, a strongly basic anion exchange column and a weakly basic anion exchange column, and for cation analysis, a strongly acidic cation exchange column and a weakly acidic cation exchange column may be exemplified. Other examples include an amphoteric ion exchange column having both an anion exchange group and a cation exchange group, a separation column for reverse phase chromatography, a separation column for hydrophilic interaction chromatography, and the like. For analysis, a sample injected from the autosampler 3 is introduced into the separation medium 5 together with the eluent 1. The introduced ionic components are separated based on the principle of ion chromatography.

  The ion exchange medium 6 is used so that even if the ionic components derived from the eluent pass through the salt converter, they do not affect the detection by the detector. Therefore, this does not apply when an eluent that does not affect the detection of H2O or the like is used.

  Further, a column type packed with an ion exchange resin or a membrane type using an ion exchange membrane can be used. Specifically, in anion analysis, a column filled with a cation exchange resin of the hydrogen ion type, which can convert cations contained in the eluent into hydrogen ions, or a hydrogen ion is supplied to remove the cations. And a membrane-type suppressor having a cation exchange membrane capable of performing the following. In cation analysis, supply a column or hydroxide ion packed with a hydroxide ion type anion exchange resin that can convert anions contained in the eluent to hydroxide ions, and remove anions A membrane-type suppressor having a cation exchange membrane capable of being used can be exemplified.

  Next, the salt converter 7 for performing the salt conversion is an ion detector capable of detecting, with a detector such as a mass detector, an ion component having a difference in the moving speed for each ion component in the sample in the separation medium 5. By converting to a species, it can be detected by a detector. Further, as a material used for the salt converter, a column or an ion exchange membrane filled with an ion exchange resin can be used. Specifically, in the case of an ion exchange resin, an ion species detectable by a mass detector is used as a counter ion, and iodide type anion exchange resin, bromate ion type anion exchange resin, iodate type Anion exchange resin, sulfonate ion type anion exchange resin having aliphatic and / or aromatic functional groups, metal-metal ligand complex ion type anion exchange resin, alkyl ammonium ion type cation exchange resin, pyridinium Examples thereof include an ion-type cation exchange resin, a sulfonium ion-type cation exchange resin, and a metal-metal ligand complex ion-type cation exchange resin.

  As a method of use, when it is difficult to convert ion components flowing out of the ion exchange medium 6 into ion species capable of mass detection by a direct ion exchange reaction in the salt converter, a preliminary salt is added before the salt converter. A converter can be connected and used. As a preliminary salt converter, a column or an ion exchange membrane packed with an ion exchange resin containing an ion exchange medium can be used, and a plurality of salt converters are used within a range not departing from the gist of the present invention. It is also possible.

  In a preferred embodiment of the present invention, the ionic compound AB (where A and B are cations and the other is an anion) is converted to CB by an ion exchange medium so that the electrolyte derived from the eluent does not hinder mass detection. And then obtaining an AD that is detectable by a mass detector by a salt converter. In a most preferred embodiment of the present invention, an ionic compound AB (where one of A and B is a cation and the other is an anion) is directly converted by a salt converter and AD (where D is detected by a mass detector). (Possible ions). In the present invention, conversion directly by a salt converter means that in the case of analysis of the ionic compound AB, AD is obtained only once by ion conversion of the ionic compound AB using a salt converter.

  It is also possible to employ a salt converter having both the function of the ion exchange medium 6 for converting the ionic components in the eluent and the function of converting the ionic components into ionic species detectable by a detector such as a mass detector. It is possible.

  As the mass detector 8, one whose m / z can be set in the range of 50 to 1000 can be used.

  The mass detector 8 is provided with a data processor 9, which processes the m / z intensity data detected by the mass detector 8 and outputs the processed data as a chromatogram.

  Hereinafter, examples will be described in order to explain the present invention in more detail, but the present invention is not limited to these examples. In the embodiment, an analysis example using a salt conversion process will be described.

Example 1
According to the schematic diagram of FIG. 1, analysis was performed by mass detection.
As measurement conditions for performing anion analysis, 2 mmol / L sodium hydroxide was used as one eluent, and the solution was sent at a flow rate of 0.2 mL / min. The liquid sending pump 2 is a DP-8020 type pump (manufactured by Tosoh Corporation), the autosampler 3 is an AS-8020 autosampler (manufactured by Tosoh Corporation), and the column oven is a CO 2 A -8020C type column oven (manufactured by Tosoh Corporation) was used.
Using a TSKgel SuperIC-AZ (inner diameter 4.6 mm, length 1 cm) for the separation column 5 and using a strongly acidic ion exchange resin (TSKgel Suppres IC-A, Tosoh) using hydrogen ions as counter ions as the ion exchange medium 6 (Manufactured by K.K.) was packed in a column having an inner diameter of 4.6 mm and a length of 5 cm. The salt converter of No. 7 has a counter ion of a strongly acidic ion exchange resin (TSKgel Suppress IC-A, manufactured by Tosoh Corporation) as a sodium ion and is packed in a column having an inner diameter of 4.6 mm and a length of 1 cm. A salt packed in a column having an inner diameter of 4.6 mm and a length of 1 cm using bromate as a counter ion of a strongly basic exchange resin (TSKgel Suppress IC-C, manufactured by Tosoh Corporation) using hydroxide ion as a counter ion. Two salt converters of the converter were used connected in series.

  A high-performance liquid chromatograph mass spectrometer LCMS-8030 (manufactured by Shimadzu Corporation) is used for the mass detector of No. 8, and a dedicated workstation LabSolution LCMS is used as the data processor of No. 9, and instrument control and chromatograms are used. Data collection and analysis were conducted.

  The measurement temperature was 25 ° C., and mass detection was performed in negative mode of ESI at an interface voltage of −3.5 kV, a DL temperature of 250 ° C., and a heat block temperature of 400 ° C., and the precursor ion m / z was 127.00. , The product ion m / z was set to 111.05, and detection was performed in the MRM mode. FIG. 2 shows an MS chromatogram obtained by injecting 20 μL of a mixed solution of sodium chloride and sodium nitrate as a sample (concentrations are 10 mg / L as chloride ions and nitrate ions, respectively) from an autosampler.

  Peaks derived from chloride ions and nitrate ions were observed in the mass detector, and immediately after elution from the ion exchange medium, each ion was present as hydrochloric acid and nitric acid, and each ion was converted to sodium bromate by a salt converter. This shows that bromate ions derived from each of the separated anions were detected by the mass detector.

Comparative Example 1
Using the system of FIG. 1, a counter ion of a strongly acidic ion exchange resin (TSKgel Suppress IC-A, manufactured by Tosoh Corporation) was used as a sodium ion counter as a salt converter, and the column was packed into a column having an inner diameter of 4.6 mm and a length of 1 cm. Only those used were used. Note that there is only one type of salt converter.

  In mass detection, in the negative mode of ESI, ionization is performed at an interface voltage of -3.5 kV, a DL temperature of 250 ° C, and a heat block temperature of 400 ° C, the precursor ion m / z is 127.00, and the product ion m / z. Was set to 111.05, and detection was performed in the MRM mode. As a sample, 20 μL of a mixed solution of sodium chloride and sodium nitrate (concentrations were 10 mg / L as chloride ion and nitrate ion, respectively) was injected from an autosampler.

Other than that, the anion was analyzed in the same manner as in Example 1, and the obtained MS chromatogram is shown in FIG.
As a result, peaks derived from chloride ions and nitrate ions were not observed, and conversion to bromate ions was not performed, so that they could not be detected by the mass detector.

Comparative Example 2
Using the system of FIG. 1, a counter ion of a strongly acidic ion exchange resin (TSKgel Suppress IC-A, manufactured by Tosoh Corporation) was used as an ion exchange medium, and a counter ion of sodium was packed in a column having an inner diameter of 4.6 mm and a length of 1 cm. Only those used were used. No salt converter was used.

  In mass detection, ionization was performed in negative mode of ESI at an interface voltage of -3.5 kV, a DL temperature of 250 ° C, and a heat block temperature of 400 ° C, and the m / z of the precursor ion was 35.50 for direct detection of chloride ion. 45, the m / z of the product ion was set to 35.45, the m / z of the precursor ion was set to 62.00, and the m / z of the product ion was set to 46.15 for direct detection of nitrate ion, and the MRM mode was set. Was detected. As a sample, 20 μL of a mixed solution of sodium chloride and sodium nitrate (concentrations were 10 mg / L as chloride ion and nitrate ion, respectively) was injected from an autosampler.

  Otherwise, the anion was analyzed in the same manner as in Example 1, and the obtained MS chromatograms are shown in FIG. 4 and FIG. As a result, in FIG. 5, the peak of the chloride ion itself was directly detected by mass detection without converting the chloride ion into another ion component. As compared with Example 1, a chromatogram having large noise and low detection sensitivity was obtained.

  In FIG. 4, the peak of the nitrate ion itself was directly detected by mass detection without converting the nitrate ion into another ion component. However, since chloride ions have a smaller mass number than nitrate ions and the like, direct detection with a mass detector resulted in lower detection sensitivity than the result of Example 1. In other words, it has been shown that, when it is desired to detect ions having a small mass number such as chloride ions, sufficient sensitivity can be obtained in mass spectrometry by converting to ions having a larger mass number.

DESCRIPTION OF SYMBOLS 1 Eluent 2 Liquid sending pump 3 Autosampler 4 Column oven 5 Separation medium 6 Ion exchange medium 7 Salt converter 8 Mass detector 9 Data processor 10 Peak derived from chloride ion 11 Peak derived from nitrate ion

Claims (6)

A method of converting ions,
An ionic compound AB (where A is a cation and B is an anion) is converted by a salt converter into AD (where D is a metal-metal ligand complex ion and is an anion, iodide ion, Any one of a bromate ion, an iodate ion, and a sulfonate ion having an aliphatic and / or aromatic functional group). The method for exchanging ions according to claim 1, wherein before the method according to claim 1, (1) the ionic compound AB is converted by an ion exchange medium to obtain CB (where C is H + ion To represent)
2. The method according to claim 1, further comprising the step of: (2) converting the CB obtained in step (1) with a salt converter to obtain AB. 3. The method according to claim 2 , wherein the ion exchange medium and / or the salt converter is an ion exchange column or an ion exchange membrane. An apparatus for detecting ions with a detector, wherein an ionic compound AB (where A is a cation and B is an anion) is converted to AD (where D is a metal-metal ligand complex ion and an anion) Any of iodide ions, bromate ions, iodate ions, and sulfonate ions having an aliphatic and / or aromatic functional group) and a mass detector. apparatus. It is a device for detecting the ions of the ionic compound AB, before the ion detection according to claim 4,
(1) An ion exchange medium that converts ionic compound AB into CB (where C represents H + ion), and (2) a salt that converts CB obtained in step (1) into AB converter,
5. The device according to claim 4, comprising: The ion detector according to claim 5 , wherein the ion exchange medium and / or the salt converter is an ion exchange column or an ion exchange membrane.

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