Organic compounds, reagents, and analytical methods

Abstract

To provide an organic compound for simple, rapid and accurate measurement of a trace amount of a chemical substance (substance to be tested), and to provide a reagent that contains the organic compound, and an analysis method in which the organic compound or the reagent is used.SOLUTION: The organic compound of the present invention is represented by the following chemical formula (1). (In the formula, X is a thiol group or an amino group, R1, R2, R3, R4, and R5 are each independently a hydrocarbon group, A is a functional group containing a single bond between a heteroatom and a carbon atom, and Y- is an anion.)SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an organic compound for measuring trace amounts of chemical substances, a reagent containing the organic compound, and an analytical method using the organic compound or the reagent. [Background technology]

[0002] It is important that products that come into contact with humans, such as pharmaceuticals and cosmetics, do not cause allergic reactions under actual conditions of use. Therefore, during product development, it is necessary to evaluate the risk of skin sensitization of the ingredients used. Skin sensitization has been evaluated using animal tests such as the Guinea Pig Maximization Test, the Buehler Test, and the Local Lymph Node Assay.

[0003] In recent years, alternative tests have been developed to evaluate the skin sensitization potential of chemicals in vitro without using animals, and skin sensitization tests using cysteine ​​peptides, lysine peptides (Non-Patent Document 1) and amino acid derivatives have been proposed (Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-37995 [Patent Document 2] Japanese Patent Application Laid-Open No. 2011-59102 [Non-patent literature]

[0005] [Non-Patent Document 1] GFGerberick et al., Quantification of Chemical Peptide Reaction for Screening Contact Allergens: A Classification Tree Model Approach, Toxicol. Sci., 97(2), 417-427:2007. Summary of the Invention [Problem to be solved by the invention]

[0006] From the perspective of animal welfare, animal testing should be avoided, and it is necessary to realize alternative methods for evaluating skin sensitization that do not use animals. While the alternative methods described above are good methods for measuring the skin sensitization potential of the main components contained in test substances in a simple and rapid manner, there are concerns that they may not accurately evaluate the risk of skin sensitization caused by trace impurities. Skin sensitization tests using cysteine ​​peptides, lysine peptides (Non-Patent Document 1) and amino acid derivatives (Patent Documents 1 and 2) have been found to have problems with the detection sensitivity of the resulting trace amounts of bound substances, even when highly sensitive mass spectrometry is used.

[0007] An object of the present invention is to provide an organic compound for easily, quickly, and accurately measuring trace amounts of chemical substances (test substances), a reagent containing the organic compound, and an analytical method using the organic compound or the reagent. [Means for solving the problem]

[0008] As a result of intensive research to solve the above problems, the present inventors discovered that trace amounts of chemical substances can be analyzed simply, selectively, and with high sensitivity by labeling chemical substances such as skin sensitizers with a labeling reagent having a specific structure and then subjecting the labeled chemical substances to analysis, thereby completing the present invention.

[0009] That is, the present invention relates to an organic compound represented by the following chemical formula (1). [ka] (wherein X is a thiol group or an amino group, and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently a hydrocarbon group, A is a functional group containing a single bond between a heteroatom and a carbon atom, and Y - is an anion.)

[0010] The present invention also relates to a reagent containing the organic compound.

[0011] Furthermore, the present invention relates to an analytical method in which the organic compound is reacted with a chemical substance to obtain a reaction product, and then the reaction product is separated and detected. [Effects of the Invention]

[0012] The organic compound of the present invention has a functional group (thiol group or amino group) that is highly reactive to trace amounts of chemical substances (such as skin sensitizers), a functional group (quaternary ammonium group) that enables highly sensitive detection of the reactant, and a functional group (functional group containing a single bond between a heteroatom and a carbon atom) that enables highly selective detection of the reactant, so that trace amounts of chemical substances can be measured simply, quickly, and accurately using a general-purpose analytical method and analytical device. The organic compound, reagent, and analytical method of the present invention can be used, for example, to evaluate the skin sensitization of trace amounts of chemical substances and to quantitatively measure trace amounts of chemical substances. [Brief explanation of the drawings]

[0013] [Figure 1] Chromatograms of the reaction products of TMAS, Cys-P, or NAC with the test substance. DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention will be described in detail below.

[0015] <Organic compounds> The organic compound of the present invention is represented by the following chemical formula (1). [ka] (wherein X is a thiol group or an amino group, and R 1 , R 2 , R 3 , R 4 , and R 5 are each independently a hydrocarbon group, A is a functional group containing a single bond between a heteroatom and a carbon atom, and Y - is an anion.)

[0016] X is a thiol group or an amino group, which is a functional group that is reactive to chemical substances such as skin sensitizers (eg, α,β-unsaturated ketones, acid anhydrides, and aldehydes).

[0017] R 1 , R 2 , R 3 , R 4 , and R 5 are each independently a hydrocarbon group, and examples of the hydrocarbon group include a linear or branched aliphatic saturated or unsaturated hydrocarbon group, an alicyclic saturated or unsaturated hydrocarbon group (including a bridged ring or a fused ring), an aromatic hydrocarbon group, and an organic group in which two or more of these are bonded together. The hydrocarbon group may also have various substituents as long as they do not impede the effects of the present invention.

[0018] R 1 From the viewpoint of facilitating detection by an analytical device, is preferably a hydrocarbon group having no substituent, more preferably a linear or branched saturated aliphatic hydrocarbon group, and even more preferably a linear saturated aliphatic hydrocarbon group.

[0019] R 2 From the viewpoint of facilitating detection by an analytical device, is preferably a hydrocarbon group having no substituent, more preferably an aromatic hydrocarbon group, and even more preferably a phenylene group.

[0020] R 1 , and R 2The number of carbon atoms in the hydrocarbon group (not including the number of carbon atoms in the substituents) is not particularly limited, but from the viewpoint of facilitating detection by an analytical device, in the case of a linear aliphatic saturated hydrocarbon group, it is 1 or more, preferably 2 or more, and preferably 12 or less, more preferably 8 or less; in the case of a linear unsaturated hydrocarbon group, it is 2 or more, preferably 3 or more, and preferably 12 or less, more preferably 8 or less; in the case of a branched aliphatic saturated or unsaturated hydrocarbon group, it is 3 or more, preferably 4 or more, and preferably 12 or less, more preferably 8 or less; and in the case of an alicyclic saturated or unsaturated hydrocarbon group or an aromatic hydrocarbon group, it is preferably 6 or more, and preferably 14 or less, more preferably 10 or less.

[0021] R 3 , R 4 , and R 5 From the viewpoint of facilitating detection by an analytical device, is preferably a hydrocarbon group having no substituent, more preferably a linear or branched saturated aliphatic hydrocarbon group, and even more preferably a linear saturated aliphatic hydrocarbon group.

[0022] R 3 , R 4 , and R 5 The number of carbon atoms in the hydrocarbon group (not including the number of carbon atoms in the substituents) is not particularly limited, but from the viewpoint of facilitating detection by an analytical device, in the case of a linear aliphatic saturated hydrocarbon group, it is 1 or more, preferably 2 or more, and preferably 12 or less, and more preferably 6 or less; in the case of a linear unsaturated hydrocarbon group, it is 2 or more, preferably 3 or more, and preferably 12 or less, and more preferably 6 or less; in the case of a branched aliphatic saturated or unsaturated hydrocarbon group, it is 3 or more, preferably 4 or more, and preferably 12 or less, and more preferably 6 or less; and in the case of an alicyclic saturated or unsaturated hydrocarbon group or an aromatic hydrocarbon group, it is preferably 6 or more, and preferably 14 or less, and more preferably 10 or less.

[0023] A is a functional group containing a single bond between a heteroatom and a carbon atom, and the single bond is cleaved by heating or the like. By introducing the functional group, fragment ions derived from the organic compound can be detected, enabling highly selective and sensitive analysis. Examples of the functional group include an amide bond, an ester bond, an ether bond, a urethane bond, and a urea bond. From the viewpoint of highly selective detection of the reactant, the functional group is preferably an amide bond.

[0024] Y - is an anion, e.g., a halogen anion, ClO4 - , BF4 - , PF6 - , CH3COO - , CF3COO - , and CH3(C6H4)SO3 - Examples include:

[0025] Specific examples of the organic compound represented by the above chemical formula (1) include the following compounds. [ka]

[0026] The organic compound represented by the chemical formula (1) can be easily synthesized using known raw materials and reaction reagents in accordance with general-purpose chemical reactions. For example, the TMAS and TMAA can be synthesized by the following chemical reactions using the following raw materials and reaction reagents. Detailed methods for synthesizing TMAS and TMAA are shown in the examples. Those skilled in the art will be able to easily synthesize organic compounds represented by the chemical formula (1) other than the above TMAS and TMAA in accordance with general-purpose chemical reactions using appropriate raw materials and reaction reagents.

[0027] [ka]

[0028] In the above reaction scheme, DMT-MM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride) is a condensing agent, TCEP (tris(2-carboxyethyl)phosphine) is a reducing agent, and TFA is trifluoroacetic acid.

[0029] [ka]

[0030] In the above reaction scheme, DMT-MM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride) is a condensing agent, Boc is a t-butoxycarbonyl group, and TFA is trifluoroacetic acid.

[0031] The organic compound of the present invention can be used, for example, for evaluating the skin sensitization of trace amounts of chemical substances (such as skin sensitizers) and for quantitatively measuring trace amounts of chemical substances. From the viewpoint of microanalysis, the organic compound of the present invention can be preferably used as a labeling reagent for detecting trace amounts of chemical substances (such as skin sensitizers), more preferably as a labeling reagent for mass spectrometry, and even more preferably as a labeling reagent for mass spectrometry of skin sensitizers.

[0032] <Reagents> The reagent of the present invention may consist solely of the organic compound, or may contain one or more additives in addition to the organic compound as the main measurement agent. Examples of additives include pH adjusters and stabilizers. The reagent of the present invention may also be prepared by dissolving the organic compound and, if necessary, the additives in water, an aqueous buffer solution, an organic solvent, or a mixture of these solvents. The reagent of the present invention may be in the form of a solution, liquid, or solid (powder, granules, lyophilized product, tablet, etc.).

[0033] The reagent of the present invention can be used, for example, for evaluating the skin sensitization of trace amounts of chemical substances (such as skin sensitizers) and for quantitatively measuring trace amounts of chemical substances. From the viewpoint of microanalysis, the reagent of the present invention can be preferably used as a labeling reagent for detecting trace amounts of chemical substances (such as skin sensitizers), more preferably as a labeling reagent for mass spectrometry, and even more preferably as a labeling reagent for mass spectrometry of skin sensitizers.

[0034] <Analysis method> The analytical method of the present invention involves reacting the organic compound with a chemical substance (test substance) to obtain a reaction product, and then separating and detecting the reaction product. The analytical method of the present invention will be described below with specific examples.

[0035] The chemical substance (test substance) is not particularly limited as long as it is reactive to the thiol group or amino group of the organic compound or reacts with the thiol group or amino group of the organic compound, but is preferably a sensitizing substance, more preferably a skin sensitizing substance.

[0036] The reagent containing the organic compound is used as an aqueous buffer solution containing, for example, an organic acid salt such as ammonium acetate or an inorganic salt such as a phosphate, or as a mixed solvent buffer solution in which the organic compound is dissolved in water or a mixed solvent of these with an organic solvent. The concentration of the organic compound in the aqueous buffer solution or mixed solvent buffer solution is not particularly limited, but is, for example, about 0.01 μM to 1 M, and usually about 0.1 mM to 500 mM.

[0037] The chemical substance (test substance) is dissolved in an organic solvent such as methanol, ethanol, acetonitrile, or acetone, or a mixed solvent thereof, to a concentration of, for example, about 0.01 μM to 1 M, typically about 0.1 mM to 500 mM.

[0038] Next, the aqueous buffer solution or the mixed solvent buffer solution containing the reagent is mixed with a test substance solution containing the test substance so that the molar concentration ratio of the organic compound to the test substance is, for example, 1:100 to 10:1, and the organic compound is reacted with the test substance to obtain a reaction product. The reaction can be carried out by stirring or leaving the mixture to stand, usually for about 1 minute to 2 days, while keeping the mixture at a temperature, for example, in the range of about 4°C to 60°C.

[0039] Thereafter, the produced reaction product is separated and detected. The method for separating the reaction product is not particularly limited, but is preferably chromatography from the viewpoint of excellent separation and detectability. Examples of the chromatography include supercritical chromatography, ion chromatography, liquid chromatography, gas chromatography, and thin layer chromatography. From the viewpoint of excellent detectability, supercritical chromatography, ion chromatography, or liquid chromatography is preferable, and liquid chromatography is more preferable.

[0040] Examples of liquid chromatography include normal phase chromatography, reverse phase chromatography, size exclusion chromatography, and ion exchange chromatography. From the viewpoint of excellent detectability, reverse phase chromatography or ion exchange chromatography is preferred, and reverse phase chromatography is more preferred.

[0041] The method for detecting the reaction product is not particularly limited, and examples thereof include spectroscopic analysis using ultraviolet light, visible light, or infrared light, mass spectrometry, fluorescence analysis, differential refractive index analysis, electrical conductivity analysis, and evaporative light scattering analysis, and from the viewpoint of trace analysis, mass spectrometry is preferred.

[0042] The mass spectrometry method is not particularly limited as long as it is an analytical method that utilizes mass analysis, and examples thereof include ordinary mass spectrum acquisition methods; selected ion monitoring methods; and tandem mass spectrometry methods (MS / MS methods) such as data-dependent acquisition methods, data-independent acquisition methods, precursor ion scanning methods, selected reaction monitoring methods, and constant neutral scanning methods. From the viewpoint of trace analysis, tandem mass spectrometry methods (MS / MS methods) are preferred.

[0043] Examples of MS / MS methods include selected reaction monitoring, precursor ion scan, and constant neutral loss scan. Methods that will be developed in the future can also be used as long as they are analytical methods included in the MS / MS method.

[0044] According to the present invention, test substances such as skin sensitizers can be analyzed simply, sensitively, and accurately by using a specific labeling reagent to enhance selectivity. In particular, test substances can be quantitatively analyzed by mass spectrometry such as MS / MS. Furthermore, multiple test substances can be measured simultaneously.

[0045] The analytical method of the present invention is extremely useful because it can be widely used in industry, particularly in the fields of cosmetics, daily necessities, pharmaceuticals, and analytical instruments. [Example]

[0046] The present invention will be specifically described below with reference to examples.

[0047] Synthesis Example 1 Synthesis of TMAS (4-TriMethylAmmoniobenzoyl 2-Sulfanylethylamine) [ka] 4-Aminobenzoic acid (200 mg, 1.46 mmol) was placed in a 30 mL screw tube and dissolved in DMSO (3 mL). The resulting solution was ice-cooled, and iodomethane (726 μL, 8.0 eq.) was added dropwise with stirring. After the addition was complete, the mixture was returned to room temperature (25°C) and left overnight (approximately 20 hours). The resulting reaction solution was ice-cooled, and 0.5 M KOHaq was added to terminate the reaction and hydrolyze the mixture. After 20 minutes, the mixture was neutralized with hydrochloric acid and washed with ethyl acetate to obtain an aqueous solution containing potassium 4-trimethylammonium benzoate. [ka] A portion of the collected aqueous layer (equivalent to 0.1 mmol) was removed and placed in a 20 mL screw tube. MeOH (2 mL) was added, followed by cystamine dihydrochloride (11.3 mg, 0.05 mmol) and DMT-MM (42.0 mg, 0.15 mmol), and the mixture was allowed to react overnight (approximately 20 hours) at room temperature (25°C). An appropriate amount of TCEP was added to the resulting reaction solution to reduce the disulfide bond. The insoluble matter was filtered and concentrated, and the mixture was purified by HPLC (0.1% TFA aqueous solution was used as the eluent for the separation and purification of the target product). The obtained fraction was freeze-dried to obtain the target product, TMAS. 1 The 1 H NMR data was as follows: 1 H NMR(D2O): δ7.89(m,4H),3.49(s,9H),2.80(t,2H),2.62(t,2H)

[0048] Synthesis Example 2 Synthesis of TMAA (4-TriMethylAmmoniobenzoyl 6-Aminohexylamine) An aqueous solution containing potassium 4-trimethylammonium benzoate was obtained in the same manner as in Synthesis Example 1. [ka] A portion of the collected aqueous layer (equivalent to 0.1 mmol) was removed and placed in a 20 mL screw tube. MeOH (2 mL) was added, followed by N-Boc-1,6-diaminohexane (26.0 mg, 0.12 mmol) and DMT-MM (42.0 mg, 0.15 mmol), and the mixture was allowed to react overnight (approximately 20 hours) at room temperature (25°C). The resulting reaction solution was concentrated to dryness, and 10% TFA aqueous solution (2 mL) was added to deprotect the Boc group. The insoluble matter was filtered and concentrated, and then purified by HPLC. The resulting fraction was freeze-dried to obtain the target product, TMAA. 1 The 1 H NMR data was as follows: 1 H NMR(D2O): δ7.96(m,4H),3.66(s,9H),3.40(t,2H),2.98(t,2H),1.63(br,4H),1.42(br,2H)

[0049] The following drugs were used in the following test examples. (Labeling Reagent) TMAS Compound obtained in Synthesis Example 1 TMAA Compound obtained in Synthesis Example 2 Cysteine ​​peptide (hereinafter also referred to as Cys-P) - a compound sold by RS synthesis NAC obtained from Fujifilm Wako Pure Chemical Industries as ADRA kit (Sensitizing compound, skin sensitization: strength) Benzoyl peroxide (molecular weight 242.23) obtained from Tokyo Chemical Industry Co., Ltd. Diphenylcyclopropenone (molecular weight 206.24) obtained from Fujifilm Wako Pure Chemical Industries ·CMI / MI (5-Chloro-2-methyl-4-isothiazolin-3-one / 2-methyl-4-isothiazolin-3-one) (skin sensitization: strong) (CMI molecular weight 149.59, MI molecular weight 115.15) Obtained from Fluorochem Cinnamaldehyde (molecular weight 132.16) obtained from Fujifilm Wako Pure Chemical Industries Trimellitic anhydride (molecular weight 192.13) obtained from Fujifilm Wako Pure Chemical Industries p-Benzoquinone (molecular weight 108.09) obtained from Fujifilm Wako Pure Chemical Industries Formaldehyde (molecular weight 30.03) Formaldehyde solution obtained from Fujifilm Wako Pure Chemical Industries Oxazolone 4-ethoxymethylene-2-phenyloxazolin-5-one (molecular weight 217.22) obtained from Fujifilm Wako Pure Chemical Industries Palmitoyl chloride (molecular weight 274.87) obtained from Tokyo Chemical Industry Co., Ltd. The above-mentioned skin sensitization potential is an evaluation result based on the LLNA test (a test using mice) described in the aforementioned Non-Patent Document 1 (GF Gerberick et al., Toxicol. Sci., 97(2), 417-427:2007).

[0050] Test Example 1: Evaluation of detection sensitivity of reaction products with sensitizing compounds (1) About TMAS (the present invention) [Preparation of TMAS solution] 12.5 mg of TMAS (molecular weight 337.38) was weighed out and dissolved in 100 mM phosphate (sodium) buffer (pH = 8.0), and the volume was adjusted to 100 mL (125 mg / L solution).

[0051] (2) Cys-P (Comparative Example) [Preparation of Cys-P solution] 12.5 mg of the cysteine ​​peptide (Ac-Arg-Phe-Ala-Ala-Cys-Ala-Ala-COOH: hereinafter Cys-P) (molecular weight 750.87) described in Non-Patent Document 1 (GF Gerberick et al., Toxicol. Sci., 97(2), 417-427:2007) was weighed out and dissolved in 100 mM sodium phosphate buffer (pH = 8.0), and the volume was adjusted to 100 mL (125 mg / L solution).

[0052] (3) NAC (Comparative Example) [Preparation of NAC solution] To a reagent bottle containing 14.5 μg of N-(2-(1-naphthyl)acetyl)-L-cysteine ​​(hereinafter also referred to as NAC) (molecular weight 289.34) described in Patent Document 2 (JP 2011-59102 A), 1 mL of 100 mM phosphate (sodium) buffer (pH = 8.0) was added and dissolved (14.5 mg / L solution).

[0053] [Preparation of reaction solution] 600 μL of a 125 mg / L solution of TMAS, Cys-P, or NAC and 150 μL of a 50 μg / L or 5000 μg / L solution of the test substance (cinnamaldehyde) in acetonitrile were added to a 1 mL vial and stirred (water / solvent = 80 / 20). This mixture was reacted at room temperature for 24 hours and then subjected to HPLC under the conditions described below.

[0054] [HPLC measurement conditions] Equipment: Agilent 1290 Series (Agilent), TripleTOF 6600 (Sciex) Column: Kinetex polar C18 (2.1 mm x 150 mm, 2.6 μm) Column temperature: 40℃ Flow rate: 0.15ml / min. Detection: ESI(+) Detection method: High Resolution Multiple Reaction Monitoring Measurement mass range: MS (depending on reaction product), MS / MS (m / z 100-1000) Eluent A: Ultrapure water (0.1% formic acid) Eluent B: Acetonitrile (0.1% formic acid) Elution conditions: gradient as follows [Table 1] Injection volume: 2μl Analysis time: 30 minutes

[0055] [Measurement results] The chromatograms are shown in Figure 1. Comparing the S / N ratios of the test substance at 50 μg / L, TMAS was approximately 60, while Cys-P and NAC were not detected. Comparing the S / N ratios of the test substance at 5000 μg / L, TMAS was approximately 6000, Cys-P was approximately 20, and NAC was approximately 110, demonstrating that TMAS can be detected with sensitivity several tens to several hundreds times higher than that of Cys-P and NAC.

[0056] Test Example 2: Evaluation of reactivity with sensitizing compounds and detection sensitivity of reactants [Test substance] Using the compounds listed in Table 3 as sensitizing compounds, skin sensitization was measured according to the method described below.

[0057] (1) About TMAS (the present invention) [Preparation of TMAS solution] A TMAS solution was prepared in the same manner as in Test Example 1 above.

[0058] [Preparation of reaction solution] A reaction solution was prepared in the same manner as in Test Example 1 above.

[0059] [HPLC measurement conditions] Equipment: Agilent 1290 Series (Agilent), TripleTOF 6600 (Sciex) Column: Kinetex polar C18 (2.1 mm x 150 mm, 2.6 μm) Column temperature: 40℃ Flow rate: 0.25ml / min. Detection: ESI (+) m / z 70-1300 Detection Method: Information Dependent Acquisition Measurement mass range: TOF MS (m / z 70-1300), MS / MS (m / z 70-1300) Eluent A: Ultrapure water (0.1% formic acid) Eluent B: Acetonitrile (0.1% formic acid) Elution conditions: gradient as follows [Table 2]

[0060] The S / N ratio was calculated, and the concentration (μg / L) was determined with an S / N ratio of 3 as the detection limit. The results are shown in Table 3.

[0061] [Table 3]

[0062] Test Example 3: Evaluation of reactivity with sensitizing compounds and detection sensitivity of reactants [Test substance] Using the compounds listed in Table 4 as sensitizing compounds, skin sensitization was measured according to the method described below. (2) Regarding TMAA (the present invention) [Preparation of TMAA solution] 12.5 mg of TMAA (molecular weight 505.46) was weighed out, dissolved in 100 mM phosphate (sodium) buffer (pH = 10.2), and the solution was adjusted to a final volume of 100 mL (125 mg / L solution).

[0063] [Preparation of reaction solution] A reaction solution was prepared in the same manner as in Test Example 1 above.

[0064] [HPLC measurement conditions] Same as Test Example 1 above.

[0065] The S / N ratio was calculated, and the concentration (μg / L) was determined with an S / N ratio of 3 as the detection limit. The results are shown in Table 4.

[0066] [Table 4] [Industrial Applicability]

[0067] The organic compound, reagent, and analytical method of the present invention are suitable for use in evaluating the skin sensitization potential of trace amounts of chemical substances and for quantitatively measuring trace amounts of chemical substances.

Claims

1. An organic compound represented by the following chemical formula (1): 【Chemistry 1】 (wherein X is a thiol group or an amino group, and R １ is a chain aliphatic hydrocarbon group having 1 to 12 carbon atoms, R ２ is an aromatic hydrocarbon group having 6 to 10 carbon atoms, R ３ , R ４ , and R ５ are each independently a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, A is an amide bond, and Y － is a halogen anion, ClO ４ － , B.F. ４ － , P.F. ６ － , C.F. ３ COO － , and C.H. ３ (C ６ H ４ ) SO ３ － is an anion selected from

2. The R ２ The organic compound according to claim 1 , wherein is a phenylene group.

3. 2. The organic compound according to claim 1, wherein the compound is a salt of 4-TriMethylAmmoniobenzoyl 2-Sulfanylethylamine and an anion, or a salt of 4-TriMethylAmmoniobenzoyl 6-Aminohexylamine and an anion.

4. A reagent containing the organic compound according to any one of claims 1 to 3.

5. An analytical method comprising reacting the organic compound according to any one of claims 1 to 3 with a chemical substance to obtain a reaction product, and then separating and detecting the reaction product.

6. 6. The analytical method according to claim 5, wherein the chemical substance is reactive with a thiol group or an amino group of the organic compound.

7. 7. The analytical method according to claim 5, wherein the chemical substance reacts with a thiol group or an amino group of the organic compound.

8. The analytical method according to any one of claims 5 to 7, wherein the separation method is chromatography.

9. 9. The analytical method according to claim 5, wherein the detection method is mass spectrometry.

10. 10. The analytical method according to claim 5, wherein the chemical substance is a sensitizing substance.

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