Reagent for measuring biological sample containing amines or alcohols, and method for suppressing increase in oxidative condensation ability

Abstract

To provide a method for suppressing an increase in oxidative condensation ability caused by a peroxide or the like contained in a surfactant in a reagent for measuring a biological sample, and to provide the reagent for measuring the biological sample using the method.SOLUTION: Amines or alcohols are contained in the reagent for measuring the biological sample.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a biological sample measurement reagent containing amines or alcohols to suppress an increase in oxidative condensation activity. The present invention also relates to a method for suppressing an increase in oxidative condensation activity in a biological sample measurement reagent containing amines or alcohols. The present invention is particularly useful in the fields of chemistry, life science, analytical science, clinical testing, etc. [Background technology]

[0002] Because various metals exist in the body and each exerts a variety of functions, measuring metal concentrations in biological samples and observing their fluctuations is essential for the diagnosis, treatment, early detection, and prevention of diseases, and is widely performed in hospitals, testing facilities, etc. For example, zinc deficiency is known to cause symptoms such as growth disorders and taste disorders, so if these symptoms are observed, serum zinc concentrations may be measured.

[0003] Known methods for measuring zinc include atomic absorption spectrometry, inductively coupled plasma (ICP) emission spectrometry, and colorimetric assays. Among these, colorimetric assays using chelating colorants utilize the change in absorbance that occurs when zinc forms a chelate with a chelating colorant, such as 2-(5-bromo-2-pyridylazo)-5(N-propyl-N-sulfopropylamino)phenol sodium (hereinafter sometimes abbreviated as 5-Br-PAPS) or 2-(5-nitro-2-pyridylazo)-5(N-propyl-N-sulfopropylamino)phenol sodium (hereinafter sometimes abbreviated as nitro-PAPS). This assay allows the measurement of zinc concentrations in biological samples using general-purpose automated analyzers, even without an atomic absorption spectrophotometer, and is widely used in hospital laboratories.

[0004] However, when measuring biological materials as samples, the samples may contain many substances that are not the target of measurement, which raises concerns that these substances may adversely affect the measurement. If such adverse effects occur, problems such as the inability to accurately measure the concentration of the target substance can arise. This effect is called the effect of coexisting substances, and known examples of such substances include hemoglobin. To prevent this effect, known methods for suppressing interference include the addition of a carboxylic acid or its salt and / or an anionic surfactant (see Patent Document 1), and an interference avoidance agent containing a nonionic surfactant as an active ingredient (see Patent Document 2). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2020-048431 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-119729 Summary of the Invention [Problem to be solved by the invention]

[0006] While conducting research on biological sample measurement reagents, the inventors encountered a phenomenon in which the magnitude of the effect of hemoglobin on the measured value of the substance to be measured changes over time after the biological sample measurement reagent is prepared. In such cases, there are problems such as an inaccurate measurement value being obtained or the measurement itself being impossible.

[0007] The inability to obtain accurate measurements, or the inability to perform measurements at all, is a serious problem that can lead to erroneous or delayed diagnosis of disease. There is a demand for biological sample measurement reagents that can obtain accurate measurements. Therefore, there is a demand for biological sample measurement reagents that do not cause changes in the magnitude of the influence of hemoglobin on the measurement values ​​of the substance to be measured. [Means for solving the problem]

[0008] As a result of intensive research into the above-mentioned problems and methods for solving them, the inventors discovered that changes in the oxidative condensation ability of a biological sample measurement reagent also change the magnitude of the influence of hemoglobin on the measurement value of the substance being measured.Furthermore, they found that the increase in oxidative condensation ability can be suppressed by adding certain compounds to the biological sample measurement reagent, and thus completed the present invention.

[0009] That is, the present invention is as follows. (1) A biological sample measurement reagent characterized by containing amines or alcohols for the purpose of suppressing an increase in oxidative condensation ability. (2) The reagent according to (1) above, wherein the increase in oxidative condensation ability is due to a surfactant. (3) The reagent according to (1) or (2) above, wherein the amine or alcohol is an alkanolamine. (4) The reagent according to (1) or (2) above, wherein the biological sample measurement reagent is a biochemical test reagent. (5) The reagent according to (3) above, wherein the biological sample measurement reagent is a biochemical test reagent. (6) The reagent according to (4) above, wherein the biological sample measurement reagent is a zinc measurement reagent. (7) The reagent according to (5) above, wherein the biological sample measurement reagent is a zinc measurement reagent. (8) A method for suppressing an increase in oxidative condensation activity in a biological sample measurement reagent, characterized by containing amines and / or alcohols. (9) The method according to (8) above, wherein the increase in oxidative condensation ability is due to a surfactant. (10) The method according to (8) or (9) above, wherein the amines or alcohols are alkanolamines. (11) The method according to (8) or (9) above, wherein the biological sample measurement reagent is a biochemical test reagent. (12) The method according to (10) above, wherein the biological sample measurement reagent is a biochemical test reagent. (13) The method according to (11) above, wherein the biological sample measurement reagent is a zinc measurement reagent. (14) The method according to (12) above, wherein the biological sample measurement reagent is a zinc measurement reagent. [Effects of the Invention]

[0010] According to the present invention, an increase in oxidative condensation activity can be suppressed, and therefore, changes in the magnitude of the influence of hemoglobin on the measured value of the substance to be measured can be suppressed, thereby enabling accurate measured values ​​to be obtained. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will be described in detail below. The following embodiments are merely examples for explaining the present invention, and are not intended to limit the present invention to these embodiments. The present invention can be embodied in various forms without departing from the gist of the present invention.

[0012] 1. Overview When measuring biological samples, the sample may contain many substances that are not the target of measurement, and there is a concern that these substances may adversely affect the measurement. If such adverse effects occur, problems such as the inability to accurately measure the concentration of the target substance may occur. This effect is called the effect of coexisting substances, and hemoglobin is known to be an example of such an effect. While conducting research on biological sample measurement reagents, the inventors encountered a phenomenon in which the magnitude of the effect of hemoglobin on the measured value of the substance to be measured changes over time after the biological sample measurement reagent is prepared. In such cases, there are problems such as an inaccurate measurement value being obtained or the measurement itself being impossible. The inability to obtain accurate measurements, or the inability to perform measurements at all, is a serious problem that can lead to erroneous or delayed diagnosis of disease. There is a demand for biological sample measurement reagents that can obtain accurate measurements. Therefore, there is a demand for biological sample measurement reagents that do not cause changes in the magnitude of the influence of hemoglobin on the measurement values ​​of the substance to be measured. As a result of intensive research into the above-mentioned problems and methods for solving them, the inventors discovered that changes in the oxidative condensation ability of a biological sample measurement reagent also change the magnitude of the influence of hemoglobin on the measurement value of the substance being measured, and further found that the increase in oxidative condensation ability can be suppressed by adding certain compounds to the biological sample measurement reagent. The present invention was made based on this finding.

[0013] 2. Oxidative condensation ability In the present invention, the oxidative condensation ability refers to the strength of an oxidative condensation reaction. For example, peroxides can cause oxidative condensation reactions, so measuring the oxidative condensation ability of a sample can be used as a method for evaluating the peroxides contained in the sample. An example of an oxidative condensation reaction is the oxidative condensation reaction in which a coupler such as 4-aminoantipyrine and a hydrogen donor such as N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3-methoxyaniline (hereinafter sometimes abbreviated as ADOS) undergo oxidative condensation in the presence of a peroxide such as hydrogen peroxide and peroxidase, which is also known as the Trinder reaction.

[0014] There are several methods for measuring the oxidative condensation ability, but the measurement method in the present invention is as follows. a. Preparation of oxidative condensation activity measurement reagent Dissolve the following components in purified water to the concentrations indicated, and adjust the pH to 7.35 (20°C) to prepare a reagent for measuring oxidative condensation activity. N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (hereinafter sometimes abbreviated as TES) (Actec) 68.78g / L ADOS (Dojindo Chemical Research Institute) 0.53g / L 4-aminoantipyrine (Actec) 0.10g / L Peroxidase (Toyobo) 23kU / L b. Preparation of standard sample (100 μM hydrogen peroxide aqueous solution) A standard sample is prepared by dissolving hydrogen peroxide (30%) (Kanto Chemical) in pure water to a concentration of 100 μM. c.Measurement method Measurements can be performed using a spectrophotometer or general-purpose automated analyzer, but this example uses a general-purpose automated analyzer, the Canon Medical Systems TBA-120FR Sora Edition. 9 μL of the sample to be measured for oxidative condensation activity (measurement sample) is mixed with 200 μL of the oxidative condensation activity measurement reagent, and the mixture is incubated at 37°C for 10 minutes. The absorbance at 546 nm is then subtracted from the absorbance at 750 nm to determine the absorbance. By proportionally calculating this value and the value obtained when a standard sample is used instead of the measurement sample, the oxidative condensation activity of the measurement sample can be calculated as a value converted into the concentration of aqueous hydrogen peroxide.

[0015] There are various possible causes for an increase in oxidative condensation capacity. For example, compounds may convert to peroxides over time, and this change is thought to increase the oxidative condensation capacity. This change is thought to be influenced by temperature, exposure to light, storage time, and other factors. Furthermore, depending on the amount of peroxide in the compound, further peroxides may be generated. Therefore, in the case of compounds for which the peroxide content is not specified in the product specifications, even if the product name is the same, differences in the magnitude and speed of the increase in oxidative condensation capacity may occur depending on the production lot. When such products are purchased and used to prepare reagents, differences in performance due to differences in production lots may occur. The present invention suppresses the increase in oxidative condensation capacity, and is therefore thought to also have the effect of suppressing such differences due to production lots.

[0016] Substances that may cause an increase in the oxidative condensation ability of a biological sample measurement reagent are not particularly limited as long as they have such properties, and examples thereof include surfactants. Examples of surfactants include cationic surfactants, anionic surfactants, amphoteric surfactants, and nonionic surfactants, but any of these may be used. Furthermore, the surfactant may have a polyoxyethylene chain. Examples of such surfactants include polyoxyalkylene ether compounds such as polyoxyethylene alkyl ethers, polyoxypropylene alkyl ethers, polyoxypropylene alkylphenyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene polystyrylphenyl ethers, polyoxyethylene polybenzylphenyl ethers, polyoxyethylene polyoxypropylene glycol, polyoxyethylene sterols, polyoxyethylene hydrogenated sterols, polyoxyethylene lanolin, and beeswax derivatives; polyhydric alcohol partial ester compounds such as glycerin fatty acid partial esters, sorbitan fatty acid partial esters, pentaerythritol fatty acid partial esters, propylene glycol monofatty acid esters, and sucrose fatty acid partial esters; and polyoxyethylenated polyhydric alcohol fatty acid esters such as polyoxyethylene sorbitan fatty acid partial esters, polyoxyethylene sorbitol fatty acid partial esters, polyoxyethylene glycerin fatty acid partial esters, polyethylene glycol fatty acid esters, polyglycerin fatty acid partial esters, and polyoxyethylenated castor oil.

[0017] 3. Amines or alcohols The amines or alcohols contained in the biological sample measurement reagent of the present invention are not particularly limited as long as they have the effect of suppressing an increase in oxidative condensation ability, and examples include primary amines, secondary amines, tertiary amines, aliphatic amines, aromatic amines, heterocyclic amines, primary alcohols, secondary alcohols, tertiary alcohols, monohydric alcohols, dihydric alcohols, trihydric alcohols, etc. Compounds having both an amino group and a hydroxy group may also be used, such as alkanolamines. Among these, ethanol, 2-propanol, glycerin, 2-aminoethanol, DL-1-amino-2-propanol, 2-(2-aminoethoxy)ethanol, 3-amino-1,2-propanediol, bistrispropane (hereinafter sometimes abbreviated as BTP), 2-(methylamino)ethanol, diethanolamine, triisopropanolamine (hereinafter sometimes abbreviated as TIPA), N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine (hereinafter sometimes abbreviated as THEED), N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine (hereinafter sometimes abbreviated as EDTP), and ethylenediamine-N,N,N',N'-tetraacetic acid disodium salt dihydrate (hereinafter sometimes abbreviated as EDTA) are particularly preferred. Note that amines or alcohols may be added for purposes other than obtaining the effects of the above-mentioned actions.

[0018] The biological sample measurement reagent may contain at least one type of amine or alcohol, but may contain two or more types.

[0019] The concentration of amines or alcohols contained in the biological sample measurement reagent is not particularly limited as long as it is a concentration that exhibits the effect of suppressing an increase in oxidative condensation ability. The lower limit of the concentration of amines or alcohols is preferably 0.00001 mM, particularly preferably 0.001 mM, and even more preferably 0.1 mM. The upper limit is preferably 1000 mM, particularly preferably 800 mM, and further preferably 300 mM. Regarding the concentration of the amines or alcohols, for example, when the lower limit is 0.00001 mM, the concentration can be 0.00001 mM to 300 mM, 0.00001 mM to 800 mM, or 0.00001 mM to 1000 mM; when the lower limit is 0.001 mM, the concentration can be 0.001 mM to 300 mM, 0.001 mM to 800 mM, or 0.001 mM to 1000 mM; and when the lower limit is 0.1 mM, the concentration can be 0.1 mM to 300 mM, 0.1 mM to 800 mM, or 0.1 mM to 1000 mM.

[0020] When the biological sample measurement reagent is composed of multiple reagents, the amines or alcohols may be contained in at least the reagent in which an increase in oxidative condensation ability is desired to be suppressed, and may also be contained in the other reagents.

[0021] 4. Biological sample measurement reagents In the present invention, a biological sample measurement reagent refers to one that can measure enzyme activity, substance concentration, etc. in a biological sample, and is not particularly limited as long as it is capable of doing so. Biological sample measurement reagents include biochemical biological sample measurement reagents that utilize biochemical reactions, immunological biological sample measurement reagents that utilize antigen-antibody reactions, and genetic biological sample measurement reagents that utilize gene analysis techniques, but in the present invention, biochemical biological sample measurement reagents are preferred. Examples of biochemical biological measurement reagents include zinc measurement reagents.

[0022] The biological sample measurement reagent of the present invention may be one that performs measurement by an end-point method or a reaction rate method, and may be selected appropriately.

[0023] The biological sample measurement reagent of the present invention may be a one-reagent method in which a biological sample is mixed with one reagent to perform measurement, a two-reagent method in which a biological sample is mixed with two reagents simultaneously or in an appropriate order to perform measurement, or a multi-reagent method in which a biological sample is mixed with three or more reagents simultaneously or in an appropriate order to perform measurement, and can be selected as appropriate.

[0024] In the biological measurement reagent of the present invention, the measurement may be performed manually or using an apparatus such as a general-purpose automatic analyzer.

[0025] All or some of the constituent reagents of the biological sample measurement reagent of the present invention may be liquid reagents.

[0026] The biological sample measurement reagent of the present invention can be sold alone or used to measure a target substance in a biological sample.

[0027] The biological sample measurement reagent of the present invention can be sold in combination with other reagents other than the above-mentioned biological sample measurement reagent, or can be used to measure a substance to be measured in a biological sample. Examples of other reagents other than the above-mentioned biological sample measurement reagent include buffer solutions, sample dilutions, reagent dilutions, reagents containing substances for calibration, and reagents containing substances for quality control.

[0028] The biological sample measurement reagent of the present invention may be a biological sample measurement reagent kit consisting of multiple constituent reagents such as a first reagent and a second reagent, or other reagents.

[0029] The pH of the biological sample measurement reagent of the present invention can be selected appropriately, taking into consideration the stability of the components during storage, the reaction rate during biological sample measurement, etc. Furthermore, when the biological sample measurement reagent is composed of multiple reagents, the pH of each reagent that makes up the biological sample measurement reagent can be selected appropriately, taking into consideration the stability of the components during storage, the reaction rate during measurement of the measurement sample, etc.

[0030] For example, in the case of a zinc measurement reagent, the lower limit of the pH when measuring the zinc concentration in a sample is preferably 7.0, and particularly preferably 8.0. The upper limit is preferably 11.0, and particularly preferably 10.0. Regarding the pH of this zinc measurement reagent, if the lower limit is 7.0, the pH may be 7.0 to 10.0 or 7.0 to 11.0, and if the lower limit is 8.0, the pH may be 8.0 to 10.0 or 8.0 to 11.0.

[0031] In addition to amines or alcohols, the biological sample measurement reagent of the present invention may contain known surfactants, buffers, enzymes, coenzymes, reaction substrates, pH adjusters, preservatives, etc. as needed. The concentration of each of these components can be selected appropriately, taking into consideration the stability of the components during storage, the reaction rate during biological sample measurement, etc. When the biological sample measurement reagent is composed of multiple reagents, the concentration of each of these components in each reagent that makes up the biological sample measurement reagent can be selected appropriately, taking into consideration the stability of the components during storage, the reaction rate during biological sample measurement, etc.The buffering agent is not particularly limited, and examples thereof include acetic acid, citric acid, tartaric acid, carbonic acid, boric acid, phosphoric acid, trishydroxymethylaminomethane, imidazole, glycylglycine, bistris, tricine, bicine, BTP, TES, 2-morpholinoethanesulfonic acid (hereinafter sometimes abbreviated as MES), N-(2-acetamido)iminodiacetic acid (hereinafter sometimes abbreviated as ADA), N-(2-acetamido)-2-aminoethanesulfonic acid (hereinafter sometimes abbreviated as ACES), piperazine-1,4-bis(2-ethanesulfonic acid), and the like. N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (hereinafter sometimes abbreviated as BES), 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid (hereinafter sometimes abbreviated as HEPES), 3-[N,N-bis(2-hydroxyethyl)amino]-2- Hydroxypropanesulfonic acid (hereinafter sometimes abbreviated as DIPSO), 3-[N-tris(hydroxymethyl)methylamino]-2-hydroxypropanesulfonic acid (hereinafter sometimes abbreviated as TAPSO), piperazine-1,4-bis(2-hydroxypropanesulfonic acid) (hereinafter sometimes abbreviated as POPSO), N-(2-hydroxyethyl)piperazine-N'-(3-propanesulfonic acid) (hereinafter sometimes abbreviated as HEPPS), 4-(2-hydroxyethyl)piperazine-1-(2-hydroxypropane- 3-sulfonic acid) (hereinafter sometimes abbreviated as HEPPSO), N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (hereinafter sometimes abbreviated as TAPS), 2-cyclohexylaminoethanesulfonic acid (hereinafter sometimes abbreviated as CHES), 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid (hereinafter sometimes abbreviated as CAPSO), N-cyclohexyl-3-aminopropanesulfonic acid (hereinafter sometimes abbreviated as CAPS), or salts thereof.

[0032] 5. Biological Samples In the present invention, a biological sample is a sample that is the subject of measurement of enzyme activity, substance concentration, etc. contained in a living organism, and is not particularly limited as long as it is such a sample. Examples of such biological samples include human or animal blood, serum, plasma, urine, feces, semen, cerebrospinal fluid, saliva, sweat, tears, ascites, amniotic fluid, extracts of organs such as the brain, tissues and cells such as hair, skin, nails, muscles or nerves, etc.

[0033] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. [Example]

[0034] [Example 1] (Confirmation of the effect of amines or alcohols in inhibiting an increase in oxidative condensation ability) The oxidative condensation ability was measured in a solution containing amines or alcohols, and the effect of amines or alcohols in suppressing an increase in the oxidative condensation ability was confirmed.

[0035] 1. Solution Preparation

[0036] (1) Preparation of Control A Control A was prepared by dissolving the following components in purified water to the concentrations indicated, and adjusting the pH to 9.5 (20°C). Sodium carbonate 21.20g / L (Kanto Chemical) Brij(R)-35 13.30g / L (Kishida Chemical)

[0037] (2) Preparation of Solution B-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution B-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) Ethanol 30mM (Fujifilm Wako Pure Chemical Industries) (3) Preparation of Solution B-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution B-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 30mM (Fujifilm Wako Pure Chemical Industries) (4) Preparation of Solution B-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution B-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) Glycerin 30mM (Fujifilm Wako Pure Chemical Industries)

[0038] (5) Preparation of Solution C-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution C-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Aminoethanol 30mM (Kanto Chemical) (6) Preparation of Solution C-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution C-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) DL-1-amino-2-propanol 30mM (Tokyo Chemical Industry Co., Ltd.) (7) Preparation of Solution C-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution C-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 30mM (Tokyo Chemical Industry Co., Ltd.) (8) Preparation of Solution C-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution C-4. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 3-Amino-1,2-propanediol 30mM (Fujifilm Wako Pure Chemical Industries)

[0039] (9) Preparation of Solution D-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution D-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 30mM (MP Bio) (10) Preparation of Solution D-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution D-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(Methylamino)ethanol 30mM (Tokyo Chemical Industry Co., Ltd.) (11) Preparation of Solution D-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution D-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) Diethanolamine 30mM (Kanto Chemical)

[0040] (12) Preparation of Solution E-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution E-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 30mM (Fujifilm Wako Pure Chemical Industries) (13) Preparation of Solution E-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution E-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) THEED 30mM (Fujifilm Wako Pure Chemical Industries) (14) Preparation of Solution E-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution E-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) EDTP 30mM (Fujifilm Wako Pure Chemical Industries) (15) Preparation of Solution E-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution E-4. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) EDTA 30mM (Sekisui Medical)

[0041] 2. Storage of the solution

[0042] Each of the solutions prepared in (1) to (15) above was stored in a light-shielded incubator at 30°C for 7 days.

[0043] 3. Measurement of oxidative condensation activity

[0044] The oxidative condensation capacity of the control was measured before and after carrying out step 2, and that of the other solutions was measured after carrying out step 2. If the oxidative condensation capacity of a solution is lower than that of the control, it can be said that the amines or alcohols contained in that solution have the effect of suppressing an increase in the oxidative condensation capacity. The values ​​are shown in Table 1. The oxidative condensation capacity was measured as follows. a. Preparation of oxidative condensation activity measurement reagent The following components were dissolved in pure water to the concentrations indicated, and the pH was adjusted to 7.35 (20°C) to prepare a reagent for measuring oxidative condensation activity. TES (Actec) 68.78g / L ADOS (Dojindo Chemical Research Institute) 0.53g / L 4-aminoantipyrine (Actec) 0.10g / L Peroxidase (Toyobo) 23kU / L b. Preparation of standard sample (100 μM hydrogen peroxide aqueous solution) A standard sample was prepared by dissolving hydrogen peroxide (30%) (Kanto Chemical) in pure water to a concentration of 100 μM. c.Measurement method Measurements were performed using a Canon Medical Systems TBA-120FR Sora Edition automated analyzer. 9 μL of the sample to be measured for oxidative condensation activity (measurement sample) was mixed with 200 μL of the oxidative condensation activity measurement reagent and incubated at 37°C for 10 minutes. The absorbance at 750 nm was subtracted from the absorbance at 546 nm to determine the absorbance. This value was proportionally calculated to the value obtained when a standard sample was used instead of the measurement sample, and the oxidative condensation activity of the measurement sample was calculated as a value (μM) when converted to the concentration of aqueous hydrogen peroxide solution.

[0045] [Table 1]

[0046] 4. Summary

[0047] The oxidative condensation activity of control A was 37 μM before storage and 84 μM after storage. The oxidative condensation activity of solutions B-1 to B-3, C-1 to C-4, D-1 to D-3, and E-1 to E-4 was lower than 84 μM after storage.

[0048] The oxidative condensation activity of control A, which did not contain amines or alcohols, was 37 μM before storage, but increased to 84 μM after storage. In contrast, the oxidative condensation activity of solutions B-1 to B-3, C-1 to C-4, D-1 to D-3, and E-1 to E-4, which contained amines or alcohols, remained below 84 μM even after storage, indicating that the inclusion of amines or alcohols suppressed the increase in oxidative condensation activity.

[0049] This confirmed that amines or alcohols have the effect of suppressing the increase in oxidative condensation ability.

[0050] [Example 2] (Confirmation of the effect of amines or alcohols in inhibiting an increase in oxidative condensation ability) The oxidative condensation ability was measured in a solution containing amines or alcohols, and the effect of amines or alcohols in suppressing an increase in the oxidative condensation ability was confirmed.

[0051] 1. Reagent Preparation

[0052] (16) Preparation of Control F The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare control F. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical)

[0053] (17) Preparation of Solution G-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution G-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 1000mM (Fujifilm Wako Pure Chemical Industries) (18) Preparation of Solution G-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution G-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 500mM (Fujifilm Wako Pure Chemical Industries) (19) Preparation of Solution G-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution G-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 50mM (Fujifilm Wako Pure Chemical Industries) (20) Preparation of Solution G-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution G-4. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 30mM (Fujifilm Wako Pure Chemical Industries) (21) Preparation of Solution G-5 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution G-5. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 10mM (Fujifilm Wako Pure Chemical Industries) (22) Preparation of Solution G-6 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution G-6. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 5mM (Fujifilm Wako Pure Chemical Industries)

[0054] (23) Preparation of Solution H-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution H-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 1000mM (Tokyo Chemical Industry Co., Ltd.) (24) Preparation of Solution H-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution H-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 500mM (Tokyo Chemical Industry Co., Ltd.) (25) Preparation of Solution H-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution H-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 50mM (Tokyo Chemical Industry Co., Ltd.) (26) Preparation of Solution H-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution H-4. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 30mM (Tokyo Chemical Industry Co., Ltd.) (27) Preparation of Solution H-5 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution H-5. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 10mM (Tokyo Chemical Industry Co., Ltd.) (28) Preparation of Solution H-6 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution H-6. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 5mM (Tokyo Chemical Industry Co., Ltd.) (29) Preparation of Solution H-7 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution H-7. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 1mM (Tokyo Chemical Industry Co., Ltd.) (30) Preparation of Solution H-8 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution H-8. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 0.1mM (Tokyo Chemical Industry Co., Ltd.)

[0055] (31) Preparation of Solution I-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 1000mM (MP Bio) (32) Preparation of Solution I-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 500mM (MP Bio) (33) Preparation of Solution I-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 50mM (MP Bio) (34) Preparation of Solution I-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-4. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 30mM (MP Bio) (35) Preparation of Solution I-5 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-5. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 10mM (MP Bio) (36) Preparation of Solution I-6 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-6. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 5mM (MP Bio) (37) Preparation of Solution I-7 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-7. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 1mM (MP Bio) (38) Preparation of Solution I-8 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-8. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 0.1mM (MP Bio) (39) Preparation of Solution I-9 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-9. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 0.01mM (MP Bio) (40) Preparation of Solution I-10 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-10. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 0.001mM (MP Bio) (41) Preparation of Solution I-11 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution I-11. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 0.0001mM (MP Bio) (42) Preparation of Solution I-12 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare solution I-12. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 0.00001mM (MP Bio)

[0056] (43) Preparation of Solution J-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-1. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 1000mM (Fujifilm Wako Pure Chemical Industries) (44) Preparation of Solution J-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-2. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 500mM (Fujifilm Wako Pure Chemical Industries) (45) Preparation of Solution J-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-3. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 50mM (Fujifilm Wako Pure Chemical Industries) (46) Preparation of Solution J-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-4. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 30mM (Fujifilm Wako Pure Chemical Industries) (47) Preparation of Solution J-5 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-5. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 10mM (Fujifilm Wako Pure Chemical Industries) (48) Preparation of Solution J-6 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-6. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 5mM (Fujifilm Wako Pure Chemical Industries) (49) Preparation of Solution J-7 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-7. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 1mM (Fujifilm Wako Pure Chemical Industries) (50) Preparation of Solution J-8 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-8. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 0.1mM (Fujifilm Wako Pure Chemical Industries) (51) Preparation of Solution J-9 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Solution J-9. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 0.01mM (Fujifilm Wako Pure Chemical Industries)

[0057] 2. Storage of the solution

[0058] Each of the solutions prepared in (16) to (51) above in 1 was stored in a light-shielded incubator at 30°C for 7 days.

[0059] 3. Measurement of oxidative condensation activity

[0060] The oxidative condensation capacity of the control was measured before and after carrying out step 2, and that of the other solutions was measured after carrying out step 2. If the oxidative condensation capacity of a solution is lower than that of the control, it can be said that the amines or alcohols contained in that solution have the effect of suppressing an increase in the oxidative condensation capacity. The values ​​are shown in Table 2. The oxidative condensation capacity was measured as follows. a. Preparation of oxidative condensation activity measurement reagent The following components were dissolved in pure water to the concentrations indicated, and the pH was adjusted to 7.35 (20°C) to prepare a reagent for measuring oxidative condensation activity. TES (Actec) 68.78g / L ADOS (Dojindo Chemical Research Institute) 0.53g / L 4-aminoantipyrine (Actec) 0.10g / L Peroxidase (Toyobo) 23kU / L b. Preparation of standard sample (100 μM hydrogen peroxide aqueous solution) A standard sample was prepared by dissolving hydrogen peroxide (30%) (Kanto Chemical) in pure water to a concentration of 100 μM. c.Measurement method Measurements were performed using a Canon Medical Systems TBA-120FR Sora Edition automated analyzer. 9 μL of the sample to be measured for oxidative condensation activity (measurement sample) was mixed with 200 μL of the oxidative condensation activity measurement reagent and incubated at 37°C for 10 minutes. The absorbance at 750 nm was subtracted from the absorbance at 546 nm to determine the absorbance. This value was proportionally calculated to the value obtained when a standard sample was used instead of the measurement sample, and the oxidative condensation activity of the measurement sample was calculated as a value (μM) when converted to the concentration of aqueous hydrogen peroxide solution.

[0061] [Table 2]

[0062] 4. Summary

[0063] The oxidative condensation activity of control F was 37 μM before storage and 84 μM after storage. The oxidative condensation activity of solutions G-1 to G-6, H-1 to H-8, I-1 to I-12, and J-1 to J-9 was lower than 84 μM after storage.

[0064] The oxidative condensation ability of the control solution F, which did not contain amines or alcohols, was 37 μM before storage, but increased to 84 μM after storage. In contrast, the oxidative condensation ability of solutions G-1 to G-6, H-1 to H-8, I-1 to I-12, and J-1 to J-9, which contained amines or alcohols, remained below 84 μM even after storage, indicating that the inclusion of amines or alcohols inhibited the increase in oxidative condensation ability.

[0065] This confirmed that amines or alcohols have the effect of suppressing the increase in oxidative condensation ability.

[0066] [Example 3] (Confirmation of measured values ​​in zinc measurement reagent) By examining the extent of the influence of hemoglobin on the measurement value of the substance to be measured in zinc measurement reagents containing amines or alcohols, we confirmed the effect of amines or alcohols in suppressing the increase in oxidative condensation ability.

[0067] 1. Reagent Preparation

[0068] (52) Preparation of Zinc Measurement Reagent First Reagent Control K The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare the control K of the first reagent for zinc measurement. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) (53) Preparation of Zinc Determination Reagent Daiichi Reagent Reagent L-1 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Reagent L-1, the first reagent for zinc measurement. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-Propanol 30mM (Fujifilm Wako Pure Chemical Industries) (54) Preparation of Zinc Determination Reagent Daiichi Reagent Reagent L-2 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Reagent L-2, the first reagent for zinc measurement. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) 2-(2-aminoethoxy)ethanol 30mM (Tokyo Chemical Industry Co., Ltd.) (55) Preparation of Zinc Determination Reagent Daiichi Reagent L-3 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Reagent L-3, the first reagent for zinc measurement. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) BTP 30mM (MP Bio) (56) Preparation of Zinc Determination Reagent Daiichi Reagent L-4 The following components were dissolved in purified water to the concentrations indicated, and the pH was adjusted to 9.5 (20°C) to prepare Reagent L-4, the first reagent for zinc measurement. Sodium carbonate 21.20g / L (Kanto Chemical) Brij-35 13.30g / L (Kishida Chemical) TIPA 30mM (Fujifilm Wako Pure Chemical Industries)

[0069] (57) Preparation of Zinc Determination Reagent Second Reagent The following components were dissolved in pure water to the concentrations shown below, and the pH was adjusted to 9.5 (20°C) to prepare a second reagent for measuring zinc. Sodium carbonate 21.20g / L (Kanto Chemical) 5-Br-PAPS 0.0696g / L (Actec)

[0070] 2. Storage of Reagents

[0071] The reagents prepared in (52) to (56) of 1 above were stored in a light-shielded incubator at 30°C for 7 days. (57) was stored in a light-shielded incubator at 5°C for 7 days.

[0072] 3. Check zinc concentration

[0073] The zinc concentration of the measurement sample was measured using each reagent before and after carrying out step 2. The zinc concentration after carrying out step 2 was divided by the zinc concentration before carrying out step 2, and the result was multiplied by 100 to obtain the rate of change (percent). The values ​​are shown in Table 3. The zinc concentration was measured as follows: a. Preparation of measurement samples According to the instructions for Interference Check A Plus (Sysmex), hemoglobin was added to pooled human serum to prepare a measurement sample with a hemoglobin concentration of 500 mg / dL. b. Zinc measurement method Measurements were performed using a Hitachi High-Tech 7180 automatic analyzer. 10 μL of the test sample was mixed with 150 μL of the first zinc test reagent (control K) and incubated at 37°C for 5 minutes. 50 μL of the second zinc test reagent was then added and incubated at 37°C for another 5 minutes. The difference in absorbance at the dominant wavelength of 546 nm and the subwavelength of 700 nm between 4 minutes 30 seconds after the addition of the first test reagent (point 16) and 5 minutes 8 seconds after the addition of the second test reagent (point 34) was proportionally calculated to the difference in absorbance measured when a 200 μg / dL zinc standard solution (Shinotest) was used instead of the test sample. Similar measurements were performed using reagents L-1 to L-4 instead of control K.

[0074] [Table 3]

[0075] 4. Summary

[0076] The change rate of the control K was 121%, but the change rates of the reagents L-1 to L-4 were lower than 121%.

[0077] The rate of change for the control K, which did not contain amines or alcohols, was 121%, while the rate of change for the reagents L-1 to L-4, which contained amines or alcohols, was lower than 121%. This indicates that the inclusion of amines or alcohols suppresses the increase in oxidative condensation activity, and therefore suppresses the change over time in the magnitude of the effect of hemoglobin on the measured values ​​of the substances to be measured.

[0078] This confirmed that amines or alcohols have the effect of suppressing the increase in oxidative condensation activity. The inclusion of amines or alcohols in a zinc measurement reagent had the effect of suppressing the change over time in the magnitude of the influence of hemoglobin on the measured value of the substance to be measured.

Claims

1. A biological sample measurement reagent characterized by containing amines or alcohols for the purpose of suppressing an increase in oxidative condensation ability.

2. The reagent according to claim 1, wherein the increase in oxidative condensation ability is due to a surfactant.

3. 3. The reagent according to claim 1, wherein the amine or alcohol is an alkanolamine.

4. The reagent according to claim 1 or 2, wherein the biological sample measurement reagent is a biochemical test reagent.

5. The reagent according to claim 3 , wherein the biological sample measurement reagent is a biochemical test reagent.

6. The reagent according to claim 4, wherein the biological sample measurement reagent is a zinc measurement reagent.

7. The reagent according to claim 5 , wherein the biological sample measurement reagent is a zinc measurement reagent.

8. A method for inhibiting an increase in oxidative condensation activity in a biological sample measurement reagent, the method comprising containing amines and / or alcohols.

9. The method according to claim 8, wherein the increase in oxidative condensation ability is due to the use of a surfactant.

10. 10. The method of claim 8 or 9, wherein the amines or alcohols are alkanolamines.

11. The method according to claim 8 or 9, wherein the biological sample measurement reagent is a biochemical test reagent.

12. The method according to claim 10, wherein the biological sample measurement reagent is a biochemical test reagent.

13. The method according to claim 11, wherein the biological sample measurement reagent is a zinc measurement reagent.

14. The method according to claim 12, wherein the biological sample measurement reagent is a zinc measurement reagent.

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