Abstract: The invention concerns calibrators or calibration solutions which are based on a human serum matrix and which are used in a method for detecting cytokeratin, a process for producing them, a method for stabilizing cytokeratin and an immunological method for detecting cytokeratin in a sample.

Abstract: A novel reagent system for use with automated and semi-automated hematology analyzers including an essentially isotonic blood diluting reagent, a blood cell lysing and hemoglobin conversion reagent, and a second lysing reagent for differentiating white blood cells into classes by size and functional characteristics. The diluent reagent enhances properties for counting and sizing blood specimens, while stabilizing cellular volume and cellular integrity for many hours. The blood cell lysing reagent removes red blood cells and enables subsequent enumeration of white blood cells and simultaneous determination of hemoglobin without use of the toxic cyanide anion. The third lysing reagent and a companion quenching differentiates blood cells into classes by size and functional characteristics, based on d.c. impedance volume, conductivity/opacity and light scatter measurements. The companion quenching reagent adjusts pH and conductivity of the final measurement solution to match the analyzer system requirements.

Abstract: Methods of forming a density gradient by applying a centrifugal field to a solution of one or more metal ion chelate complexes are disclosed. The density gradients are self-forming equilibrium gradients and are useful for separating biological particles by ultracentrifugation. Also disclosed are methods of separating biological particles according to their density. Also disclosed are density gradients of lipoprotein particles and one or more metal ion chelate complexes, wherein the lipoprotein particles are partitioned along the density gradient according to their particle density.

Abstract: A lytic reagent composition for measuring nucleated blood cells in a blood sample is described. The lytic reagent composition contains a quaternary ammonium surfactant, an ethoxylated phenol, and an ethoxylated alcohol. When mixed with a blood sample, the lytic reagent composition lyses red blood cells and enables a differentiation of nucleated red blood cells from other cell types by DC impedance measurement. The lytic reagent composition can further contain an organic ligand for determining total hemoglobin concentration of a blood sample photometrically. Further disclosed is a lytic reagent system including the lytic reagent composition and a diluent. In addition, a single reagent composition containing salts is also disclosed, which can be used without a separate diluent. The lytic reagent compositions can be used for concurrent measurement of nucleated red blood cells, WBC, and hemoglobin of a blood sample.

Abstract: A method is provided for preparing preservative-free allergen test solutions in a prepared sterile environment. A sterile environment is prepared by utilizing a disinfectant wipe and a sterile barrier field. An antigen is added to a diluent to form a solution of the antigen by dispersing or suspending the antigen in the diluent. The solution is subjected to triple filtration under specific and sequential conditions to provide consistent and preservative-free allergen test solutions. Shelf life is extended by storing the solution at a temperature below 5° F. or by lyophilizing the allergen test solution.

Abstract: The present invention provides reagents for use in an automated environment for cell conditioning of biological samples wherein the cells or tissues are predisposed for access by reagent molecules for histochemical and cytochemical staining procedures. The reagents include components optimized to facilitate molecular access to cells and cell constituents within the biological sample. The present invention also provides reagents for use in an automated environment for removing or etching embedding media by exposing a biological sample to be stained in histochemical or cytochemical procedures without the dependence on organic solvents. The reagents include components optimized to facilitate removal or etching of the embedding media from the biological sample.

Abstract: The present invention is an additive preparation which contains an additive, an organic acid, a metal carbonate compound, and a surfactant agent which is capable of rendering the surface of a collection device to have properties that cause the surface to repel the adsorption of components of a body fluid sample. The preparation effervesces when in contact with a body fluid sample, thereby efficiently dispersing the additive and surfactant in a body fluid sample.

Abstract: A lytic reagent composition for measuring nucleated blood cells in a blood sample is described. The lytic reagent composition comprises a quaternary ammonium surfactant, an ethoxlyated phenol, and an ethoxylated alcohol. When mixed with a blood sample, the lytic reagent composition lyses red blood cells and enables a differentiation of nucleated red blood cells from other cell types by DC impedance measurement. The lytic reagent composition can further comprise an organic ligand for determining total hemoglobin concentration of a blood sample photometrically. Further disclosed is a lytic reagent system including the lytic reagent composition and a diluent. In addition, a single reagent composition containing salts is also disclosed, which can be used without a separate diluent. The lytic reagent compositions can be used for concurrent measurement of nucleated red blood cells, WBC, and hemoglobin of a blood sample.

Abstract: The invention provides a new single channel, single dilution method and system for identifying, analyzing and quantifying the cellular components of whole blood using a single channel, rather than multiple channels, of an automated hematology analyzer utilizing flow cytometry and the detection of the light scattered and absorbed by each cell. The single channel utilized in the method was previously known and used only for red blood cell and reticulocyte analysis. The method involves the use of an organic dye in the reagent solution for staining the nucleic acid of reticulocytes, including reticulated platelets, and white blood cells in the sample. The single channel method developed and described is particularly useful for determining white blood cell counts and assessing parameters of a whole blood sample, for blood samples from both human and non-human mammals.

Abstract: The control of the present invention involves a gentle chemical removal of red cells, leaving an intact white cell preparation. The preservation steps, namely the use of cross-linking agents as aldehydes, involve a step-wise process starting with very low concentrations of a cross-linking agent. The fixation part of the process outlined in this disclosure has also been applied to non-mammalian blood cells and therefor would appear to be a universal procedure for preparing all types of vertebrate blood cells.

Abstract: A method of quality control to diagnose the cause of a malfunction of an instrument. The method uses measurements of the physical property of a sample to diagnose the cause of a malfunction of an instrument. The spatial position of a control product sample is analyzed. Alternatively, the spatial position of a statistically significant number of patient blood samples can be used. The method enables the monitoring of an instrument for problems associated with debris and noise caused by red cell lysis inefficiency; instrument reagents pump volume settings; instrument laser alignments; instrument gain settings; and flow noise caused by partial plugs, residual plugs or other flow problems. The method provides a more specific indication of the type and cause of an instrument malfunctioning than non specific flagging provided by prior art methods.

Abstract: The present invention is drawn to an immunoassay capable of the rapid detection of a variety of test substances that may be present in a test sample. One feature of the invention is that extraction or isolation of the test substance occurs simultaneously with the formation of the primary antigen-test substance complex. The primary antigen-test substance complex is then captured in a solid phase format having a plurality of interstitial spaces which facilitate rapid and efficient detection. The immunoassay of the present invention works over a wide range of environmental conditions and is simple enough to be used in the absence of laboratory facilities.

Abstract: The present invention relates to methods for the production of a stable troponin preparation and its use as a calibrator and/or control in immunoassays. The formulation is prepared from mammalian, preferably bovine, heart tissue which provides a calibrator/control composition which remains stable over a long period of time.

Abstract: A homogeneous assay for determining the fumonisin content in grains uses the technique of fluorescence polarization. A grain extract is prepared by shaking a crushed grain sample with a solvent. A mixture is prepared by combining the grain extract with a tracer and with monoclonal antibodies specific to fumonisin. The tracer is able to bind to the monoclonal antibodies to produce a detectable change in fluorescence polarization. The tracer is prepared by conjugating fumonisin to a suitable fluorophore. The fluorescence polarization of the mixture is measured. The fumonisin concentration of the mixture may be calculated using a standard curve obtained by measuring the fluorescence polarization of a series of fumonisin solutions of known concentration.

Abstract: A method of analyzing nucleated red blood cells (NRBCs) in a blood sample and further enumerating NRBCs is disclosed. The method includes lysing a first aliquot and a second aliquot of a blood sample separately with a first lysing reagent system and a second lysing reagent system; measuring the first sample mixture in a flow cell by DC, RF, and light scatter measurements; measuring cell distributions and counting remaining blood cells in the second sample mixture by DC impedance measurements in a non-focused flow aperture; analyzing blood cell distribution patterns obtained from measuring the first sample mixture and from measuring the second sample mixture respectively; and further performing a combined analysis to differentiate NRBCs from other cell types and determine numbers of NRBCs in the blood sample.

Abstract: An aqueous tissue clearing solution for use in making biological tissues transparent is provided. The aqueous tissue clearing solution is selected from the group consisting of dimethyl sulfoxide, diatrizoate acid, ethylenediaminetetraacetic acid, glucamine, &bgr;-nicotinamide adenine dinucleotide phosphate, sodium diatrizoate, and derivatives of polyoxyalkalene. The aqueous tissue clearing solution is used to make tissue transparent for viewing through microscopy.

Abstract: The invention provides a bicarbonate-containing, crosslinker-free reagent composition which reverses and/or reduces sample handling effects, such as aeration-induced shrinkage and storage-induced swelling of cells in a whole blood sample, particularly for a blood sample requiring repeated sampling and/or subjected to long-term storage. The reagent composition serves as a diluent medium for a blood sample, or an aliquot or portion thereof. The pH of the reagent is in the range of about 7.2 to about 7.5, preferably 7.3. The stability of the pH 7.2-7.5 bicarbonate-containing reagent over time is maintained by storing the reagent in a flexible collapsible container which is impermeable to carbon dioxide and is comprised of a multilayered flexible material, preferably plastic, and attachable to a hematology analyzer.

Abstract: Agent for the removal of turbidity in biological samples comprising 0.5-10 mM Phenol, 0.5-15% polyoxyethylated triglyceride and at least one non-ionic ten-side in a range of 0.

Abstract: A method for differentiating and enumerating nucleated red blood cells in a blood sample is described. The method includes the steps of lysing red blood cells of a blood sample with a lytic reagent, measuring nucleated blood cells by DC impedance measurement in a non-focused flow aperture, differentiating nucleated red blood cells from other cell types, and reporting nucleated red blood cells in the blood sample. The method further includes subtracting nucleated red blood cells and other interference materials from the count of remaining blood cells, and reporting a corrected white blood cell count of the blood sample. Additionally, the method further includes measuring spectrophotometric absorbance of the sample mixture at a predetermined wavelength of a hemoglobin chromogen formed upon lysing the blood sample, and reporting hemoglobin concentration of the blood sample.

Abstract: An assembly device and method for collecting and testing fluid samples more specifically for preparing and stabilizing nucleic acid components in a closed system. The assembly comprises a sample collection container with preloaded testing reagents and a safety separator to contain the testing reagents during sample collection. A fluid sample is delivered to the container and the assembly is subjected to centrifugation whereby the centrifugal load causes the separator to deform so that the separator migrates through the test reagents mixing the sample and reagents, and comes to rest atop the solids at the bottom of the tube.

Abstract: Mixed-bed solid phases are provided, with methods for using such solid phases to isolate target nucleic acids, such as plasmid DNA, chromosomal DNA, RNA, or nucleic acids generated by enzymatic amplification from contaminants, including proteins, lipids, cellular debris, or other nucleic acids. The mixed-bed solid phases of this invention are mixtures of at least two different solid phases, each of which has a capacity to bind to the target nucleic acid under different solution conditions, and the capacity to release the nucleic acid under similar elution conditions. By exchanging solution conditions according to the methods of this invention, one can remove contaminants from the target nucleic acid bound to the mixed-bed solid phase, then elute the target nucleic acid in an elution buffer.

Abstract: A method of quality control to diagnose the cause of a malfunction of an instrument. The method uses measurements of the physical property of a sample to diagnose the cause of a malfunction of an instrument. The spatial position of a control product sample is analyzed. Alternatively, the spatial position of a statistically significant number of patient blood samples can be used. The method enables the monitoring of an instrument for problems associated with debris and noise caused by red cell lysis inefficiency; instrument reagents pump volume settings; instrument laser alignments; instrument gain settings; and flow noise caused by partial plugs, residual plugs or other flow problems. The method provides a more specific indication of the type and cause of an instrument malfunctioning than non specific flagging provided by prior art methods.

Abstract: Mixed-bed solid phases are provided, with methods for using such solid phases to isolate target nucleic acids, such as plasmid DNA, chromosomal DNA, RNA, or nucleic acids generated by enzymatic amplification from contaminants, including proteins, lipids, cellular debris, or other nucleic acids. The mixed-bed solid phases of this invention are mixtures of at least two different solid phases, each of which has a capacity to bind to the target nucleic acid under different solution conditions, and the capacity to release the nucleic acid under similar elution conditions. By exchanging solution conditions according to the methods of this invention, one can remove contaminants from the target nucleic acid bound to the mixed-bed solid phase, then elute the target nucleic acid in an elution buffer.

Abstract: The invention relates to a method and blood-withdrawal vessel for preparing blood samples for detecting homocysteine and/or total folate and is characterized in that the blood sample is brought into contact with (a) at least one reagent for lysis of the blood cells, (b) at least one inhibitor of the enzymes which produce and break down homocysteine, and optionally, (c) at least one acid.

Abstract: The invention relates to a method for the quick and direct on-site detection of drugs and drug substitutes which are in solid form. According to the invention, the drugs or drugs substitutes are transferred to a decomposition vessel or reaction vessel without being pretreated, especially without being reduced in size. Afterwards, they are mixed with a solvent or a solvent mixture containing at least one organic solvent. In addition, the suspension and/or solvent containing the drugs or drugs substitutes is/are directly subjected to a known drug test method, especially using drug test strips. The invention also provides a solvent or solvent mixture and a decomposition solution therefor, and a device for carrying out the method.

Abstract: The present invention relates to the use of sterol esters for the long-term stabilization of biological fluids, in particular even those which are obtained by lyophilization and subsequent reconstitution.

Abstract: This invention provides for a rapid and convenient method of simultaneous collection of both genomic and diagnostic information from a single sample on a bibulous pad by differential extraction of the diagnostic information from the genomic information. It is a surprising discovery of this invention that a PCR assay on the contents of the bibulous pad provides results comparable in reliability, specificity, and sensitivity to the best available serum (blood) based assays. The assays of this invention can be used to confirm each other, either by detecting the genomic information leading to the diagnostic information, or by detecting in the genomic information, a predisposition to a disease and confirming the presence of the disease through diagnostic testing.

Abstract: A self-contained signal generating device and methods for using and making the same are provided. The device and methods may detect the presence of a number of different substances, such as proteins, and utilizes a target material binding dye, which may precipitate a target material as well as stain it, and/or undergo a detectable change, e.g., an absorption or emission frequency shift, on binding of the substance to be detected.

Abstract: The present invention provides methods for diagnosing and/or monitoring thrombophilic disease in a patient that can result from the antiphospholipid antibody syndrome (aPL syndrome). The methods of the invention are premised on the inhibition of binding of an anticoagulant protein, annexin, preferably annexin-V, to phospholipids by antiphospholipid (aPL) antibodies in a patient blood sample.

Abstract: The application concerns oxidative metabolism in smooth muscle cells and to methods and materials related thereto. Provided is a method which is a medium suitable for the support of oxidative metabolism comprises: 1) incubating a cell or tissue sample with a specimen derived from a patient wherein the sample comprises smooth muscle cells; 2) measuring a marker of oxidative metabolism of the cell or tissue sample; and 3) detecting an increase in oxidative metabolism which is not attributable to a contractile demand for ATP, such as an increase in oxidative metabolism being indicative of the existence in a patient of an agent or combination of agents able to cause an increase in oxidative metabolism in smooth muscle cells.

Abstract: Mixed-bed solid phases are provided, with methods for using such solid phases to isolate target nucleic acids, such as plasmid DNA, chromosomal DNA, RNA, or nucleic acids generated by enzymatic amplification from contaminants, including proteins, lipids, cellular debris, or other nucleic acids. The mixed-bed solid phases of this invention are mixtures of at least two different solid phases, each of which has a capacity to bind to the target nucleic acid under different solution conditions, and the capacity to release the nucleic acid under similar elution conditions. By exchanging solution conditions according to the methods of this invention, one can remove contaminants from the target nucleic acid bound to the mixed-bed solid phase, then elute the target nucleic acid in an elution buffer.

Abstract: A rapid fluorescence staining method for facilitating flow cytometry analysis of reticulocytes is described. The method comprises contacting cells with a cocktail containing a detergent, sphering agent, and a cell impermeable dye, such as TO-PRO-3, for about one minute. Advantageously, the inventors have found that the cocktail permits the dye to penetrate the cell membrane rapidly.

Abstract: The present invention relates to stabilized compositions of troponin capable of serving as standard and/or control in immunoassays intended for assaying cardiac and/or skeletal troponin(s) in the blood serum or blood plasma of humans or animals. These stabilized compositions comprise, in aqueous solution, troponin I, troponin T and troponin C in the form of an I-T-C ternary complex.

Abstract: An improved apparatus and method for evaluating platelet functionality of a blood sample. The apparatus includes a plurality of test cells. Each of the cells includes a platelet function restoration agent, an anticoagulant agent, and a clotting reagent. At least one of the cells also includes a platelet activating agent. The clotting time is determined for each of the aliquot portions, and the relative clotting times of the aliquot portions in the cells are determinative of the platelet functionality of the sample. The method includes the steps of combining a platelet function restoration agent, an anticoagulant agent, a platelet activating agent, and the sample of blood to be tested to form a test mixture. The platelets of the sample are activated by adding a clotting reagent to the test mixture at the start of the activated clotting time test, and the activated clotting time test is terminated upon detecting a predetermined change in a property of the test mixture.

Abstract: A blood analyzing instrument includes a single transducer for simultaneously measuring the DC volume, RF conductivity, light scattering and fluorescence characteristics of blood cells passing through a cell-interrogation zone. Preferably, the transducer includes an electro-optical flow cell which defines a cell-interrogation zone having a square transverse cross-section measuring approximately 50×50 microns, and having a length, measured in the direction of cell flow, of approximately 65 microns.

Abstract: The present invention is an additive preparation for use in bodily fluid collection devices. The additive preparation has an additive, an organic acid and a metal carbonate compound. The preparation effervesces when in contact with a body fluid sample, thereby efficiently dispersing in a body fluid sample. The formulation is desirably tabulated to provide an effective, easily stored, and handled preparation. However, a binding or bulking agent may be added to the additive preparation formulation to provide binding and lubricating properties to the formulation. A binding agent enables granulating of the formulation without the forming of a pellet.

Abstract: Hematology control compositions and systems used to measure a plurality of parameters in a blood sample are provided. The hematology control compositions are particularly useful as a control for multi-parameter, automated instrument systems. The control compositions comprise a reticulocyte component, a white blood cell component, a red blood cell component, a nucleated red blood cell component, a platelet component and a reticulated platelet component. Methods of making and using the control compositions are also provided.

Abstract: This invention relates to lytic reagents and methods of using the lytic reagents for automatically determining leukocyte subpopulations in blood. More specifically, the new lytic reagents selectively lyse red blood cells and certain leukocyte subpopulations, which enables the differentiation of at least one subpopulation of leukocytes. The lytic reagents contain an ethoxylated long chain amine, a quaternary ammonium salt and an acid. When used in combination with a second lytic reagent system, one is able to obtain at least a five part differential of leukocytes by impedance and light scatter measurements, by impedance and radio frequency measurements, or by radio frequency and light scatter measurements.

Abstract: This invention relates to lytic reagents and methods of using the lytic reagents for automatically determining leukocyte subpopulations in blood. More specifically, the new lytic reagents selectively lyse red blood cells and certain leukocyte subpopulations, which enables the differentiation of at least one subpopulation of leukocytes. The lytic reagents contain a polyoxyethylene based surfactant, a quatemary ammonium salt and an acid. When used in combination with a second lytic reagent system, one is able to obtain at least a five part differential of leukocytes by impedance and light scatter measurements, by impedance and radio frequency measurements, or by radio frequency and light scatter measurements.

Abstract: Blood samples are stabilized for methemoglobin determination with a buffer composition containing (a) carbon monoxide-containing water; (b) sodium tetraborate or potassium tetraborate; and (c) KCN or NaCN. The buffer composition preferably may also have an erythrocytolysis agent. The buffer fixes the valence state of heme iron at a concentration representative of the blood at the time of collection, and maintains that fixed state for an extended period of time preventing further methemoglobin formation. The buffer also prevents reduction of existing target analyte, i.e., methemoglobin (ferric hemoglobin, Fe3+ hemoglobin) to normal reduced hemoglobin (ferrous hemoglobin, Fe2+ hemoglobin).

Abstract: The present invention relates to stable compositions useful as primary standards and calibrators and controls comprising a cardiac troponin I (cTnI) such as native, recombinant, addition and deletion forms thereof, whether or not complexed with other troponin subunits such as TnC and/or TnT, in an inactivated human serum. The compositions are obtained by incubating troponin complexes with human serum. The compositions are characterized by an immunodetectability ratio of epitopes on the N-terminal segment to epitopes on the C-terminal segment substantially equivalent to that of pooled, fresh serum from acute myocardial infarction patients.

Abstract: Hematology reference control cells and method of manufacture. The invention relates to the methods of preparing stable white blood cell (“WBC”) and nucleated red blood cell (“NRBC”) fractions and the hematology control reagents containing such stablized cells for primary use on a multi-angle light scatter based hematology instrument.

Abstract: A reagent for pH-metric acid number determination in a petroleum oil with low acid numbers (AN≦0.03 mg KOH/g oil) includes a salt of a strong base and a weak acid, and, an alkali in a mixture of water and an alcohol. The salt of a strong base and a weak is, preferably, sodium benzoate in a concentration of 0.02 to 0.1 M. The alcohol is, preferably, isopropanol in a concentration of from 50% to 80% by volume. The alkali is, preferably, an hydroxide and, most preferably, potassium hydroxide. The alkali should be adjusted to provide a pH′o, which is the pH of an equivalence-point on a titration curve of a strong acid added to a test portion of sodium benzoate, water and isopropanol.

Abstract: A composition and a method for using the composition for manipulating the electronic and optical properties of biological particles are disclosed. The composition generally has a hypotonic buffering solution, a polyhydroxy alcohol, a stabilizing agent, and, in some applications, a non-ionic surfactant. By varying the relative concentrations of these components and by adjusting the timing of their combination and interaction, the composition and method allow for the alteration of the electronic and optical properties of the particles to achieve target values for the properties. In one particularly advantageous application, the composition and method of the invention allow for the creation of selected analogs for the subpopulations of human leukocytes from a single biological particle for use as a control product in differentiating particle analyzers.

Abstract: The lysis of erythrocytes is accomplished by subjecting whole blood treated with an anticoagulant at a pH between 4 and 9 with a nitrogenous heterocyclic compound, most preferably pyrrolidine chloride.

Abstract: The invention provides a very fast and reliable method and reagent composition for determining reticulocyte and erythrocyte counts, identification and characterization, as well as platelet counts, in a whole blood sample using fully automated hematology analyzers. The reagent composition includes a zwitterionic surfactant as sphering agent for reticulocytes and erythrocytes, an organic cationic dye, e.g., Oxazine 750, for staining the reticulocytes, and buffer solution components for maintaining a reagent pH of about 7.2 to 7.8, and an osmolarity of about 292.+-.5. On the basis of the particular pH, ionic strength, and dye concentration, the reagent composition of the present method improves upon previous methods, thus allowing fully automated blood sample analyses to be completed in less than about 30 seconds, with only about a 20 second incubation of sample in the reagent solution before analysis.

Abstract: A reagent composition and method is provided for identification of reticulated cells from other cell types in a blood cell sample by using optical measurement. More particularly, the reagent composition contains a nucleic acid dye and sphering agent. More particularly, the method enables the identification of reticulated platelets and reticulated erythrocytes. In addition, the method provides for a concurrent determination of cell by cell hemoglobin of the reticulated erythrocytes and mature erythrocytes in the blood cell sample.

Abstract: Methods for detecting granulocytes and for providing an at least semiquantitative indication of granulocyte level and kits for implementing those methods. A blood sample is drawn, and components that might interfere with the assay are removed and/or neutralized. Granulocytes present in the sample are then disrupted to release intracellular myeloperoxidase, and the sample is contacted with a peroxide and a chromogenic donor dye. The myeloperoxidase enzyme catalyzes hydrogen peroxide-involved reactions which result in the dye changing color if, and to the extent that, granulocytes are present in the blood sample.

Abstract: A reagent for classification and counting of leukocytes, the reagent containing at least one dye which has the following structural formula ##STR1## where R.sub.1 is a hydrogen atom or an alkyl group, R.sub.2 and R.sub.3 each represent a hydrogen atom, a lower alkyl group or a lower alkoxy group, R.sub.4 represents a hydrogen atom, an acyl group or an alkyl group, Z represents a sulfur atom, an oxygen atom, or a carbon atom having a lower alkyl group, n denotes 0, 1 or 2, and X.sup.- represents an anion,and specifically binds to RNA to increase in fluorescence intensity, and a method for classification and counting of leukocytes which uses the reagent, whereby abnormal cells such as immature leukocytes and abnormal leukocytes can be classified and counted easily and highly accurately, and at the same time, classification and counting of normal leukocytes as well as the counting of leukocytes can be performed.

Abstract: A reagent for measurement of leukocytes and hemoglobin concentration in the blood includes a cationic surfactant in an amount sufficient to lyse erythrocytes and denature hemoglobin, at least one of the following hemoglobin stabilizers: (a) sulfosalicylic acid, or its salt, in an amount effective for promoting the conversion of hemoglobin into methemoglobin, (b) 0.2 to 10.0 g/L of a water-soluble chelating agent having a nitrogen atom and a carboxyl group, and (c) piperazine, or its salt, in an amount effective for promoting the conversion of hemoglobin into methemoglobin, and a buffer for maintaining pH at 4 to 6.