Stable determination kit for multi-parameter electrolyte analyzer

Abstract

The invention relates to a stable determination kit for a multi-parameter electrolyte analyzer. The stable determination kit comprises a solution A and a solution B, the solution A is prepared from the following components: 80 to 160 mmol / L of sodium chloride, 2 to 10 mmol / L of potassium chloride, 1 to 10 mmol / L of lithium acetate, 0.1 to 5 mmol / L of magnesium acetate, 0.1 to 4 mmol / L of anhydrous calcium chloride, 10 to 100 mmol / L of anhydrous sodium acetate, 50 to 100 mmol / L of buffer solution, 0.1 to 10 g / L of preservative, 0.1 to 10 g / L of stabilizer and 0.1 to 10 g / L of surfactant. The solution B is prepared from the following components: 10 to 100 mmol / L of sodium chloride, 2 to 10 mmol / L of potassium chloride, 1 to 10 mmol / L of lithium acetate, 0.1 to 5 mmol / L of magnesium acetate, 0.1 to 4 mmol / L of anhydrous calcium chloride, 10 to 100 mmol / L of anhydrous sodium acetate, 50 to 150 mmol / L of buffer solution, 0.1 to 10 g / L of preservative, 0.1 to 10 g / L of stabilizer and 0.1 to 10 g / L of surfactant. The content of K < + >, Na < + >, Cl <->, Ca < 2 + >, Li < + >, Mg < 2 + > and pH in a sample can be tested at the same time, the accuracy, repeatability and recovery rate are not affected when the sample is stored for 24 months at the temperature of 2-37 DEG C, and the raw materials are easy to obtain.

Description

Technical Field

[0001] This invention relates to reagents in the field of in vitro diagnostics, specifically to a stable assay kit for a multi-parameter electrolyte analyzer. Background Technology

[0002] Electrolytes are major components of human body fluids and participate in many important physiological and biochemical processes. The detection of ion concentrations plays a crucial role in the diagnosis of water and electrolyte metabolic disorders and acid-base imbalances, and is indispensable for monitoring the physical condition of certain critically ill patients. Hypernatremia can cause confusion, restlessness, convulsions, seizures, epileptic-like seizures, coma, and even death; hypokalemia can cause symptoms in the digestive, central nervous, circulatory, and urinary systems; hyperkalemia mainly manifests as bradycardia, premature ventricular contractions, atrioventricular block, ventricular fibrillation, and cardiac arrest.

[0003] Currently, the electrolyte analyzers and their accompanying reagents used in clinical practice do not include a comprehensive range of tests. Electrolyte analyzers containing lithium and magnesium channels are relatively rare, and the lack of these channels may lead to incomplete diagnosis. For example, magnesium ion concentration affects potassium and calcium metabolism; hyponatremia is a common cause of lithium ion poisoning, and hypokalemia increases the risk of lithium ion poisoning. Another example is testing only pH and not Cl... - While they can reflect acid-base imbalances, they cannot help pinpoint the underlying cause of the imbalance, such as respiratory acidosis caused by pneumonia or metabolic acidosis caused by diabetic ketoacidosis. Furthermore, these electrolyte analyzers have certain limitations regarding sample requirements; very few can measure electrolytes in urine, plasma, whole blood, or cerebrospinal fluid.

[0004] For reagents used in electrolyte analyzers, temperature changes can cause pH fluctuations in the buffer solution. Furthermore, the main components of electrolyte reagents are acid-base buffer solutions and inert inorganic salts, which are prone to microbial growth. This can lead to increased analyzer malfunctions and reduced electrode lifespan. Traditionally, formaldehyde is added to inhibit microbial growth. However, formaldehyde is hazardous. Therefore, current research focuses on developing reagents that do not contain formaldehyde or other volatile harmful substances. By screening suitable acid-base buffer solutions and adding appropriate preservatives and surfactants, the stability and shelf life of the reagents can be improved, while also ensuring electrode membrane stability and consistent measurement results.

[0005] Therefore, developing a stable, comprehensive multi-parameter electrolyte analyzer assay kit that meets clinical needs is of significant practical importance. Summary of the Invention

[0006] In summary, to overcome the shortcomings of the prior art, the technical problem to be solved by the present invention is to provide a stable assay kit for a multi-parameter electrolyte analyzer, which, while ensuring that the electrode membrane is not affected, provides a stable kit capable of simultaneously testing multiple parameters (K). + Na + Cl - Ca 2+ Li + Mg 2+ This multi-parameter electrolyte analyzer kit, which can test a wide range of sample types (serum, plasma, whole blood, urine, cerebrospinal fluid, pH), ensures that the ions do not interfere with each other and improves their stability by rationally selecting buffer systems, preservatives, stabilizers and various ions.

[0007] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a stable multi-parameter electrolyte analyzer assay kit, comprising solution A and solution B;

[0008] Liquid A comprises the following components:

[0009] Sodium chloride at a concentration of 80–160 mmol / L, potassium chloride at a concentration of 2–10 mmol / L, lithium acetate at a concentration of 1–10 mmol / L, magnesium acetate at a concentration of 0.1–5 mmol / L, anhydrous calcium chloride at a concentration of 0.1–4 mmol / L, anhydrous sodium acetate at a concentration of 10–100 mmol / L, buffer solution at a concentration of 50–100 mmol / L, preservative at a concentration of 0.1–10 g / L, stabilizer at a concentration of 0.1–10 g / L, and surfactant at a concentration of 0.1–10 g / L.

[0010] The above components were added to purified water and mixed to obtain solution A.

[0011] Liquid B comprises the following components:

[0012] Sodium chloride at concentrations of 10–100 mmol / L, potassium chloride at concentrations of 2–10 mmol / L, lithium acetate at concentrations of 1–10 mmol / L, magnesium acetate at concentrations of 0.1–5 mmol / L, anhydrous calcium chloride at concentrations of 0.1–4 mmol / L, anhydrous sodium acetate at concentrations of 10–100 mmol / L, buffer solution at concentrations of 50–150 mmol / L, preservative at concentrations of 0.1–10 g / L, stabilizer at concentrations of 0.1–10 g / L, and surfactant at concentrations of 0.1–10 g / L.

[0013] The above components were added to purified water and mixed to obtain solution B.

[0014] The kit contains multiple individual reagent bags, each containing one reagent. During testing, solution A and solution B are mainly used, while other reagent bags may contain cleaning solutions, etc.

[0015] Based on the above technical solution, the present invention can be further improved as follows:

[0016] Furthermore, the buffer solution is one or more of HEFES buffer, MES buffer, PBS buffer, and Tris-HCl buffer.

[0017] Furthermore, the buffer solution has a pH of 6.80–7.60 at 25°C.

[0018] Furthermore, the stabilizer is one or more of sorbitol, lactitol, sodium citrate, EDTA-Na2, and EGTA.

[0019] Furthermore, the surfactant is one or more of SB 3-10, Tween-20, Pluronic F-68, and dodecyl polyethylene glycol ether.

[0020] The beneficial effects of this invention are:

[0021] 1. The multi-parameter electrolyte analyzer assay kit of the present invention can simultaneously test K in samples. + Na + Cl - Ca 2+ Li + Mg 2+ It can measure pH content and, in addition to serum, can test plasma, whole blood, urine, and cerebrospinal fluid. It also exhibits good repeatability; added preservatives, stabilizers, and surfactants do not affect reagents, electrode membranes, or liquid path piping. It allows for long-term coexistence of six ions without precipitation or interference. Experiments show that accuracy, repeatability, and recovery remain unaffected when stored at 2–37°C for 24 months.

[0022] 2. Within the 24-month shelf life of this invention, K + Na + Cl - The repeatability CV values ​​for pH were both ≤1.0%, and for Ca... 2+ Li + Mg 2 + The intra-batch repeatability CV value is ≤2.0% for all samples.

[0023] 3. The reagent raw materials of the present invention are readily available, require no special preparation, and have low cost. Detailed Implementation

[0024] The principles and features of the present invention are described below with reference to specific examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0025] A stable assay kit for a multi-parameter electrolyte analyzer, comprising solution A and solution B;

[0026] Liquid A comprises the following components:

[0027] Sodium chloride at a concentration of 80–160 mmol / L, potassium chloride at a concentration of 2–10 mmol / L, lithium acetate at a concentration of 1–10 mmol / L, magnesium acetate at a concentration of 0.1–5 mmol / L, anhydrous calcium chloride at a concentration of 0.1–4 mmol / L, anhydrous sodium acetate at a concentration of 10–100 mmol / L, buffer solution at a concentration of 50–100 mmol / L, preservative at a concentration of 0.1–10 g / L, stabilizer at a concentration of 0.1–10 g / L, and surfactant at a concentration of 0.1–10 g / L.

[0028] Liquid B comprises the following components:

[0029] Sodium chloride at concentrations of 10–100 mmol / L, potassium chloride at concentrations of 2–10 mmol / L, lithium acetate at concentrations of 1–10 mmol / L, magnesium acetate at concentrations of 0.1–5 mmol / L, anhydrous calcium chloride at concentrations of 0.1–4 mmol / L, anhydrous sodium acetate at concentrations of 10–100 mmol / L, buffer solution at concentrations of 50–150 mmol / L, preservative at concentrations of 0.1–10 g / L, stabilizer at concentrations of 0.1–10 g / L, and surfactant at concentrations of 0.1–10 g / L.

[0030] The buffer solution is one or more of HEFES buffer, MES buffer, PBS buffer, and Tris-HCl buffer. Furthermore, the pH of the buffer solution is 6.80–7.60 at 25°C. The core function of the buffer solution is to maintain pH stability in the detection system, eliminating environmental interference for the specific response of the ion-selective electrode. The working mechanism of the buffer solution is designed around a precise match between pH buffering capacity and detection requirements. At 25°C, the buffer solution can strictly control the pH of the system within a suitable range of 6.80–7.60, which highly matches the optimal response environment of the ion-selective electrode membrane. When the sample is injected, reagents are switched (from solution A to solution B), or the ambient temperature fluctuates slightly, the buffer solution quickly offsets the acid-base changes in the system through its own proton transfer equilibrium, preventing pH fluctuations from causing changes in electrode membrane activity or abnormal target ion activity, thereby preventing deviations in potential difference detection. Meanwhile, the concentration of buffer solution B (50–150 mmol / L) is slightly higher than that of solution A (50–100 mmol / L), which can specifically optimize the system stability when detecting low-value ions, reduce the impact of small pH fluctuations on the potential difference under low ion concentrations, and help to accurately fit the complete linear calibration curve.

[0031] The stabilizer is one or more selected from sorbitol, lactitol, sodium citrate, EDTA-Na2, and EGTA. The stabilizer can achieve K... + Na+ Cl - Ca 2+ Li + Mg 2+ Long-term coexistence without precipitation ensures stable performance throughout the reagent's shelf life. The stabilizer primarily works by inhibiting ion precipitation and maintaining component activity, ensuring stable performance and repeatability of calibration / detection processes throughout the reagent's shelf life. It is suitable for the coexistence of six ions (K⁺, Na⁺, Cl⁻, Ca²⁺, Li⁺, Mg²⁺) in solutions A and B. The core working mechanism of the stabilizer consists of two points: First, through complexation and chelation effects, it forms stable complexes with metal ions (such as Ca²⁺ and Mg²⁺) in the system, preventing ion interactions from generating precipitation. This ensures that the concentrations of each ion in solutions A and B remain at the preset standard under storage conditions of 2–37℃, with no component loss. Second, it protects the active sites of the ion-selective electrode membrane, reducing the damage to the membrane structure caused by reagent components, while maintaining the consistency of electrode response and preventing calibration baseline drift due to reagent deterioration. This characteristic ensures the repeatability of results from high-value calibration with solution A, low-value calibration with solution B, and sample testing, making the CV values ​​of K⁺, Na⁺, Cl⁻, and pH ≤ 1.0%, and Ca⁻ ≤ 1.0%. 2+ The CV values ​​for Li⁺ and Mg²⁺ are ≤2.0%.

[0032] The surfactant is one or more of SB 3-10, Tween-20, Pluronic F-68, and dodecyl polyethylene glycol ether. The surfactant improves reagent compatibility without adversely affecting the electrode membrane or liquid path piping. By optimizing interfacial compatibility, the surfactant reduces liquid path adhesion and contact resistance, ensuring sufficient interaction between reagents, electrodes, and samples, and seamlessly connecting the entire calibration and detection process. The surfactant's working mechanism is reflected in interface regulation: on the one hand, the surfactant can reduce the surface tension of the reagent, increasing the contact area and compatibility between solution A, solution B, and the ion-selective electrode membrane, allowing the reagent to quickly and uniformly cover the electrode membrane surface, ensuring timely and sufficient response of the electrode to the target ion, and avoiding potential difference lag or numerical deviation due to insufficient contact; on the other hand, it can reduce the adhesion and residue of reagents and samples on the inner wall of the analyzer's liquid path piping, avoiding cross-contamination (such as solution A residue affecting solution B calibration, sample residue interfering with subsequent detection), while not corroding or damaging the electrode membrane or liquid path piping materials, ensuring long-term stable operation of the detection system and forming an efficient fit with the collaborative calibration process of solution A and solution B.

[0033] The beneficial effects of the present invention will be illustrated below through specific implementation.

[0034] Detection method: The electrolyte analyzer of Guilin Youlite Medical Electronics Co., Ltd. was used. The ion-selective electrode method was adopted. Each electrode with ion selectivity has a specific response to a specific ion. When the liquid to be tested passes through the electrode, the electrode film on the electrode and the liquid to be tested form a stable potential difference. The magnitude of the potential difference conforms to the Nernst equation. The concentration of the target ion in the liquid to be tested can be quantified by measuring the potential difference.

[0035] Example 1

[0036] A stable assay kit for a multi-parameter electrolyte analyzer, comprising solution A and solution B.

[0037] Liquid A comprises the following components:

[0038] Sodium chloride 85 mmol / L

[0039] Potassium chloride 4 mmol / L

[0040] Lithium acetate 1 mmol / L

[0041] Magnesium acetate 1 mmol / L

[0042] Anhydrous calcium chloride 2 mmol / L

[0043] Anhydrous sodium acetate 40 mmol / L

[0044] HEFES buffer 120 mmol / L

[0045] Gentamicin sulfate 0.1 g / L

[0046] Thiamphenicol 0.1 g / L

[0047] Sorbitol 5g / L

[0048] Sodium citrate 5g / L

[0049] Tween-20 1g / L

[0050] Liquid B comprises the following components:

[0051] Sodium chloride 55 mmol / L

[0052] Potassium chloride 8 mmol / L

[0053] Lithium acetate 2mmol / L

[0054] Magnesium acetate 2 mmol / L

[0055] Anhydrous calcium chloride 4 mmol / L

[0056] Anhydrous sodium acetate 40 mmol / L

[0057] HEFES buffer 100 mmol / L

[0058] Gentamicin sulfate 0.1 g / L

[0059] Thiamphenicol 0.1 g / L

[0060] Sorbitol 5g / L

[0061] Sodium citrate 5g / L

[0062] Tween-20 1g / L

[0063] Example 2

[0064] A stable assay kit for a multi-parameter electrolyte analyzer, comprising solution A and solution B.

[0065] Liquid A comprises the following components:

[0066] Sodium chloride 80 mmol / L

[0067] Potassium chloride 4 mmol / L

[0068] Lithium acetate 1.2 mmol / L

[0069] Magnesium acetate 1.2 mmol / L

[0070] Anhydrous calcium chloride 1.2 mmol / L

[0071] Anhydrous sodium acetate 30 mmol / L

[0072] Tris-HCl buffer 120 mmol / L

[0073] Gatifloxacin 0.1g / L

[0074] Thiamphenicol 0.1 g / L

[0075] lactitol 5g / L

[0076] Sodium citrate 5g / L

[0077] EDTA-Na2 1g / L

[0078] F-68 1g / L

[0079] Tween-20 1g / L

[0080] The B solution includes the following components:

[0081] Sodium chloride 50 mmol / L

[0082] Potassium chloride 8 mmol / L

[0083] Lithium acetate 2.5 mmol / L

[0084] Magnesium acetate 2.5 mmol / L

[0085] Anhydrous calcium chloride 2.5 mmol / L

[0086] Anhydrous sodium acetate 30 mmol / L

[0087] Tris-HCl buffer 80 mmol / L

[0088] Gatifloxacin 0.1g / L

[0089] Thiamphenicol 0.1 g / L

[0090] lactitol 5g / L

[0091] Sodium citrate 5g / L

[0092] EDTA-Na2 1g / L

[0093] F-68 1g / L

[0094] Tween-20 1g / L

[0095] Example 3

[0096] A stable assay kit for a multi-parameter electrolyte analyzer, comprising solution A and solution B.

[0097] Liquid A contains the following components:

[0098] Sodium chloride 100 mmol / L

[0099] Potassium chloride 4 mmol / L

[0100] Lithium acetate 2mmol / L

[0101] Magnesium acetate 2 mmol / L

[0102] Anhydrous calcium chloride 2 mmol / L

[0103] Anhydrous sodium acetate 30 mmol / L

[0104] PBS buffer 70 mmol / L

[0105] ProClin300 0.3g / L

[0106] Gentamicin sulfate 0.1 g / L

[0107] Sorbitol 3g / L

[0108] EGTA 1g / L

[0109] Tween-20 0.5g / L

[0110] Pluronic F-68 0.5g / L

[0111] The B solution includes the following components:

[0112] Sodium chloride 60 mmol / L

[0113] Potassium chloride 8 mmol / L

[0114] Lithium acetate 4 mmol / L

[0115] Magnesium acetate 4 mmol / L

[0116] Anhydrous calcium chloride 4 mmol / L

[0117] Anhydrous sodium acetate 40 mmol / L

[0118] PBS buffer 60 mmol / L

[0119] ProClin300 0.3g / L

[0120] Gentamicin sulfate 0.1 g / L

[0121] Sorbitol 3g / L

[0122] EGTA 1g / L

[0123] Tween-20 0.5g / L

[0124] Pluronic F-68 0.5g / L

[0125] Long-term calibration monitoring was conducted on Examples 1, 2, and 3 to test accuracy, repeatability, and recovery rate. The samples for accuracy testing were national standard lithium, sodium, potassium, magnesium, calcium, and chloride complex electrolyte frozen human serum and GBW(E)130342, with batch numbers 360018-202302 and 13010092307, respectively. The results are shown in Tables 1 to 3.

[0126] Table 1. Results of reagent kit accuracy test

[0127]

[0128]

[0129] The following conclusions can be drawn from Table 1: The reagent kit obtained by this invention has good stability and can be stored for 24 months at 2-40℃. All national standard products tested are qualified.

[0130] Table 2. Repeatability test results of the reagent kit

[0131]

[0132] The following conclusions can be drawn from Table 2: The reagent kit obtained by this invention has good reproducibility, and the CV value after being stored at 2-40℃ for 24 months is not significantly different from the CV value after 0 months.

[0133] Table 3. Reagent kit recovery test results

[0134]

[0135] The following conclusions can be drawn from Table 2: The kit obtained by the present invention can test serum, plasma, whole blood and urine, and the recovery rate is in the range of 90% to 110%.

[0136] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A stable multi-parameter electrolyte analyzer assay kit, characterized in that, Includes liquid A and liquid B; Liquid A comprises the following components: Sodium chloride at a concentration of 80–160 mmol / L, potassium chloride at a concentration of 2–10 mmol / L, lithium acetate at a concentration of 1–10 mmol / L, magnesium acetate at a concentration of 0.1–5 mmol / L, anhydrous calcium chloride at a concentration of 0.1–4 mmol / L, anhydrous sodium acetate at a concentration of 10–100 mmol / L, buffer solution at a concentration of 50–100 mmol / L, preservative at a concentration of 0.1–10 g / L, stabilizer at a concentration of 0.1–10 g / L, and surfactant at a concentration of 0.1–10 g / L. Liquid B comprises the following components: Sodium chloride at concentrations of 10–100 mmol / L, potassium chloride at concentrations of 2–10 mmol / L, lithium acetate at concentrations of 1–10 mmol / L, magnesium acetate at concentrations of 0.1–5 mmol / L, anhydrous calcium chloride at concentrations of 0.1–4 mmol / L, anhydrous sodium acetate at concentrations of 10–100 mmol / L, buffer solution at concentrations of 50–150 mmol / L, preservative at concentrations of 0.1–10 g / L, stabilizer at concentrations of 0.1–10 g / L, and surfactant at concentrations of 0.1–10 g / L.

2. The stable multi-parameter electrolyte analyzer assay kit according to claim 1, characterized in that, The buffer solution is one or more of HEFES buffer, MES buffer, PBS buffer, and Tris-HCl buffer.

3. The stable multi-parameter electrolyte analyzer assay kit according to claim 1, characterized in that, The buffer solution has a pH of 6.80–7.60 at 25°C.

4. The stable multi-parameter electrolyte analyzer assay kit according to claim 1, characterized in that, The stabilizer is one or more of sorbitol, lactitol, sodium citrate, EDTA-Na2, and EGTA.

5. The stable multi-parameter electrolyte analyzer assay kit according to any one of claims 1 to 4, characterized in that, The surfactant is one or more of SB 3-10, Tween-20, Pluronic F-68, and dodecyl polyethylene glycol ether.

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