Standard substance development test method and system based on solution preparation

Abstract

The invention belongs to the technical field of standard substance development, discloses a standard substance development test method and system based on solution preparation, and aims to improve the precision: through a high-precision automatic solution preparation device and calibration equipment, manual operation errors are avoided, and the precision of standard substance preparation is improved. Operation is simplified, manual operation steps are reduced in the automatic liquid preparation process, the operation process is simplified, and the error rate is reduced. Uniformity and stability are guaranteed, uniformity and stability of the standard substance in the preparation, storage and use processes are guaranteed through uniformity inspection and stability monitoring, and reliability is improved. By means of automatic equipment and an optimized preparation process, the preparation efficiency of the standard substance is improved, and time and labor are saved. And quality is ensured: a strict quality control and traceability system ensures the quality consistency and traceability of each batch of standard substances, and the overall quality management level is improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of reference material development, and particularly relates to a test method and system for reference material development based on solution preparation. Background Art

[0002] The existing chemical titration method is widely used in the preparation of reference materials, but it faces a series of problems of accuracy and stability in practical applications. First of all, low accuracy is one of the prominent disadvantages of the chemical titration method. During the titration process, the judgment of the titration end point usually depends on the visual observation of the experimenter. This kind of human judgment is prone to subjective differences, resulting in inaccurate concentration control, and then affecting the concentration of the prepared reference material. This deficiency makes it difficult for the chemical titration method to obtain ideal results in occasions with high-precision requirements.

[0003] The operational complexity is also a major problem of the chemical titration method. The titration process usually requires multiple operations and calculations, including a series of steps such as liquid addition, solution stirring, end point judgment, and result recording. Such operations are cumbersome and prone to errors due to human negligence. It not only prolongs the experimental time but also increases the error sources, making it difficult for the chemical titration method to meet the requirements of rapid and large-scale reference material preparation.

[0004] In addition, the instability during the titration process also brings uncertainty to the experimental results. Some chemical reagents show the characteristic of a narrow titration jump range near the titration end point. This characteristic makes the end point judgment more difficult, and it is easy to miss or overdose the titrant, thus causing a concentration deviation. Especially in the environment of precision analysis and high-precision requirements, this instability will directly affect the reliability of the prepared reference material.

[0005] Different from the chemical titration method, the gravimetric preparation mainly relies on weighing, but it also faces limitations. During the gravimetric preparation process, the weighing accuracy highly depends on the experimental environment and equipment. Factors such as temperature, humidity, vibration, and static electricity in the environment will affect the weighing accuracy. In addition, the weighing steps in the preparation process need to be repeated many times, which is time-consuming and has a large operation difficulty. It has high requirements for the skills of the operators and increases the difficulty of preparation.

[0006] The problem of incomplete dissolution also limits the application scope of the gravimetric preparation. Some substances are difficult to completely dissolve in the solution. Even if the weighing is accurate, it may lead to uneven concentration of the reference material during the preparation process, thus affecting the accuracy of the results. For easily crystallized or poorly soluble compounds, this problem is more obvious, making the gravimetric preparation inconvenient in practical applications.

[0007] In summary, the inaccuracies, operational complexities, and environmental sensitivities of existing chemical titration and gravimetric methods in the preparation of reference materials limit their applications. In many experimental scenarios that require high precision, rapidity, and large-scale preparation, the existing methods are difficult to fully meet the requirements, and there is an urgent need for a more simple, efficient, and stable method for preparing reference materials. Summary of the Invention

[0008] In view of the problems existing in the prior art, the present invention provides a test method for developing reference materials based on solution preparation.

[0009] The present invention is implemented as follows. A test method for developing reference materials based on solution preparation includes:

[0010] Step 1: Precise Preparation

[0011] Use an automatic liquid dispensing device controlled by a computer for liquid dispensing, with an accuracy of up to ±0.01 mL;

[0012] Automatically perform liquid dispensing through computer control;

[0013] Select high-purity solvents and reagents;

[0014] Use calibrated or verified containers and equipment, such as: the error of a volumetric flask does not exceed ±0.05 mL;

[0015] Step 2: Homogeneity Test

[0016] Use a magnetic stirrer or an ultrasonic oscillator for mixing. The rotation speed of the magnetic stirrer is controlled at 500 - 1000 rpm, and the power of the ultrasonic oscillator is set at 50 - 100 W;

[0017] After preparation, filter the solution through a filter with a pore size of 0.22 μm or 0.45 μm to remove fine particles;

[0018] Conduct a homogeneity test on the characteristic values of the reference material to ensure the uniformity of the reference material solution.

[0019] Step 3: Stability Monitoring

[0020] Conduct long-term stability monitoring, and set different storage conditions, such as 4°C, 25°C, and 40°C;

[0021] At regular time intervals, perform detections at certain intervals to monitor the changes in the characteristic values of the reference material. Use equipment such as high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) for detections;

[0022] Use containers with good sealing and low dissolution rates, such as glass ampoules or polytetrafluoroethylene (PTFE) bottles, to store the reference material, and the containers need to pass an airtightness test;

[0023] Step 4: Certification of Reference Materials

[0024] The certified value of the reference material is determined by using a reference method or by collaborative certification among multiple laboratories, and the uncertainty is evaluated simultaneously;

[0025] Step 5: Quality Control

[0026] During the preparation of each batch, quality control and inspection are carried out, including purity inspection of starting materials, real-time monitoring of the preparation process, and purity inspection of the final product;

[0027] A detailed record and traceability system is established to record the operating steps, reagents, and equipment used in each preparation, and it is managed using a laboratory information management system;

[0028] The reference materials prepared in each batch need to pass consistency verification, and the verification results should comply with relevant standards and certification standards.

[0029] Furthermore, the precise preparation method:

[0030] (1) Liquid preparation is carried out using a computer-controlled automatic liquid dispensing device:

[0031] Equipment selection: Select a high-precision automatic liquid dispensing device, including an electronic titrator or a fully automatic liquid dispenser;

[0032] Computer control: Control the liquid dispensing device through computer software and set the preparation parameters, including the target concentration and volume;

[0033] Calibration and verification: Regularly calibrate the liquid dispensing device and verify it using reference materials;

[0034] (2) Use high-purity reagents, including solutes and solvents:

[0035] Solute selection: Select high-purity guaranteed reagent grade reagents, with a purity generally above 99.9%, to reduce the influence of impurities on the reference material;

[0036] Solvent selection: Use refined solvents, including ultrapure water, absolute ethanol, methanol, etc., to ensure that as few impurities as possible are introduced by the solvent itself;

[0037] (3) Use calibrated or verified containers and equipment:

[0038] Container selection: Select high-precision volumetric flasks, measuring cylinders, pipettes, and pipettors to ensure the volume accuracy of the containers themselves;

[0039] Measurement assurance: Regularly verify or calibrate volumetric flasks, graduated cylinders, pipettes, and pipettors, and use reference materials or standard solutions to verify or calibrate the instruments and equipment for testing; The verification or calibration situation should be recorded in detail.

[0040] Furthermore, the method for homogeneity testing:

[0041] Use a magnetic stirrer or ultrasonic oscillator for mixing:

[0042] Equipment selection: Select a suitable magnetic stirrer or ultrasonic oscillator;

[0043] Stirring time: Set a reasonable stirring time according to the properties of the solution, usually between 10 - 30 minutes, to ensure complete dissolution of the solute;

[0044] Filter after mixing is completed:

[0045] Filter selection: Filter the solution using a microporous membrane with a pore size of 0.22 μm or 0.45 μm to remove existing fine particles;

[0046] Operation steps: Slowly filter the prepared solution through the filter;

[0047] Conduct homogeneity testing on the characteristic values of the reference material to ensure the uniformity of the reference material solution.

[0048] Furthermore, the stability monitoring method:

[0049] Conduct long - term stability monitoring:

[0050] Test conditions: Select different storage conditions, including different temperatures, humidities, and light - shielding environments;

[0051] Test cycle: At regular time intervals, conduct tests at certain intervals, lasting for 6 months or longer, and observe the changes in the characteristic values of the reference material;

[0052] Storage in containers used:

[0053] Container selection: Select glass bottles, ampoules, or plastic bottles with good sealing performance;

[0054] Storage environment: Store in a dry, cool, and light - shielding environment.

[0055] Furthermore, the value - determination method:

[0056] Selection of the value determination method: Select an appropriate method, such as a reference method (e.g., constant current precision coulometry, isotope dilution mass spectrometry), or a method of collaborative value determination by multiple laboratories, etc., to determine the characteristic values of the reference material. At the same time, consider the uncertainty components introduced by the operations in the entire preparation process, and scientifically and reasonably evaluate the uncertainty. Finally, determine the range and magnitude of the characteristic values of the reference material;

[0057] Furthermore, the quality control method:

[0058] Strict quality control and detection:

[0059] Detection method: Use high-precision analytical instruments, including high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS), etc., to detect the characteristic values of the prepared reference material;

[0060] Detection items: Detect the characteristic values of the reference material, such as concentration, purity, impurity content, etc., to ensure compliance;

[0061] Establish a detailed record and traceability system.

[0062] Furthermore, the establishment of the detailed record and traceability system:

[0063] Record content: Detail the operation steps of each preparation, the reagents and equipment used, the preparation parameters, and the detection results;

[0064] Traceability system: Establish an electronic traceability system for easy query and management.

[0065] Another object of the present invention is to provide a reference material development test system based on solution preparation, including:

[0066] Precise preparation module: Use a computer-controlled automatic liquid dispensing device to perform liquid dispensing, and automatically perform liquid dispensing through computer control; Use high-purity solvents and reagents; Use calibrated or verified containers and equipment;

[0067] Homogeneity inspection module: Use a magnetic stirrer or ultrasonic oscillator for mixing; After mixing, filter the solution through a filter to remove fine particles; Perform homogeneity inspection on the characteristic values of the reference material to ensure the uniformity of the reference material solution.

[0068] Stability monitoring module: Conduct long-term stability monitoring, and monitor the stability of the reference material under different storage conditions; Use containers with good sealing and low dissolution rate to store the reference material; Perform stability monitoring on the characteristic values of the reference material to ensure the stability of the reference material.

[0069] Value determination module: Select appropriate methods, such as reference methods (e.g., constant current precision coulometry, isotope dilution mass spectrometry), or methods such as collaborative value determination by multiple laboratories, to determine the characteristic values of reference materials, and at the same time evaluate the uncertainty;

[0070] Quality control module, conduct quality control and detection during the preparation process of each batch; establish a detailed record and traceability system to record the operation steps, reagents and equipment used in each preparation.

[0071] Combined with the above technical solutions and the technical problems solved, please analyze the advantages and positive effects of the technical solution to be protected by the present invention from the following aspects:

[0072] First, the present invention improves the preparation accuracy: Through high-precision automatic liquid dispensing devices and calibration equipment, human operation errors are avoided, and the accuracy of the preparation of reference material solutions is improved.

[0073] Simplify the operation: The automated liquid dispensing process reduces the number of human operation steps, simplifies the operation process, and reduces the error rate.

[0074] Ensure uniformity and stability: Through uniformity inspection and stability monitoring, ensure the uniformity and stability of reference materials during preparation, storage and use, and improve the reliability of quality.

[0075] Improve efficiency: Automated equipment and optimized preparation processes improve the preparation efficiency of reference materials, saving time and labor.

[0076] Ensure quality: Strict quality control and traceability systems ensure the quality consistency and traceability of each batch of reference materials, improving the overall quality management level.

[0077] Second, the technical solution of the present invention solves the technical problems in the prior art through the following aspects and has made remarkable technical progress:

[0078] 1) Precise preparation:

[0079] Problems in the prior art: Traditional manual liquid dispensing methods are easily affected by human operation errors and environmental factors, resulting in low preparation accuracy.

[0080] Technical progress: The present invention uses high-precision automatic liquid dispensing devices and computer control to ensure that the accuracy of liquid dispensing reaches ±0.01 mL. At the same time, high-purity reagents and calibrated or verified containers are used, significantly improving the accuracy and consistency of the preparation of reference materials.

[0081] 2) Uniformity inspection:

[0082] Problems in the prior art: Traditional mixing methods are time-consuming and laborious, resulting in uneven solutions and affecting the quality of reference materials.

[0083] Technological progress: The present invention uses a magnetic stirrer or an ultrasonic oscillator for mixing and filters the solution through a 0.22-micron or 0.45-micron filter to ensure the uniformity and purity of the solution, eliminating the influence of tiny particles on the reference material.

[0084] Use equipment such as high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) to detect the characteristic values of the reference material, ensuring that the uniformity during the preparation process of the reference material meets the requirements.

[0085] 3) Stability monitoring:

[0086] Problems in the prior art: There is a lack of systematic long-term stability monitoring, and the stability of the reference material under different storage conditions cannot be guaranteed.

[0087] Technological progress: The present invention sets different storage conditions, conducts stability monitoring regularly, and uses equipment such as high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) to detect the characteristic values of the reference material, ensuring the stable properties of the reference material during long-term storage. At the same time, to avoid changes in the characteristic values of the reference material caused by solvent evaporation, containers with good sealing and low dissolution rate are used to store the reference material, effectively preventing the influence of the external environment on it.

[0088] 4) Quality control:

[0089] Problems in the prior art: The quality control means in the traditional preparation process are insufficient, and it is difficult to ensure the consistency of the quality of each batch of reference materials.

[0090] Technological progress: In the preparation process of each batch, the present invention conducts comprehensive quality control and detection, records detailed operation steps, reagents and equipment used, and uses a laboratory information management system (LIMS) for management and traceability. At the same time, each batch of reference materials passes the consistency test to ensure that it meets relevant standards, such as ISO 17034 or NIST certification standards.

[0091] Remarkable technological progress:

[0092] 1) Improve the precision of reference material preparation: Through a high-precision automatic liquid dispensing device and computer control, the preparation process is made more precise and stable.

[0093] 2) Ensure the uniformity and purity of the solution: Use a magnetic stirrer, an ultrasonic oscillator and a filter to ensure the uniformity and purity of the solution, eliminate the influence of particles on the reference material, and test the uniformity of the reference material.

[0094] 3) Long-term stability monitoring: Through systematic stability monitoring and the use of containers with good sealing and low dissolution rate, ensure the long-term stability of reference materials under different storage conditions.

[0095] 4) Comprehensive quality control: Establish a detailed record and traceability system throughout the preparation process, conduct comprehensive quality control and monitoring to ensure the consistency of the quality of each batch of reference materials.

[0096] Generally speaking, the present invention has made significant technological progress in the preparation, homogeneity inspection, stability monitoring and quality control of reference materials, solved the key problems in the prior art, and improved the reliability and accuracy of reference materials prepared based on solutions. Description of the Drawings

[0097] Figure 1 It is a flow chart of the method for developing reference materials prepared based on solutions provided by an embodiment of the present invention.

[0098] Figure 2 It is a flow chart of the precise preparation method provided by an embodiment of the present invention.

[0099] Figure 3 It is a block diagram of the structure of the system for developing reference materials prepared based on solutions provided by an embodiment of the present invention. Detailed Embodiments

[0100] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0101] As Figure 1 shown, a method for developing reference materials prepared based on solutions provided by an embodiment of the present invention includes the following steps:

[0102] S101, Precise preparation:

[0103] Use an automatic liquid dispensing device controlled by a computer to dispense liquid, and automatically dispense liquid through computer control;

[0104] Adopt high-purity reagents, including solutes and solvents;

[0105] Use calibrated or verified containers and equipment;

[0106] S102, Homogeneity inspection:

[0107] Use a magnetic stirrer or an ultrasonic oscillator to mix; after mixing, filter the solution through a filter to remove fine particles; conduct a homogeneity inspection on the reference material to ensure that its homogeneity meets the relevant requirements;

[0108] S103, Stability Monitoring:

[0109] Conduct long-term stability monitoring, monitor the stability of reference materials under different storage conditions to ensure that their stability meets relevant requirements; store reference materials using containers with good sealing and low dissolution rate;

[0110] S104: Assignment of Reference Materials:

[0111] Assign the characteristic values of reference materials using primary methods or the collaborative assignment method of multiple laboratories, and simultaneously evaluate the uncertainty;

[0112] S105, Quality Control:

[0113] During the preparation process of each batch, conduct quality control and monitoring;

[0114] Establish a detailed record and traceability system to record the operation steps, reagents, and equipment used in each preparation.

[0115] As Figure 2 shown, the precise preparation method provided by the embodiment of the present invention:

[0116] S201, Conduct liquid preparation using a computer-controlled automatic liquid dispensing device:

[0117] Equipment selection: Select a high-precision automatic liquid dispensing device, including an electronic titrator or a fully automatic liquid dispenser;

[0118] Computer control: Control the liquid dispensing device through computer software and set the preparation parameters, including the target concentration, volume, etc.;

[0119] Calibration and verification: Regularly calibrate the liquid dispensing device and verify it irregularly using reference materials;

[0120] S202, Use high-purity reagents, including solutes and solvents:

[0121] Solute selection: Select high-purity guaranteed reagent grade reagents, with a purity generally above 99.9%, to reduce the influence of impurities on reference materials;

[0122] Solvent selection: Use refined solvents, including ultrapure water, absolute ethanol, methanol, etc., to ensure the minimum influence of the solvent itself;

[0123] S203, Use calibrated or verified containers and equipment:

[0124] Container selection: Select high-precision volumetric flasks, pipettes, pipettors, and graduated cylinders, and calibrate or verify them to ensure the accuracy of the volume of the containers themselves;

[0125] Calibration method: Regularly calibrate or verify the testing instruments and equipment using reference materials or standard solutions; the calibration or verification situation should be recorded in detail.

[0126] The homogeneity inspection method provided by the embodiments of the present invention:

[0127] Use a magnetic stirrer or an ultrasonic oscillator for mixing:

[0128] Equipment selection: Select a suitable magnetic stirrer or ultrasonic oscillator;

[0129] Stirring time: Set a reasonable stirring time according to the properties of the solution, usually between 10 - 30 minutes, to ensure that the solute is completely dissolved and uniformly mixed;

[0130] Filter after preparation:

[0131] Filter selection: Filter the solution using a 0.22 - micron or 0.45 - micron microporous membrane to remove existing fine particles;

[0132] Operation steps: Slowly filter the mixed solution through the filter;

[0133] Use equipment such as high - performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP - MS) to detect the characteristic values of the reference material, ensuring that the homogeneity of the reference material preparation process meets the requirements.

[0134] The stability monitoring method provided by the embodiments of the present invention:

[0135] Conduct long - term stability monitoring:

[0136] Test conditions: Select different storage conditions, including different temperatures, humidities, and light - shielding environments;

[0137] Test cycle: At regular time intervals, conduct detections at certain intervals for 6 months or longer, observe the changes in the characteristic values of the reference material, and evaluate its stability;

[0138] Container selection: Select glass bottles, ampoules, or plastic bottles with good sealing performance and low dissolution rate as containers for storage;

[0139] Storage environment: The prepared reference material is stored in a dry, cool, and light - shielding environment.

[0140] The quality control method provided by the embodiments of the present invention:

[0141] Strict quality control and detection:

[0142] Detection method: Use high-precision analytical instruments, including high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS), etc. to detect the characteristic values of the prepared reference materials;

[0143] Detection items: Detect the characteristic values of the reference materials, including concentration, purity, impurity content, etc., to ensure compliance;

[0144] Establish a detailed record and traceability system.

[0145] The detailed record and traceability system provided by the embodiment of the present invention:

[0146] Record content: Record in detail the operation steps of each preparation, the reagents and detection equipment used, the preparation parameters, the detection results, etc.;

[0147] Traceability system: Establish an electronic traceability system for easy query and management.

[0148] As Figure 3 shown, a reference material development test system based on solution preparation provided by the embodiment of the present invention includes:

[0149] Precise preparation module: Use a computer-controlled automatic liquid dispensing device to perform liquid dispensing, and automatically perform liquid dispensing through computer control; Use high-purity reagents; Use calibrated or calibrated containers and equipment;

[0150] Homogeneity inspection module: Use a magnetic stirrer or an ultrasonic oscillator to mix. After mixing, filter the solution through a filter to remove fine particles. Use high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS), etc. to detect the characteristic values of the prepared reference materials to ensure that its homogeneity meets the requirements;

[0151] Stability monitoring module: Monitor the stability of the reference materials under different storage conditions; Use high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS), etc. to detect the characteristic values of the prepared reference materials for long-term stability monitoring. Use containers with good sealing and low dissolution rate to store the reference materials to ensure that its stability meets the requirements;

[0152] Certification Module: Select appropriate methods, such as reference methods (e.g., constant-current precision coulometry, isotope dilution mass spectrometry), or collaborative certification among multiple laboratories, etc., to certify the characteristic values of reference materials, and at the same time evaluate the uncertainty; the implementation process of the certification module mainly includes four steps: method selection, experimental operation, data analysis, and uncertainty evaluation. First of all, in the certification process, method selection is one of the key steps. According to the characteristics and application requirements of the reference material, select a suitable certification method. Such as common reference methods, including constant-current precision coulometry, which determines the concentration of the target component in the solution by controlling the current constant and accurately measuring the charge quantity; or isotope dilution mass spectrometry, which selects a stable isotope with a low natural abundance of the measured element as a diluent for trace and ultra-trace target detection. In addition, collaborative certification among multiple laboratories can also be used for certification. By comprehensively analyzing the measurement results of the same reference material by multiple laboratories, systematic errors can be reduced, and the reliability and accuracy of the certification can be improved. Next, the experimental operation needs to be carried out under strictly controlled experimental conditions to ensure the accuracy of the certification process. When using constant-current precision coulometry, the operator needs to ensure the stability and accuracy of the current, and carry out the reaction in a high-purity solvent to avoid interference of impurities on the results. During the experiment, all equipment and instruments used need to be strictly calibrated and verified to ensure the accuracy of the equipment. At the same time, during the collaborative certification among multiple laboratories, each laboratory needs to use the same operating procedures and equipment to ensure the comparability of the results.

[0153] Data analysis is another important step in the certification module. After the experiment is completed, the collected raw data will be processed through strict statistical analysis. For constant-current precision coulometry, the measured data will be used to calculate the characteristic values of the reference material through calculation, and corrected in combination with the experimental conditions and reaction efficiency. For collaborative certification among multiple laboratories, the measurement results of all participating laboratories will be summarized, and the final characteristic values will be obtained through mathematical statistics analysis, and the discreteness and deviation of the results of each laboratory will be determined, so as to ensure the accuracy of the characteristic values.

[0154] Finally, uncertainty evaluation is one of the key links in the certification module. According to the error sources generated in each link of the experimental process, comprehensively consider factors such as instrument precision, operation error, and environmental conditions, and calculate the uncertainty of the certification result. For constant-current precision coulometry, the uncertainty evaluation needs to consider factors such as the accuracy of current measurement, electrolyte purity, and reaction efficiency. In collaborative certification among multiple laboratories, the uncertainty evaluation needs to comprehensively consider the measurement errors, human factors, method differences and other influencing factors of each laboratory. Through detailed uncertainty evaluation, the credibility of the certification result will be fully guaranteed, and the reliability of the reference material in practical applications will be ensured.

[0155] A quality control module is used to conduct quality control and detection during the preparation process of each batch; a detailed record and traceability system is established to record the operation steps, reagents, and equipment used in each preparation.

[0156] The standard substance preparation test system based on solution preparation consists of multiple modules to ensure the high precision and stability of the standard substance. First, the precise preparation module automatically and precisely prepares the solution under computer control through a high-precision automatic liquid dispensing device. This module uses high-purity reagents to ensure the purity and accuracy of chemical substances during the preparation process. In addition, all containers and equipment are strictly verified and calibrated to ensure precision and consistency during the preparation process.

[0157] Next, the homogeneity inspection module is responsible for ensuring the homogeneity of the standard substance during the preparation process. During the preparation process, the solution is fully mixed by a magnetic stirrer or an ultrasonic oscillator to eliminate any concentration gradient. Then, the solution is filtered through a filter to remove existing fine particles to ensure the homogeneity and purity of the final standard substance, and the homogeneity of the characteristic values of the standard substance is inspected to ensure the uniformity of the standard substance solution.

[0158] After the standard substance is prepared, the stability monitoring module conducts long-term stability monitoring on it. This module continuously monitors the stability of the standard substance under different storage conditions to ensure its stability during the storage period. The standard substance is stored in a dry, cool, and dark environment and stored in containers with good sealing and low dissolution rate, which can effectively prevent the influence of external factors on the standard substance, thus ensuring its chemical stability.

[0159] Finally, the value determination module and the quality control module jointly ensure the accuracy and reliability of the standard substance. The value determination module selects appropriate value determination methods, such as the constant current precision coulometry or the collaborative value determination method of multiple laboratories, etc., to precisely determine the characteristic values of the standard substance and evaluate the uncertainty. The quality control module conducts strict quality control and detection during the preparation process of each batch, and establishes a detailed record and traceability system to record the operation steps, reagents, and equipment used in each preparation, ensuring the quality and traceability of the standard substance. Through these steps, the system can reliably develop standard substances with high precision, homogeneity, and stability meeting the requirements.

[0160] Specific implementation of the present invention:

[0161] Technical solution: A standard substance preparation test method based on solution preparation

[0162] 1. Precise preparation:

[0163] Use an automatic liquid dispensing device controlled by a computer to dispense liquid:

[0164] Equipment selection: Select a high-precision automatic liquid dispensing device, including an electronic titrator or a fully automatic liquid dispenser;

[0165] Computer control: Control the liquid dispensing device through computer software and set the preparation parameters, including the target concentration and volume;

[0166] Calibration and verification: Regularly calibrate the liquid dispensing device and verify it using reference materials;

[0167] Use high-purity reagents, including solutes and solvents:

[0168] Solute selection: Select high-purity guaranteed reagent grade reagents, with a purity generally above 99.9%, to reduce the impact of impurities on the reference materials;

[0169] Solvent selection: Use refined solvents, including ultrapure water, absolute ethanol, methanol, etc., to ensure the minimum impact of the solvent itself;

[0170] Use calibrated or verified containers and equipment:

[0171] Container selection: Select high-precision volumetric flasks, pipettes, pipettors, and measuring cylinders, and calibrate or verify them to ensure the accuracy of the volume of the containers themselves;

[0172] Calibration method: Regularly calibrate or verify the testing instruments and equipment using reference materials or standard solutions; The calibration or verification situation should be recorded in detail;

[0173] 2. Homogeneity test:

[0174] Use a magnetic stirrer or an ultrasonic oscillator for mixing:

[0175] Equipment selection: Select a suitable magnetic stirrer or ultrasonic oscillator;

[0176] Stirring time: Set a reasonable stirring time according to the properties of the solution, usually between 10 - 30 minutes, to ensure complete dissolution of the solute;

[0177] Filter after preparation:

[0178] Filter selection: Filter the solution using a 0.22 μm or 0.45 μm microporous membrane to remove existing fine particles;

[0179] Operation steps: Slowly filter the mixed solution through the filter;

[0180] Use equipment such as high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) to conduct homogeneity tests on the reference materials to ensure compliance with the relevant homogeneity requirements;

[0181] 3. Stability monitoring:

[0182] Conduct long-term stability monitoring:

[0183] Test conditions: Select different storage conditions, including different temperatures, humidities, and light-proof environments;

[0184] Test cycle: Conduct detections at certain time intervals, every once in a while, for 6 months or longer, observe the changes in the characteristic values of the reference material, and evaluate its stability;

[0185] Store using containers with good sealing and low dissolution rate:

[0186] Container selection: Select glass bottles, ampoules, or plastic bottles with good sealing and low dissolution rate;

[0187] Storage environment: The prepared reference material is stored in a dry, cool, and light-proof environment.

[0188] Detection method: Use high-precision analytical instruments, including high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS), etc. to detect the characteristic values of the prepared reference material;

[0189] Conduct long-term stability monitoring, continuously monitor the stability of the reference material under different storage conditions to ensure it meets the stability-related requirements;

[0190] Detection items: Detect the characteristic values of the reference material, including concentration, purity, and impurity content, to ensure compliance;

[0191] Store the reference material using containers with good sealing and low dissolution rate;

[0192] 4. Quality control:

[0193] During the preparation process of each batch, conduct strict quality control and detection to ensure the consistency and accuracy of each batch of reference material.

[0194] Establish a detailed record and traceability system to record the operation steps, reagents, and equipment used in each preparation.

[0195] Record content: Detail the operation steps, reagents, detection equipment, preparation parameters, detection results, etc. for each preparation;

[0196] Traceability system: Establish an electronic traceability system for easy query and management.

[0197] Test method for the development of reference material based on solution preparation

[0198] 1. Precise preparation

[0199] 1.1 Use a computer-controlled automatic liquid dispensing device for liquid preparation

[0200] Equipment selection: Select a high-precision automatic liquid dispensing device, such as an electronic titrator or a fully automatic liquid dispenser, with an accuracy of up to ±0.01 mL or higher.

[0201] Computer control: Control the liquid dispensing device through computer software, and set preparation parameters such as target concentration, volume, etc., to ensure the accuracy during the automated preparation process.

[0202] Calibration and verification: Regularly calibrate the liquid dispensing device and verify it using reference materials to ensure the accuracy and stability of the equipment.

[0203] 1.2 Use high-purity solvents and reagents

[0204] Reagent selection: Select high-purity guaranteed reagent grade reagents, with a purity generally above 99.9%, to reduce the influence of impurities on the reference materials.

[0205] Solvent selection: Use refined solvents such as ultrapure water, absolute ethanol, methanol, etc., to ensure the minimum influence of impurities introduced by the solvents themselves.

[0206] 1.3 Use calibrated or verified containers and equipment

[0207] Container selection: Select containers such as high-precision volumetric flasks, pipettes, pipettors, and measuring cylinders to ensure the lowest influence of the volume accuracy of the containers themselves.

[0208] Calibration method: Regularly verify or calibrate the containers to ensure their accuracy. There should be verification or calibration reports or records.

[0209] 2. Homogeneity test

[0210] 2.1 Use a magnetic stirrer or an ultrasonic oscillator for mixing

[0211] Equipment selection: Select a suitable magnetic stirrer or ultrasonic oscillator for mixing to ensure the mixing uniformity and stability.

[0212] Stirring time: Set a reasonable stirring time according to the properties of the solution, usually between 10 - 30 minutes, to ensure complete dissolution of the solute.

[0213] 2.2 Filter after preparation

[0214] Filter selection: Use a microporous membrane with a pore size of 0.22 μm or 0.45 μm to filter the solution and remove existing fine particles.

[0215] Operation steps: Slowly pass the prepared solution through the filter to avoid the influence of fine particles.

[0216] 2.3 Detection

[0217] Use equipment to conduct homogeneity inspection on reference materials to ensure compliance with relevant homogeneity requirements;

[0218] 3. Stability Monitoring

[0219] 3.1 Conduct long-term stability monitoring

[0220] Test conditions: Select different storage conditions, such as different temperatures, humidities, light-proof environments, etc., to conduct long-term stability monitoring.

[0221] Test cycle: At regular time intervals, conduct detections at certain intervals, detect the characteristic values of reference materials stored under different conditions, continue for 6 months or longer, observe the changes in the characteristic values of reference materials to ensure stability.

[0222] 3.2 Store using containers with good sealing and low dissolution rate

[0223] Container selection: Select glass bottles or plastic bottles with good sealing and low dissolution rate to avoid contact between the solution and air or contamination caused by precipitation from the container.

[0224] Storage environment: Store in a dry, cool and light-proof environment to reduce the influence of the external environment on reference materials.

[0225] 4. Quality Control

[0226] 4.1 Strict quality control and detection

[0227] Detection method: Use high-precision analytical instruments, such as high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS) and other equipment, to detect the characteristic values of the prepared reference materials.

[0228] Detection items: Detect the concentration, purity, impurity content, etc. of reference materials to ensure compliance with requirements.

[0229] 4.2 Establish a detailed record and traceability system

[0230] Record content: Detail the operating steps of each preparation, the reagents and equipment used, preparation parameters, detection results, etc.

[0231] Traceability system: Establish an electronic traceability system for easy query and management to ensure the traceability of each batch of reference materials.

[0232] By adopting a high-precision automatic liquid dispensing device and calibration equipment, the present invention significantly improves the precision of standard substance preparation. Traditional chemical titration and gravimetric methods have human judgment errors, while the automatic liquid dispensing device can achieve precise dosage control and automated preparation, thus eliminating human errors in operation. Through precise calibration of the liquid dispensing equipment, the errors in the preparation process are strictly controlled within the minimum range, ensuring the accurate concentration of each batch of standard substances and effectively improving the precision.

[0233] In terms of operation, the automated liquid dispensing process greatly simplifies the operation flow and reduces the necessity of manual intervention. Traditional preparation methods have cumbersome steps and are easily affected by human errors. The present invention integrates complex operation steps into the system through an automated process, thereby reducing the number of manual operation steps and the possibility of errors, making the entire preparation process more convenient and stable. In addition, the automated control also provides an operator-friendly interface, significantly reducing the professional skill requirements and being suitable for large-scale popularization and application.

[0234] To ensure the quality reliability of standard substances during preparation, storage, and use, the present invention also introduces a homogeneity inspection and stability monitoring mechanism. The homogeneity inspection ensures that the measured values of standard substances in each packaging unit are within the characteristic values and their uncertainty ranges, ensuring the consistency of preparation. The stability monitoring ensures that the characteristic values and uncertainties of standard substances meet the expected requirements through timely detection during storage and use. Thus, the reliability of standard substances is fully guaranteed, enabling them to meet the requirements of high-precision experiments.

[0235] The present invention also significantly improves the preparation efficiency of standard substances. Through automated equipment and optimized process design, the entire preparation process no longer relies entirely on manual operation and can achieve continuous and efficient preparation, significantly shortening the preparation cycle. On the premise of ensuring precision, homogeneity, and stability, the automated production of standard substances not only saves time but also reduces the input of human resources, enabling laboratories and enterprises to quickly respond to the demand for standard substances.

[0236] To ensure the overall quality, the present invention is also equipped with a strict quality control and traceability system. The system records the preparation process, key parameters, and quality inspection data of each batch of standard substances to ensure the consistency and traceability of each batch of products. This full-process quality control system fundamentally improves the management level of standard substances, enabling the products to pass multiple quality inspections before entering the market or scientific research processes, providing a high-quality foundation for subsequent experiments.

[0237] Generally speaking, through the technical solution of the present invention, the problems existing in the prior art, such as insufficient precision, cumbersome operation, and poor stability, are solved, and the precision, stability, and reliability of the preparation of reference materials are greatly improved. The refined automated preparation process, reliable quality assurance system, strict quality control, and traceability management together constitute a set of efficient and sustainable reference material preparation solutions, which not only meet the stringent requirements of scientific research but also lay a solid foundation for quality control in practical applications.

[0238] The above is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention shall be covered by the protection scope of the present invention.

Claims

1. A test method for developing reference materials based on solution preparation, characterized in that, Including the following steps: Step 1: Precise preparation Use a computer-controlled automatic liquid dispensing device for liquid dispensing, with an accuracy of up to ±0.01 mL; Carry out liquid dispensing through a computer-controlled automatic liquid dispensing device; Select solvents and reagents with high purity, with a purity of not less than 99.9%; Use calibrated or verified containers and equipment, with the error of volumetric flasks not exceeding ±0.05 mL; Step 2: Homogeneity test Use a magnetic stirrer or ultrasonic oscillator for mixing. The rotation speed of the magnetic stirrer is controlled at 500 - 1000 rpm, and the power of the ultrasonic oscillator is set at 50 - 100 W; After the preparation is completed, filter the solution through a filter with a pore size of 0.22 μm or 0.45 μm to remove fine particles; Use equipment such as high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) to conduct homogeneity tests on reference materials to ensure that they meet the relevant requirements for homogeneity; Step 3: Stability monitoring Conduct long-term stability monitoring, setting different storage conditions, such as 4°C, 25°C, and 40°C; At regular time intervals, conduct tests at certain intervals to monitor the change of characteristic values of reference materials to ensure that they meet the relevant requirements for stability. Use equipment such as high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) for testing; Use containers with good sealing and low dissolution rate, such as glass bottles, ampoules, or polytetrafluoroethylene (PTFE) bottles to store reference materials, and the containers need to pass the airtightness test; Step 4: Certification of reference materials Use the primary method or the way of collaborative certification by multiple laboratories to certify reference materials, and at the same time conduct the evaluation of uncertainty; Step 5: Quality control During the preparation process of each batch, conduct quality control and testing, including the purity detection of starting materials, real-time monitoring of the preparation process, and the detection of the concentration or purity of the final product, etc.; Establish a detailed record and traceability system, record the operation steps, reagents, and equipment used in each preparation, and manage them using a laboratory information management system; The reference materials prepared in each batch need to pass the consistency verification, and the verification results should meet the relevant standards and certification criteria.

2. The test method for developing reference materials based on solution preparation according to claim 1, characterized in that The said precise preparation method: (1) Use a computer-controlled automatic liquid dispensing device for liquid dispensing: Equipment selection: Select a high-precision automatic liquid dispensing device, including an electronic titrator or a full-automatic liquid dispenser; Computer control: Control the liquid dispensing device through computer software, and set the preparation parameters, including the target concentration, volume, etc.; Calibration and verification: Regularly calibrate the liquid dispensing device and verify it using reference materials; (2) Use reagents with high purity: Reagent selection: Select high-purity guaranteed reagent grade reagents, including solutes and solvents; Solvent selection: Use refined solvents, including ultrapure water, absolute ethanol, methanol, etc., to ensure that the solvent itself does not introduce impurities; (3) Use calibrated or verified containers and equipment: Container selection: Select high-precision volumetric flasks, pipettes, pipettors, and measuring cylinders to ensure the volume accuracy of the containers themselves; Calibration method: Regularly use reference materials or standard solutions to calibrate or verify the testing instruments and equipment; the calibration or verification situation should be recorded in detail.

3. The test method for developing reference materials based on solution preparation according to claim 1, wherein The said homogeneity test method: Mix using a magnetic stirrer or an ultrasonic oscillator: Equipment selection: Select a suitable magnetic stirrer or ultrasonic oscillator; Stirring time: Set a reasonable stirring time according to the properties of the solution, usually between 10 - 30 minutes, to ensure complete dissolution of the solute; Filter after preparation: Filter selection: Filter the solution using a 0.22 - micron or 0.45 - micron microporous membrane to remove existing fine particles; Operation steps: Slowly filter the prepared solution through the filter; Use equipment to conduct homogeneity inspection on the reference material to ensure it meets the relevant requirements for homogeneity.

4. The test method for developing reference materials based on solution preparation according to claim 1, wherein The stability monitoring method: Conduct long - term stability monitoring: Test conditions: Select different storage conditions, including different temperatures, humidities, and light - proof environments; Test cycle: Conduct tests at regular time intervals, at certain intervals of time, for 6 months or longer, and observe the changes in the characteristic values of the reference material; Store using containers with good sealing and low dissolution rate: Container selection: Select glass bottles, ampoules, or plastic bottles with good sealing; Storage environment: Store in a dry, cool, and light - proof environment.

5. The test method for developing reference materials based on solution preparation according to claim 1, characterized in that, The value - assignment method: Use the reference method or the method of collaborative value - assignment by multiple laboratories to assign the characteristic values of the reference material, and at the same time conduct the evaluation of uncertainty.

6. The test method for developing reference materials based on solution preparation according to claim 1, characterized in that, The quality control method: Strict quality control and detection: Detection method: Use high - precision analytical instruments, including high - performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP - MS), etc. to detect the prepared reference material; Detection items: Detect the concentration, purity, impurity content, etc. of the reference material to ensure compliance; Establish a detailed record and traceability system.

7. The test method for developing reference materials based on solution preparation according to claim 5, characterized in that, The establishment of a detailed record and traceability system: Record content: Detail the operation steps of each preparation, the reagents and equipment used, the preparation parameters, and the detection results; Traceability system: Establish an electronic traceability system for easy query and management.

8. An experimental system for developing reference materials based on solution preparation as described in any one of claims 1-6, characterized in that, Include: Precise preparation module, used to perform liquid preparation using a computer - controlled automatic liquid dispenser, automatically perform liquid preparation through computer control; use high - purity solvents and reagents; use calibrated or verified containers and equipment; Homogeneity inspection module, used to ensure the homogeneity of the reference material during the preparation process; mix using a magnetic stirrer or an ultrasonic oscillator, and after mixing, filter the solution through a filter to remove fine particles, and conduct homogeneity inspection on the characteristic values of the reference material to ensure the uniformity of the reference material solution; Stability monitoring module, used to conduct long - term stability monitoring and monitor the stability of the reference material under different storage conditions; Store the reference material using containers with good sealing and low dissolution rate; Value - assignment module: Use the reference method or the method of collaborative value - assignment by multiple laboratories to assign the characteristic values of the reference material, and at the same time conduct the evaluation of uncertainty; Quality control module, used to conduct quality control and detection during the preparation of each batch; establish a detailed record and traceability system, and record the operation steps, reagents, and equipment used in each preparation.

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