Analytical method for measuring dissolution amount of HMDI (hexamethylene diisocyanate) in medical instrument containing polyurethane material

Abstract

The invention belongs to the technical field of analytical chemistry, and discloses an analysis method for determining the dissolution amount of HMDI in a medical instrument containing a polyurethane material, and the method comprises the following specific steps: 1, preparing a solution, namely preparing a mobile phase, a diluent, a derivatization reagent, a derivative solvent, a standard stock solution, a series of standard curve solutions, a process blank solution and an accuracy solution; the specific analysis method for the dissolution amount of the HMDI in the medical instrument containing the polyurethane material is established, the blank in the prior art is filled, the problem that the HMDI residue detection in the medical instrument industry lacks a unified standard is solved, and a reliable technical means is provided for product safety evaluation; meanwhile, 9-(methylaminomethyl) anthracene is adopted as a derivatization reagent and can be subjected to a specific reaction with the HMDI to generate a stable fluorescent derivative, and a fluorescent detector is combined for detection, so that the sensitivity of the method is remarkably improved, and the detection requirement of the dissolution amount of the low-concentration HMDI can be met.

Description

Technical Field

[0001] This invention belongs to the field of analytical chemistry technology, specifically an analytical method for determining the amount of HMDI leaching in medical devices containing polyurethane materials. Background Technology

[0002] Leachable materials in medical devices refer to chemical substances released by medical devices in contact with the human body during clinical use under the influence of media such as water and body fluids. These include process residues, material monomers, and degradation products. These leachable materials may pose short-term or long-term safety hazards to the human body. Therefore, establishing accurate detection methods for their quantitative analysis is an important part of medical device safety assessment.

[0003] Polyurethane materials are widely used in the manufacture of medical devices such as implantable drug delivery devices and catheters due to their good biocompatibility, elasticity, and corrosion resistance. HMDI is a commonly used monomer in the synthesis of polyurethane materials. It is a saturated cyclohexane derivative of MDI and has high light stability and weather resistance. However, HMDI may cause adverse reactions such as respiratory irritation and skin allergies. Its residual dissolution in medical devices is directly related to the safety of product use. Currently, there are industry standards for the testing of MDI, but there is no unified standard for the detection method of HMDI residual dissolution. This makes it impossible for medical device manufacturers to effectively assess the potential risks of HMDI residues in their products to the human body. Therefore, it is urgent to develop an accurate and reliable method for detecting HMDI dissolution. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides an analytical method for determining the amount of HMDI leaching in medical devices containing polyurethane materials, thereby solving the problems mentioned in the background section.

[0005] To achieve the above objectives, the present invention provides the following technical solution: an analytical method for determining the HMDI dissolution amount in medical devices containing polyurethane materials, the specific steps of which are as follows: Step 1: Solution Preparation Prepare mobile phase, diluent, derivatization reagent, derivative solvent, standard stock solution, series of standard curve solutions, process blank solution and accuracy solution; Step 2: Sample Pretreatment Take a medical device sample containing polyurethane material, remove the outer packaging and non-human contact components, cut it into pieces and weigh about 0.1g of the sample, add the extraction solvent and derivatization reagent, seal and protect from light and sonicate for 30min. Step 3: Concentration and Reconstitution Take 10.00 ml of the solution after the reaction in step two, blow it dry with nitrogen using a nitrogen blower, add the derivative solvent and dissolve it by sonication, then filter it through a 0.22 μm filter membrane to obtain the test solution; Step 4: Instrument Testing The test solution was analyzed by ultra-high performance liquid chromatography-fluorescence detection, gradient elution was performed according to a specific elution program, and the peak area of ​​HMDI was recorded. Step 5: Quantitative Calculation A standard curve is plotted with the peak area of ​​the standard curve solution as the ordinate and the concentration as the abscissa, and a linear equation is obtained. The peak area of ​​the test solution is then substituted into the equation to calculate the measured value of HMDI solution.

[0006] Preferably, the method for preparing the solution in step one is as follows: Mobile phase A: Weigh 1.54177 g of ammonium acetate into a 1 L volumetric flask, add water to dissolve and make up to volume, adjust the pH to 4.08 with acetic acid, and sonicate for 15 min; Mobile phase B: Measure 1000 ml of acetonitrile and sonicate at room temperature for 15 min; Diluent: dichloromethane; Derivatization reagent: Weigh 26.18 mg of 9-(methylaminomethyl)anthracene into a 100 ml volumetric flask, add dichloromethane to the mark, and shake well; Derivative solvent: Measure 50 ml of N,N-dimethylformamide into a 100 ml volumetric flask, add 40 ml of acetonitrile, and dilute to the mark with purified water. Shake well. Standard stock solution: Weigh 15.135 mg HMDI standard into a 10 ml volumetric flask, dilute to volume with dichloromethane, and shake well; Secondary stock solution of standard: Transfer 166.0 μl of primary stock solution into a 5 ml volumetric flask, dilute to volume with dichloromethane, and shake well; Standard curve solutions: Take appropriate amounts of the secondary stock solution of the standard, dilute with diluent to prepare linear solutions with concentrations of 0.309 μg / ml, 0.602 μg / ml, 1.003 μg / ml, 1.504 μg / ml, and 2.006 μg / ml. Take 1.000 ml of each linear solution, mix with 1.000 ml of derivatization reagent and 18.00 ml of dichloromethane, seal and protect from light, sonicate for 30 min, concentrate by nitrogen blowing, redissolve with the derivative solvent, filter and set aside. Process blank solution: Measure 19.00 ml of dichloromethane into a sample vial, add 1 ml of derivatization reagent, seal and protect from light, sonicate for 30 min, take 10.0 ml into another sample vial, blow dry with nitrogen, add 5.000 ml of derivative solvent, sonicate to dissolve, filter through a 0.22 μm filter membrane and run on the instrument; Accuracy solutions: Weigh approximately 0.1 g of the shredded sample into 5 ml sample vials, add corresponding volumes of secondary stock solution of standard, then add 1.000 ml of derivatization reagent and 18.00 ml of dichloromethane to each vial, seal and sonicate in the dark for 30 min; take 10.00 ml of each of the above solutions, blow dry with nitrogen, add 5.000 ml of derivative solvent and sonicate to dissolve, filter through a 0.22 μm filter membrane, and take approximately 1 ml into a sample vial to obtain low, medium and high concentration accuracy solutions.

[0007] Preferably, the extraction solvent in step two is one or more of dichloromethane, trichloromethane, and acetonitrile, and the derivatizing reagent is an aqueous solution of 9-(methylaminomethyl)anthracene dissolved in dichloromethane, DMF, and acetonitrile.

[0008] Preferably, the nitrogen blowing time of the nitrogen concentrator in step three is 25-35 minutes, and the nitrogen blowing temperature is controlled at 35-45°C to ensure that the solvent is fully evaporated while avoiding loss of the target substance.

[0009] Preferably, the chromatographic conditions of the ultra-high performance liquid chromatograph in step four are as follows: Column: ACQUITY UPLC BEH C18; Column temperature: 25~40℃; Fluorescence detection wavelength: excitation wavelength 254nm, emission wavelength 412nm; Flow rate: 0.30 ml / min; Injection volume: 1 μl; Mobile phase: Phase A is ammonium acetate buffer solution with pH=4.08, and Phase B is acetonitrile; Analysis time: 10~20min.

[0010] Preferably, the elution program in step four is as follows: 0.0~1.0 min, mobile phase A 50%, mobile phase B 50%; 1.0~7.0 min, mobile phase A linearly decreases from 50% to 10%, mobile phase B linearly increases from 50% to 90%; 7.0~11.0 min, mobile phase A 10%, mobile phase B 90%; 11.0~11.1 min, mobile phase A linearly increases from 10% to 50%, mobile phase B linearly decreases from 90% to 50%; 11.1~12.0 min, mobile phase A 50%, mobile phase B 50%.

[0011] Preferably, the chromatographic column has a size of 2.1 mm × 100 mm and a packing particle size of 1.7 μm.

[0012] Preferably, the linear equation in step five is: y = ax + b, where y is the peak area of ​​HMDI, x is the concentration of HMDI, a is the slope, and b is the intercept; the formula for calculating the measured value of the solution is: In the formula, A is the peak area of ​​the solution to be calculated, and a and b are the slope and intercept of the linear equation, respectively, which are used in the spiked recovery experiment for evaluating the accuracy of the method.

[0013] Preferably, the recovery rate calculation formula in the accuracy evaluation is: In the formula, the measured quantity is the measured value of the accuracy solution × the volume of the sample solution ÷ the unit conversion factor; the sample background is the average value of the sample solution × the volume of the sample solution ÷ the unit conversion factor; and the added amount is the concentration of the added test solution × the added volume ÷ the unit conversion factor.

[0014] The beneficial effects of this invention are as follows: A dedicated analytical method for HMDI leaching in medical devices containing polyurethane materials has been established, filling a gap in existing technology and solving the problem of the lack of unified standards for HMDI residue detection in the medical device industry. This provides a reliable technical means for product safety assessment. Furthermore, the use of 9-(methylaminomethyl)anthracene as a derivatization reagent allows for a specific reaction with HMDI to generate a stable fluorescent derivative. Combined with a fluorescence detector, this significantly improves the method's sensitivity and meets the detection requirements for low-concentration HMDI leaching. Detailed Implementation

[0015] Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0016] This invention provides an analytical method for determining the amount of HMDI leaching in medical devices containing polyurethane materials. The specific steps are as follows: Step 1: Solution Preparation Prepare mobile phase, diluent, derivatization reagent, derivative solvent, standard stock solution, series of standard curve solutions, process blank solution and accuracy solution; Step 2: Sample Pretreatment Take a medical device sample containing polyurethane material, remove the outer packaging and non-human contact components, cut it into pieces and weigh about 0.1g of the sample, add the extraction solvent and derivatization reagent, seal and protect from light and sonicate for 30min. Step 3: Concentration and Reconstitution Take 10.00 ml of the solution after the reaction in step two, blow it dry with nitrogen using a nitrogen blower, add the derivative solvent and dissolve it by sonication, then filter it through a 0.22 μm filter membrane to obtain the test solution; Step 4: Instrument Testing The test solution was analyzed by ultra-high performance liquid chromatography-fluorescence detection, gradient elution was performed according to a specific elution program, and the peak area of ​​HMDI was recorded. Step 5: Quantitative Calculation A standard curve is plotted with the peak area of ​​the standard curve solution as the ordinate and the concentration as the abscissa, and a linear equation is obtained. The peak area of ​​the test solution is then substituted into the equation to calculate the measured value of HMDI solution.

[0017] By standardizing solution preparation, targeted sample pretreatment, precise concentration and reconstitution, and high-efficiency instrument detection, the accurate determination of HMDI dissolution in medical devices containing polyurethane materials was achieved. Light-shielded ultrasonic derivatization reaction ensured stable HMDI conversion, nitrogen blowing concentration and membrane filtration effectively enriched the target analyte and removed matrix interference, and ultra-high performance liquid chromatography-fluorescence detection combined high sensitivity and high selectivity, while gradient elution further improved the separation effect. The overall process was standardized and the steps were closely linked, which greatly improved the accuracy and repeatability of the detection and provided reliable technical support for the safety evaluation of medical devices.

[0018] The method for preparing the solution in step one is as follows: Mobile phase A: Weigh 1.54177 g of ammonium acetate into a 1 L volumetric flask, add water to dissolve and make up to volume, adjust the pH to 4.08 with acetic acid, and sonicate for 15 min; Mobile phase B: Measure 1000 ml of acetonitrile and sonicate at room temperature for 15 min; Diluent: dichloromethane; Derivatization reagent: Weigh 26.18 mg of 9-(methylaminomethyl)anthracene into a 100 ml volumetric flask, add dichloromethane to the mark, and shake well; Derivative solvent: Measure 50 ml of N,N-dimethylformamide into a 100 ml volumetric flask, add 40 ml of acetonitrile, and dilute to the mark with purified water. Shake well. Standard stock solution: Weigh 15.135 mg HMDI standard into a 10 ml volumetric flask, dilute to volume with dichloromethane, and shake well; Secondary stock solution of standard: Transfer 166.0 μl of primary stock solution into a 5 ml volumetric flask, dilute to volume with dichloromethane, and shake well; Standard curve solutions: Take appropriate amounts of the secondary stock solution of the standard, dilute with diluent to prepare linear solutions with concentrations of 0.309 μg / ml, 0.602 μg / ml, 1.003 μg / ml, 1.504 μg / ml, and 2.006 μg / ml. Take 1.000 ml of each linear solution, mix with 1.000 ml of derivatization reagent and 18.00 ml of dichloromethane, seal and protect from light, sonicate for 30 min, concentrate by nitrogen blowing, redissolve with the derivative solvent, filter and set aside. Process blank solution: Measure 19.00 ml of dichloromethane into a sample vial, add 1 ml of derivatization reagent, seal and protect from light, sonicate for 30 min, take 10.0 ml into another sample vial, blow dry with nitrogen, add 5.000 ml of derivative solvent, sonicate to dissolve, filter through a 0.22 μm filter membrane and run on the instrument; Accuracy solutions: Weigh approximately 0.1 g of the shredded sample into 5 ml sample vials, add corresponding volumes of secondary stock solution of standard, then add 1.000 ml of derivatization reagent and 18.00 ml of dichloromethane to each vial, seal and sonicate in the dark for 30 min; take 10.00 ml of each of the above solutions, blow dry with nitrogen, add 5.000 ml of derivative solvent and sonicate to dissolve, filter through a 0.22 μm filter membrane, and take approximately 1 ml into a sample vial to obtain low, medium and high concentration accuracy solutions.

[0019] The solution preparation method of this paper precisely quantifies the component ratios of each group. The mobile phase is stabilized by pH adjustment and ultrasonic treatment to ensure elution performance. The derivatization reagent and solvent system are adapted to the characteristics of HMDI, which can efficiently realize the derivatization reaction of the target analyte. The standard stock solution is prepared in stages and a series of concentration standard curve solutions are set in gradient to meet the linear range requirements of quantitative analysis. The process blank solution and accuracy solution are prepared simultaneously, which can effectively eliminate matrix interference and verify the reliability of the method. The overall scheme is logically rigorous and the parameters are clearly defined, providing a high-purity and high-stability solution system for subsequent detection, ensuring accurate and reliable detection results.

[0020] In step two, the extraction solvent is one or more of dichloromethane, trichloromethane, and acetonitrile, and the derivatization reagent is an aqueous solution of 9-(methylaminomethyl)anthracene dissolved in dichloromethane, DMF, and acetonitrile.

[0021] The extraction solvents, either single or in combination, of dichloromethane, trichloromethane, and acetonitrile exhibit strong solubility and targeted extraction capabilities for HMDI in polyurethane materials, enabling efficient separation of the target analyte. The derivatization reagent, 9-(methylaminomethyl)anthracene, is combined with an aqueous solution of dichloromethane, DMF, and acetonitrile. This reagent rapidly undergoes a derivatization reaction with HMDI, generating a stable derivative with a strong fluorescent response. This significantly improves detection sensitivity and specificity, laying the foundation for subsequent precise quantification.

[0022] In step three, the nitrogen blowing time of the nitrogen concentrator is 25-35 minutes, and the nitrogen blowing temperature is controlled at 35-45℃ to ensure that the solvent is fully evaporated while avoiding the loss of the target substance.

[0023] These conditions ensure that solvents such as dichloromethane fully evaporate, achieving efficient enrichment of the target derivatives; they also prevent the decomposition and loss of the target substance due to excessively high temperature or prolonged time, or the introduction of matrix interference due to insufficient concentration; precise parameter control ensures the purity of the test solution and the recovery rate of the target substance, significantly improving the accuracy and repeatability of subsequent detection results.

[0024] The chromatographic conditions for the ultra-high performance liquid chromatograph in step four are as follows: Column: ACQUITY UPLC BEH C18; Column temperature: 25~40℃; Fluorescence detection wavelength: excitation wavelength 254nm, emission wavelength 412nm; Flow rate: 0.30 ml / min; Injection volume: 1 μl; Mobile phase: Phase A is ammonium acetate buffer solution with pH=4.08, and Phase B is acetonitrile; Analysis time: 10~20min.

[0025] The ACQUITY UPLC BEH C18 column, coupled with a column temperature of 25–40 °C and a flow rate of 0.30 ml / min, achieves efficient separation of target derivatives. The fluorescence detection wavelength is precisely matched to the characteristics of the derivatives, with an excitation wavelength of 254 nm and an emission wavelength of 412 nm, which greatly improves the detection sensitivity and specificity. The 1 μl micro-injection reduces matrix interference, and the 10–20 min analysis time balances detection efficiency and separation effect, providing reliable instrumental support for the accurate determination of HMDI dissolution.

[0026] The elution program in step four is as follows: 0.0~1.0 min, mobile phase A 50%, mobile phase B 50%; 1.0~7.0 min, mobile phase A linearly decreases from 50% to 10%, mobile phase B linearly increases from 50% to 90%; 7.0~11.0 min, mobile phase A 10%, mobile phase B 90%; 11.0~11.1 min, mobile phase A linearly increases from 10% to 50%, mobile phase B linearly decreases from 90% to 50%; 11.1~12.0 min, mobile phase A 50%, mobile phase B 50%.

[0027] The initial ratio of 50% mobile phase A to 50% mobile phase B enables preliminary separation of components in the sample. Linear adjustment of the phase ratio over 1.0 to 7.0 min effectively promotes the efficient separation of target derivatives and matrix impurities. Maintaining a constant high proportion of organic phase over 7.0 to 11.0 min thoroughly elutes strongly retained impurities. The subsequent rapid reset and maintenance of the initial ratio ensures column equilibration and stability for the next injection. The overall program balances separation performance and detection efficiency, avoiding peak broadening and tailing issues, and significantly improving the accuracy and repeatability of detection results.

[0028] The chromatographic column has a size of 2.1 mm × 100 mm and a packing particle size of 1.7 μm.

[0029] The chromatographic column uses a 2.1 mm × 100 mm specification with a 1.7 μm packing particle size, which combines high column efficiency and rapid separation characteristics; the narrow column diameter reduces mobile phase consumption, and the short column body shortens the analysis time; the small particle size packing increases the separation surface area, improves the separation degree between target analytes and impurities, avoids peak overlap interference, and ensures accurate and reliable detection results.

[0030] In step five, the linear equation is: y = ax + b, where y is the peak area of ​​HMDI, x is the concentration of HMDI, a is the slope, and b is the intercept; the formula for calculating the measured value of the solution is: In the formula, A is the peak area of ​​the solution to be calculated, and a and b are the slope and intercept of the linear equation, respectively, which are used in the spiked recovery experiment for evaluating the accuracy of the method.

[0031] A linear equation, y=ax+b, is used to establish a quantitative relationship between peak area and concentration. The model has a high degree of fit and clear calculation logic. The accompanying calculation formula can infer the concentration from the peak area and can be directly applied to evaluate the accuracy of spiked recovery experiments. It can quickly quantify the method recovery rate and error range. The combination of linear fitting and quantitative calculation ensures the accuracy and traceability of HMDI dissolution measurement results.

[0032] The formula for calculating the recovery rate in the accuracy evaluation is as follows: In the formula, the measured quantity is the measured value of the accuracy solution × the volume of the sample solution ÷ the unit conversion factor; the sample background is the average value of the sample solution × the volume of the sample solution ÷ the unit conversion factor; and the added amount is the concentration of the added test solution × the added volume ÷ the unit conversion factor.

[0033] The formula incorporates key parameters such as sample solution volume and unit conversion factor, eliminating volume conversion errors during pretreatment and detection, and ensuring the accuracy and comparability of the calculation results. This formula can be directly used for the quantitative evaluation of method accuracy, providing a standardized calculation basis for verifying the reliability of the detection method and ensuring the scientific validity of the HMDI dissolution measurement results.

[0034] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0035] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An analytical method for determining the amount of HMDI leaching in medical devices containing polyurethane materials, characterized in that, The specific steps are as follows: Step 1: Solution Preparation Prepare mobile phase, diluent, derivatization reagent, derivative solvent, standard stock solution, series of standard curve solutions, process blank solution and accuracy solution; Step 2: Sample Pretreatment Take a medical device sample containing polyurethane material, remove the outer packaging and non-human contact components, cut it into pieces and weigh about 0.1g of the sample, add the extraction solvent and derivatization reagent, seal and protect from light and sonicate for 30min. Step 3: Concentration and Reconstitution Take 10.00 ml of the solution after the reaction in step two, blow it dry with nitrogen using a nitrogen blower, add the derivative solvent and dissolve it by sonication, then filter it through a 0.22 μm filter membrane to obtain the test solution; Step 4: Instrument Testing The test solution was analyzed by ultra-high performance liquid chromatography-fluorescence detection, gradient elution was performed according to a specific elution program, and the peak area of ​​HMDI was recorded. Step 5: Quantitative Calculation A standard curve is plotted with the peak area of ​​the standard curve solution as the ordinate and the concentration as the abscissa, and a linear equation is obtained. The peak area of ​​the test solution is then substituted into the equation to calculate the measured value of HMDI solution.

2. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 1, characterized in that: The method for preparing the solution described in step one is as follows: Mobile phase A: Weigh 1.54177 g of ammonium acetate into a 1 L volumetric flask, add water to dissolve and make up to volume, adjust the pH to 4.08 with acetic acid, and sonicate for 15 min; Mobile phase B: Measure 1000 ml of acetonitrile and sonicate at room temperature for 15 min; Diluent: dichloromethane; Derivatization reagent: Weigh 26.18 mg of 9-(methylaminomethyl)anthracene into a 100 ml volumetric flask, add dichloromethane to the mark, and shake well; Derivative solvent: Measure 50 ml of N,N-dimethylformamide into a 100 ml volumetric flask, add 40 ml of acetonitrile, and dilute to the mark with purified water. Shake well. Standard stock solution: Weigh 15.135 mg HMDI standard into a 10 ml volumetric flask, dilute to volume with dichloromethane, and shake well; Secondary stock solution of standard: Transfer 166.0 μl of primary stock solution into a 5 ml volumetric flask, dilute to volume with dichloromethane, and shake well; Standard curve solutions: Take appropriate amounts of the secondary stock solution of the standard, dilute with diluent to prepare linear solutions with concentrations of 0.309 μg / ml, 0.602 μg / ml, 1.003 μg / ml, 1.504 μg / ml, and 2.006 μg / ml. Take 1.000 ml of each linear solution, mix with 1.000 ml of derivatization reagent and 18.00 ml of dichloromethane, seal and protect from light, sonicate for 30 min, concentrate by nitrogen blowing, redissolve with the derivative solvent, filter and set aside. Process blank solution: Measure 19.00 ml of dichloromethane into a sample vial, add 1 ml of derivatization reagent, seal and protect from light, sonicate for 30 min, take 10.0 ml into another sample vial, blow dry with nitrogen, add 5.000 ml of derivative solvent, sonicate to dissolve, filter through a 0.22 μm filter membrane and run on the instrument; Accuracy solutions: Weigh approximately 0.1 g of the shredded sample into 5 ml sample vials, add corresponding volumes of secondary stock solution of standard, then add 1.000 ml of derivatization reagent and 18.00 ml of dichloromethane to each vial, seal and sonicate in the dark for 30 min; take 10.00 ml of each of the above solutions, blow dry with nitrogen, add 5.000 ml of derivative solvent and sonicate to dissolve, filter through a 0.22 μm filter membrane, and take approximately 1 ml into a sample vial to obtain low, medium and high concentration accuracy solutions.

3. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 1, characterized in that: The extraction solvent in step two is one or more of dichloromethane, trichloromethane, and acetonitrile, and the derivatization reagent is an aqueous solution of 9-(methylaminomethyl)anthracene dissolved in dichloromethane, DMF, and acetonitrile.

4. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 1, characterized in that: In step three, the nitrogen blowing time of the nitrogen concentrator is 25-35 minutes, and the nitrogen blowing temperature is controlled at 35-45℃ to ensure that the solvent is fully evaporated while avoiding the loss of the target substance.

5. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 1, characterized in that: The chromatographic conditions for the ultra-high performance liquid chromatograph described in step four are as follows: Column: ACQUITY UPLC BEH C18; Column temperature: 25~40℃; Fluorescence detection wavelength: excitation wavelength 254nm, emission wavelength 412nm; Flow rate: 0.30 ml / min; Injection volume: 1 μl; Mobile phase: Phase A is ammonium acetate buffer solution with pH=4.08, and Phase B is acetonitrile; Analysis time: 10~20min.

6. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 1, characterized in that: The elution program described in step four is as follows: 0.0~1.0 min, mobile phase A 50%, mobile phase B 50%; From 1.0 to 7.0 min, mobile phase A linearly decreased from 50% to 10%, while mobile phase B linearly increased from 50% to 90%; from 7.0 to 11.0 min, mobile phase A was 10% and mobile phase B was 90%; from 11.0 to 11.1 min, mobile phase A linearly increased from 10% to 50%, while mobile phase B linearly decreased from 90% to 50%; from 11.1 to 12.0 min, mobile phase A was 50% and mobile phase B was 50%.

7. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 5, characterized in that: The chromatographic column has dimensions of 2.1 mm × 100 mm and a packing particle size of 1.7 μm.

8. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 1, characterized in that: The linear equation described in step five is: y = ax + b, where y is the peak area of ​​HMDI, x is the concentration of HMDI, a is the slope, and b is the intercept; the formula for calculating the measured value of the solution is: In the formula, A is the peak area of ​​the solution to be calculated, and a and b are the slope and intercept of the linear equation, respectively, which are used in the spiked recovery experiment for evaluating the accuracy of the method.

9. The analytical method for determining the HMDI leaching amount in a medical device containing polyurethane materials according to claim 8, characterized in that: The formula for calculating the recovery rate in the accuracy evaluation is as follows: In the formula, the measured quantity is the measured value of the accuracy solution × the volume of the sample solution ÷ the unit conversion factor; The sample background is calculated as the average value of the sample solution measured × the volume of the sample solution ÷ the unit conversion factor. The amount added is calculated as the concentration of the added test solution × the volume added ÷ the unit conversion factor.

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