Method for testing leached substance MDA in alloy coating central venous catheter suite

Abstract

The invention relates to the field of analysis and inspection, in particular to a method for testing leached matter MDA in an alloy coating central venous catheter suite. Through three-concentration gradient accuracy solution design, a full-scale detection scene is covered, domestic and overseas standard requirements such as YY / T 1550.2-2019 are met, high specificity, sensitivity and reliability are achieved, complex matrix interference of the catheter suite can be accurately dealt with, compliance data support is provided for product safety evaluation, and the method is suitable for popularization and application. The method can be effectively used for quantitative detection of the leaching amount of MDA in the alloy coating central venous catheter suite.

Description

Technical Field

[0001] This invention relates to the field of analytical testing, and more particularly to a method for testing the leachable material MDA in an alloy-coated central venous catheter kit. Background Technology

[0002] Disposable central venous catheter kits are commonly used interventional medical devices in clinical practice, widely applied in scenarios such as intravenous infusion, nutritional support, and hemodynamic monitoring. Their direct and prolonged contact with the human body places stringent requirements on safety and biocompatibility. Alloy coatings, as a key process for improving the catheter's wear resistance, biocompatibility, and antibacterial properties, may produce leachable substances during the manufacturing process due to factors such as the material's composition, processing residues, or coating aging. These leachable substances can migrate into the human body environment. If the leachable substance content exceeds the standard, it may trigger safety risks such as inflammatory reactions and tissue damage. Therefore, accurate detection of leachable substances in catheter kits is crucial.

[0003] 4,4'-Diaminodiphenylmethane (MDA, CAS No.: 101-77-9) is a typical leachable substance that may be generated during the processing or use of alloy coatings and related polymer materials. It has certain biotoxicity, and its migration level is directly related to the safety of medical devices. Currently, relevant standards have been established both domestically and internationally for the detection of leachable substances in medical devices, requiring the development of highly specific, sensitive, and accurate analytical methods to achieve precise quantification of target leachable substances and provide data support for product safety evaluation.

[0004] Among existing methods for analyzing leachable substances (MDA), ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS / MS) is the preferred solution for detecting trace contaminants in complex matrices due to its combination of high separation efficiency and high detection sensitivity. However, for a specific product like a disposable alloy-coated central venous catheter kit, the matrix composition is complex, and the interaction between the alloy coating and the extraction solvent may interfere with the detection of MDA. Furthermore, there is a lack of systematic analytical method validation data specifically for MDA in this product, making it difficult to guarantee the reliability and accuracy of the detection results. Therefore, there is an urgent need to establish a fully validated UPLC-MS / MS analytical method, clarifying key indicators such as specificity, linearity, limit of quantitation, and accuracy, to ensure accurate determination of the leachable amount of MDA in this catheter kit and meet the technical requirements for medical device-drug compatibility studies. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a method for testing the leachable material MDA in alloy-coated central venous catheter kits, comprising the following steps: S1. Remove the part of the disposable alloy-coated central venous catheter that is not in contact with the human body, cut it, put it into a polytetrafluoroethylene bottle, add solvent, extract, and obtain sample mother liquor; S2. Prepare blank sample stock solution and accuracy solution; S3. Based on the sample stock solution, blank sample stock solution, and accuracy solution, UPLC-MS / MS was used to perform quantitative analysis of MDA.

[0006] In this invention, the alloy-coated central venous catheter is used in a manner that involves direct or indirect contact. The other parts are not in contact with the human body, which generally depends on the actual use of the medical device.

[0007] The matrix composition of disposable alloy-coated central venous catheter kits is complex. The interaction between the alloy coating and the extraction solvent can easily generate interfering substances. Although existing UPLC-MS / MS technology is suitable for the detection of trace contaminants, it lacks a specific method for this particular product. Interfering substances can easily overlap with MDA during detection, affecting the accuracy of the results and making it difficult to accurately identify and quantify MDA. At the same time, the leachable amount of MDA is significantly uncertain due to factors such as fluctuations in manufacturing processes, batch differences in materials, and changes in storage conditions. It may present different scenarios such as trace amounts, normal amounts, and critical amounts. Traditional detection methods that validate at a single concentration cannot cover the accuracy requirements of the entire concentration range. Low concentrations are easily affected by background noise, and high concentrations may experience response saturation, leading to quantitative deviations. Furthermore, the detection of leachable matter in medical devices must comply with YY / T 1550.2-2019, Appendix 9101 of Part IV of the 2025 Edition of the Chinese Pharmacopoeia, and ICH Q2. Authoritative domestic and international standards such as (R2) require systematic verification of key indicators such as limit of quantitation, accuracy, and precision. Existing methods lack complete verification data for this catheter kit, making it difficult to use the test results as a compliance basis for product safety evaluation. In addition, traditional testing methods do not fully consider the impact of catheter sample processing characteristics on MDA migration, and do not verify the interference of solution stability and instrument parameter fluctuations on the results. As a result, the methods are prone to poor repeatability and insufficient stability in practical applications, and cannot meet the needs of production quality control.

[0008] As an example of an feasible approach, the cut dimensions are 5-20mm × 40-60mm.

[0009] As an example of implementation, the solvent includes an aqueous solution of ethanol.

[0010] Furthermore, the mass concentration of the ethanol aqueous solution is 40-50 wt%.

[0011] Furthermore, the amount of solvent added is 50-100 mL.

[0012] As an example of implementation, the extraction temperature is 45-60°C.

[0013] As an example of an feasible approach, the extraction time is 7-14 days.

[0014] By removing the parts of the catheter that do not come into contact with the human body, and retaining only the key contact area, and cutting it into standardized sample blocks of 5-20mm × 40-60mm, the samples are ensured to truly reflect the MDA migration scenario in clinical use, avoiding interference from impurities introduced from non-contact parts. Regarding the specific extraction conditions, a 40-50wt% ethanol aqueous solution is selected as the solvent, and the extraction temperature is controlled at 45-60℃ for 7-14 days. This ensures that MDA is fully migrated into the solution, while avoiding the degradation of the coating caused by high temperature or strong solvents, which would generate additional interfering substances. At the same time, an inert polytetrafluoroethylene bottle is used to reduce container contamination of the sample.

[0015] As an feasible example, the method for preparing the blank sample mother liquor includes: adding a solvent to a polytetrafluoroethylene bottle and extracting to obtain the blank sample mother liquor.

[0016] As an implementable example, the accuracy solution includes low-concentration level accuracy solution, medium-concentration level accuracy solution, and high-concentration level accuracy solution.

[0017] Furthermore, the method for preparing the low-concentration level accuracy solution includes the following steps: Dissolve MDA in acetonitrile to prepare a 10-20 μg / mL MDA standard solution. Measure 700-800 μL of the sample stock solution into a 1 mL volumetric flask, add 20-50 μL of the MDA standard solution, and make up to volume to obtain a low-concentration accuracy solution.

[0018] Furthermore, the method for preparing the medium-concentration level accuracy solution includes the following steps: Dissolve MDA in acetonitrile to prepare a 10-20 μg / mL MDA standard solution. Measure 700-800 μL of the sample stock solution into a 1 mL volumetric flask, add 80-120 μL of the MDA standard solution, and make up to volume to obtain a medium concentration level accuracy solution.

[0019] Furthermore, the method for preparing the high-concentration level accuracy solution includes the following steps: Dissolve MDA in acetonitrile to prepare a 10-20 μg / mL MDA standard solution. Measure 700-800 μL of the sample stock solution into a 1 mL volumetric flask, add 125-200 μL of the MDA standard solution, and make up to volume to obtain a high-concentration accuracy solution.

[0020] This invention defines accuracy solutions with low, medium, and high concentration levels primarily to cover the full concentration range of actual testing scenarios and meet industry technical specifications. The leachable amount of MDA in disposable alloy-coated central venous catheter kits exhibits significant uncertainty due to factors such as manufacturing process fluctuations, batch-to-batch material differences, and changes in storage conditions. Low concentrations correspond to scenarios with low migration, medium concentrations align with common ranges in routine testing, and high concentrations address critical situations approaching or slightly exceeding the method's limit of quantitation. Through three-gradient concentration validation, accurate results can be obtained for samples with varying degrees of contamination. Furthermore, authoritative domestic and international standards such as YY / T 1550.2-2019, Appendix 9101 of the 2025 edition of the Chinese Pharmacopoeia, and ICH Q2 (R2) explicitly require accuracy validation to examine the reliability of multiple concentration levels. Limiting the concentration to three gradients is a necessary design to comply with regulations, ensuring the integrity and compliance of method validation, and giving the results industry recognition and legal validity.

[0021] On the other hand, designing low, medium, and high concentration solutions allows for a comprehensive examination of the linear response and anti-interference capabilities of the analytical method, thereby improving its reliability. At different concentrations, the response relationship between the target analyte MDA and the detection system, as well as the degree of matrix interference, vary: low concentrations are easily affected by the instrument's detection limit and background noise; high concentrations may exhibit response saturation and peak distortion; while medium concentrations reflect typical response characteristics. By separately validating the accuracy of the three concentration levels, the linear response stability, concentration dependence of matrix interference, and spike recovery uniformity of the method can be systematically evaluated, avoiding the limitations of single-concentration validation and fundamentally ensuring the quantitative stability and applicability of the method across the entire range.

[0022] As an example of implementation, the UPLC-MS / MS column flow rate is 0.1-0.5 mL / min.

[0023] As an example of implementation, the column temperature of the UPLC-MS / MS is 30-40℃.

[0024] As an implementable example, the mobile phase A of the UPLC-MS / MS comprises an aqueous acetic acid solution, and the mobile phase B comprises acetonitrile.

[0025] Furthermore, the mass concentration of the acetic acid aqueous solution is 0.01-0.1 wt%.

[0026] As an example of implementation, the scanning wavelength range of the UPLC-MS / MS is 190~400nm.

[0027] Beneficial effects (i) This invention, through a three-concentration gradient design of low, medium and high, is fully adapted to the uncertainty of the amount of MDA that can be leachable in disposable alloy-coated central venous catheter kits (such as trace amounts, regular amounts, critical amounts, etc.), ensuring that samples with different levels of contamination can obtain accurate detection results and avoiding quantitative deviations caused by concentration differences.

[0028] (ii) This invention strictly follows the accuracy verification requirements of domestic and international standards such as YY / T1550.2-2019, Appendix 9101 of Part IV of the 2025 edition of the Chinese Pharmacopoeia and ICHQ2 (R2), ensuring that the method verification process is complete and the data is compliant, providing technical support with industry recognition and legal effect for product safety evaluation.

[0029] (iii) This invention uses multi-concentration gradient verification to systematically evaluate the linear response law of the target substance and the detection system, confirm the consistency of the response relationship across the entire range, avoid the one-sidedness caused by single-concentration verification, and ensure the rigor of the quantitative logic of the method.

[0030] (iv) To address the differences in matrix interference levels and instrument response characteristics at different concentrations, including resistance to background noise at low concentrations and resistance to response saturation at high concentrations, the method’s anti-interference performance was fully verified to ensure stable quantification in complex matrix environments of catheter kits and to improve the method’s practical applicability.

[0031] (v) Through spiked recovery verification at three concentration levels, the recovery uniformity and RSD stability of the method are confirmed throughout the entire range, providing a reliable detection method for MDA migration fluctuations caused by factors such as process fluctuations, material batch differences, and changes in storage conditions during the production process, and helping to control product quality throughout the entire process. Attached Figure Description

[0032] Figure 1 This is the chromatogram of the blank reagent solution.

[0033] Figure 2 The chromatogram is for the L-3 sample solution.

[0034] Figure 3 This is the chromatogram of the sample solution.

[0035] Figure 4 This is a chromatogram of a solution spiked at the limit of quantitation.

[0036] Figure 5 This is the chromatogram of a blank sample solution. Detailed Implementation

[0037] Example 1 This example provides a testing method for the leachable material MDA in an alloy-coated central venous catheter kit, specifically comprising the following steps: This embodiment uses UPLC-MS / MS to validate the analytical method for known leachable organic matter (MDA) in disposable alloy-coated central venous catheter kits. All validation parameters met the acceptance criteria in this experiment. The specific validation details are shown in Table 1.

[0038] Table 1

[0039] Sample to be tested: Disposable alloy-coated central venous catheter kit, model number 7Fr×30 (three-lumen), manufactured by Guangzhou Weili Medical Instrument Co., Ltd.; the purity of MDA is 97.16%.

[0040] In this example, the MDA standard solutions required include MDA standard solution A and MDA standard solution B, both with an MDA mass concentration of 12.00 μg / mL and acetonitrile as the solvent.

[0041] In this example, the ultra-high performance liquid chromatograph-mass spectrometer used in the test was an ACQuity I CLASS & TRIPLE QUAD 5500+, purchased from Waters Technology (Shanghai) Co., Ltd. & Shanghai Aibocaisi Analytical Instruments Trading Co., Ltd.; the ultrapure water system was a Direct 8, purchased from Millipore (China) Co., Ltd.; the ultrasonic cleaner was a KQ-300DE, purchased from Kunshan Ultrasonic Instruments Co., Ltd.; and the isothermal incubator shaker was a ZWYR-200D, purchased from Shanghai Zhicheng Analytical Instruments Manufacturing Co., Ltd.

[0042] In this example, the specific information regarding the limit values ​​of the target object in the MDA is shown in Table 2.

[0043] Table 2

[0044] According to the table below, measure the MDA standard substance solution into 10mL volumetric flasks, dilute to the mark with acetonitrile, shake well, and prepare the standard curve solution. The specific preparation table of the standard curve solution is shown in Table 3.

[0045] Table 3

[0046] The concentrations of the standard substances in the standard curve solutions are shown in Table 4.

[0047] Table 4

[0048] In this example, the System Suitability (SST) solution is to take approximately 1 mL of L-3 solution into the vial.

[0049] The quality control (QC) solution is prepared by taking approximately 1 mL of L-3 solution and injecting it into a vial.

[0050] The limit of quantitation (LOQ) solution uses an L⁻¹ solution as the limit of quantitation solution.

[0051] The sample mother liquor was prepared by taking three sets of disposable alloy-coated central venous catheter kits, selecting disposable alloy-coated central venous catheter components, removing the parts that do not come into contact with the human body, cutting them according to GB / T 16886-12, preparing sample blocks of 10 mm × 50 mm, placing them in polytetrafluoroethylene bottles, adding 54 mL of 40wt% ethanol-water mixture, capping, and extracting at 50 ℃ for 13 days.

[0052] The blank sample stock solution was prepared by adding 54 mL of 40 wt% ethanol aqueous solution to a 150 mL polytetrafluoroethylene bottle, capping the bottle, and extracting at 50 °C for 13 days. The extract was then collected for later use.

[0053] The sample solution was prepared by measuring 750.0 μL of the sample stock solution into a 1 mL volumetric flask, diluting it to the mark with diluent, shaking well, and taking about 1 mL of the solution into a sample injection bottle; two sample solutions were prepared in parallel using the same method to obtain sample solution 1 and sample solution 2.

[0054] To prepare the blank sample solution, measure 750.0 μL of the blank sample stock solution into a 1 mL volumetric flask, dilute to the mark with diluent, shake well, and then take about 1 mL of the solution into a sample injection bottle.

[0055] The reagent blank solution is prepared by measuring 750.0 μL of acetonitrile into a 1 mL volumetric flask, diluting to the mark with diluent, and shaking well.

[0056] In this example, the accuracy solution includes low-concentration level accuracy solution, medium-concentration level accuracy solution, and high-concentration level accuracy solution.

[0057] The method for preparing the low-concentration level accuracy solution is as follows: Measure 750.0 μL of the sample stock solution into a 1 mL volumetric flask, add 25.0 μL of standard substance solution A, dilute to the mark with diluent, and shake well. Take approximately 1 mL of the solution into a sample vial. Prepare three parallel solutions using the same method to obtain low-concentration level accuracy solution 1 to low-concentration level accuracy solution 3. The mass concentration of MDA in the low-concentration level accuracy solution is 300 μg / L.

[0058] The preparation method for the medium concentration level accuracy solution is as follows: 750.0 μL of the sample stock solution is measured into a 1 mL volumetric flask, 100.0 μL of standard substance solution A is added, and the solution is diluted to the mark with diluent and shaken well. Approximately 1 mL of the solution is then transferred to a sample vial. Three parallel solutions are prepared using the same method to obtain medium concentration level accuracy solutions 1 through 3. The mass concentration of MDA in the medium concentration level accuracy solution is 1200 μg / L.

[0059] The high-concentration level accuracy solution was prepared as follows: 750.0 μL of the sample stock solution was measured into a 1 mL volumetric flask, 150.0 μL of standard substance solution A was added, and the solution was diluted to the mark with diluent and shaken well. Approximately 1 mL of the solution was then transferred to a sample vial. Three parallel solutions were prepared using the same method to obtain high-concentration level accuracy solution 1 through high-concentration level accuracy solution 3. The mass concentration of MDA in the high-concentration level accuracy solution was 1800 μg / L.

[0060] The quantitation limit spiking solutions were selected from low-concentration level accuracy solutions 1 to low-concentration level accuracy solutions 3 as quantitation limit spiking solutions 1 to quantitation limit spiking solutions 3.

[0061] The specific solutions used were reagent blank solution, blank sample solution, sample solution 1, standard curve solution (sequence L-3) and limit of quantitation spiked solution.

[0062] For the precision-reproducibility solution, measure 750.0 μL of the sample stock solution into a 1 mL volumetric flask, add 100.0 μL of standard substance solution A, dilute to the mark with diluent, and mix well. Transfer approximately 1 mL of this solution to a sample vial. Prepare six parallel solutions using the same method to obtain reproducibility solutions 1 through 6.

[0063] In this example, the durable solution is the L-3 solution.

[0064] The solution stability solution is prepared by taking the above repeatable solutions 1 to 6 and placing them at room temperature (25°C) for 20 hours to obtain solution stability solutions 1 to 6 in sequence.

[0065] The intermediate precision solution was prepared by measuring 750.0 μL of the sample stock solution into a 1 mL volumetric flask, adding 100.0 μL of standard substance solution B, diluting to the mark with diluent, and shaking well. Approximately 1 mL of the solution was then transferred to a sample vial. Six parallel solutions were prepared using the same method to obtain intermediate precision solutions 1 through 6.

[0066] The specific chromatographic parameters for UPLC-MS / MS in this example are shown in Table 5.

[0067] Table 5

[0068] The specific parameters for setting the mobile phase are shown in Table 6.

[0069] Table 6

[0070] In Table 6, the linear representation at 0 min is the elution gradient curve of the instrument, which is the default setting of the equipment program. Elution has not started at 0.0 min, so it is not used, i.e., N / A. Subsequent elution will proceed according to the normal curve.

[0071] In this example, the repeatability of MDA injection was evaluated by the RSD of the target peak area in the SST solution. The RSD result was rounded to the nearest integer. The specific experimental results are shown in Table 7.

[0072] Table 7

[0073] Quality control is evaluated by the RSD of the peak area of ​​the target substance in the SST solution and the quality control solution. The tRSD of QC-n is the tRSD of the peak area of ​​the target substance in the SST solution and n quality control solutions. The tRSD result is rounded to the nearest integer. The specific test results are shown in Table 8.

[0074] Table 8

[0075] The relative standard deviation (RSD%) is calculated as follows: peak area standard deviation (SD) ÷ average peak area (x) × 100%.

[0076] Standard deviation (SD) = [∑(x i -x) 2 ÷(n-1)] 1 / 2 x i Let x be the i-th data value, and let x be the average value.

[0077] The specific acceptance criteria and results of MDA in this example are shown in Table 9-10.

[0078] Table 9

[0079] Table 10

[0080] The chromatogram of the blank reagent solution is shown below. Figure 1 As shown, the chromatogram of the L-3 sample solution is as follows: Figure 2 The chromatogram of the sample solution is as follows: Figure 3 As shown, the chromatogram of the quantitation limit spiked solution is as follows: Figure 4 As shown, the chromatogram of the blank sample solution is as follows: Figure 5 As shown.

[0081] 1. Linear Relationship Analysis In this example, the linear regression equation for MDA detection was automatically calculated by the instrument software, with the correlation coefficient retained to three decimal places, as shown in Table 11.

[0082] Table 11

[0083] 2. Limit of Quantification Analysis Report the signal-to-noise ratio of the target analyte in the limit-of-quantitation (LOQ) solution, rounding the results to the nearest integer. Calculate the recovery rate and RSD of the target analyte in the LOQ spiked solution, rounding the recovery and RSD results to the nearest integer. The acceptance criteria and results for the LOQ are shown in Table 12, and the acceptance criteria and results for the LOQ spiked solution are shown in Table 13.

[0084] Table 12

[0085] Wherein, the method limit of quantitation (μg / L) = limit of quantitation solution (μg / L) × final volume (mL) ÷ sampling volume (mL) × unit conversion factor.

[0086] 3. Accuracy Analysis If the reported result is less than the limit of quantitation, it should be reported as "specific value of the limit of quantitation". If it is greater than the limit of quantitation, the actual result should be reported. The unit of the reported value is μg / L, and the number of decimal places should be consistent with the limit value. The specific test results of the sample are shown in Table 13.

[0087] Table 13

[0088] The accuracy results for the MDA solution are shown in Table 14, and the acceptance criteria and results for the accuracy are shown in Table 15.

[0089] Table 14

[0090] Table 15

[0091] In the table above, the formula for calculating the sample results is: average value of sample solution (μg / L) = (value of sample solution 1 (μg / L) + value of sample solution 2 (μg / L)) ÷ 2; Reported value (μg / L) = Average value of sample solution (μg / L) × Final volume (mL) ÷ Sampling volume (mL).

[0092] The formula for calculating accuracy is: Background (μg) = Average value of sample solution (μg / L) × Sample solution volume (mL) ÷ Unit conversion factor; Added amount (μg) = Added test solution concentration (μg / mL) × Added volume (μL) ÷ Unit conversion factor; Measured amount (μg) = Accuracy solution measured value (μg / L) × Sample solution volume (mL) ÷ Unit conversion factor; Recovery rate = (Measured amount (μg) - Background (μg)) ÷ Added (μg) × 100%; When the target analyte is not detected in the sample solution, the recovery rate is calculated with a background of 0.000.

[0093] 4. Precision analysis This test primarily characterizes the precision of the test method, i.e., repeatability. The acceptance criteria for repeatability and the specific results are shown in Table 16. The RSD of the measured values ​​is retained to the integer part.

[0094] Table 16

[0095] In the test results in Table 16, the relative standard deviation (RSD) = peak area standard deviation (SD) ÷ peak area average (x) × 100%, and the standard deviation (SD) = [∑(x) i -x) 2 ÷(n-1)] 1 / 2 x i Let x be the i-th data value, and let x be the average value.

[0096] 5. Intermediate precision analysis The RSD values ​​of 6 intermediate precision solutions and 6 repeatability solutions (a total of 12 solutions) were retained to integer values ​​to test the intermediate precision of the MDA detection method. The specific test results are detailed in Table 17.

[0097] Table 17

[0098] In the test results in Table 17, the relative standard deviation (RSD) = peak area standard deviation (SD) ÷ peak area average (x) × 100%, and the standard deviation (SD) = [∑(x) i -x) 2 ÷(n-1)] 1 / 2 x i Let x be the i-th data value, and let x be the average value.

[0099] 6. Solution stability analysis The solution stability of the leachable material MDA in the alloy-coated central venous catheter kit was tested. The experimental results are detailed in Table 18.

[0100] Table 18

[0101] In the test results in Table 18, the relative standard deviation (RSD) = peak area standard deviation (SD) ÷ peak area average (x) × 100%, and the standard deviation (SD) = [∑(x) i -x) 2 ÷(n-1)] 1 / 2 x i Let x be the i-th data value, and let x be the average value.

[0102] 7. Durability Analysis The robustness of the leachable material MDA method in the alloy-coated central venous catheter kit was tested. The test results at a column flow rate of 0.330 mL / min are detailed in Table 19, and the test results at a column flow rate of 0.270 mL / min are detailed in Table 20.

[0103] Table 19

[0104] Table 20

[0105] In the test results in Table 19-20, the relative standard deviation (RSD) = peak area standard deviation (SD) ÷ peak area average (x) × 100%, and the standard deviation (SD) = [∑(x) i -x) 2 ÷(n-1)] 1 / 2 x i Let x be the i-th data value, and let x be the average value.

[0106] In summary, the analysis of the experimental results from tests 1-7 shows that the analytical method provided in this application can be used to determine the known leachable material MDA in disposable alloy-coated central venous catheter kits. The test results have high accuracy, high precision, and excellent test stability.

Claims

1. A method for testing the leachable material MDA in an alloy-coated central venous catheter kit, characterized in that, Includes the following steps: S1. Remove the part of the disposable alloy-coated central venous catheter that is not in contact with the human body, cut it, put it into a polytetrafluoroethylene bottle, add solvent, extract, and obtain sample mother liquor; S2. Prepare blank sample stock solution and accuracy solution; S3. Based on the sample stock solution, blank sample stock solution, and accuracy solution, UPLC-MS / MS was used to perform quantitative analysis of MDA.

2. The test method for leachable material MDA in the alloy-coated central venous catheter kit according to claim 1, characterized in that, The solvent includes an aqueous solution of ethanol.

3. The test method for leachable material MDA in the alloy-coated central venous catheter kit according to claim 2, characterized in that, The mass concentration of the ethanol aqueous solution is 40-50 wt%.

4. The test method for leachable material MDA in the alloy-coated central venous catheter kit according to claim 1, characterized in that, The extraction temperature is 45-60℃.

5. The test method for leachable material MDA in the alloy-coated central venous catheter kit according to claim 4, characterized in that, The extraction time is 7-14 days.

6. The method for testing the leachable material MDA in the alloy-coated central venous catheter kit according to claim 1, characterized in that, The method for preparing the blank sample mother liquor includes: Add solvent to a polytetrafluoroethylene bottle and extract to obtain blank sample mother liquor.

7. The test method for leachable material MDA in the alloy-coated central venous catheter kit according to claim 1, characterized in that, The scanning wavelength range of the UPLC-MS / MS is 190~400nm.

8. The method for testing the leachable material MDA in the alloy-coated central venous catheter kit according to claim 1, characterized in that, The column flow rate of the UPLC-MS / MS is 0.1-0.5 mL / min.

9. The method for testing the leachable material MDA in the alloy-coated central venous catheter kit according to claim 1, characterized in that, The mobile phase A of the UPLC-MS / MS comprises an aqueous solution of acetic acid, and the mobile phase B comprises acetonitrile.

10. The method for testing the leachable material MDA in the alloy-coated central venous catheter kit according to claim 9, characterized in that, The mass concentration of the acetic acid aqueous solution is 0.01-0.1 wt%.

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