Rapid determination method for content of aluminum adjuvant in vaccine

Abstract

The invention belongs to the technical field of detection, and particularly relates to a method for rapidly determining the content of an aluminum adjuvant in a vaccine. According to the invention, preparation and test conditions of a heterogeneous liquid sample are systematically explored by adopting a monochromatic focusing-energy dispersion X-ray fluorescence spectrum technology, and an analysis method for rapidly determining the aluminum content in the vaccine is established according to the preparation and test conditions. Compared with a classic spectrum method, the method has the remarkable advantages that the relative error absolute value is controlled within 10%, high accuracy and good precision are ensured, and meanwhile the detection limit is low. The method fully meets the actual requirement for rapidly determining the aluminum content in the vaccine product on site, the sample preparation process is simple and convenient, the analysis speed is high, and the result is reliable. Therefore, the method has a wide practical application prospect and a remarkable popularization value.

Description

Technical Field

[0001] The present invention belongs to the field of detection technology and more specifically relates to a method for rapidly determining the content of aluminum adjuvant in vaccines. Background Art

[0002] Aluminum adjuvant is the most widely used adjuvant in human vaccines, among which the aluminum content has the most significant impact on the immunogenicity and safety of vaccines. On the one hand, aluminum adjuvant enhances the ability of vaccines to induce immune responses through mechanisms such as reservoir effect and immunostimulatory effect, playing a positive auxiliary role. On the other hand, aluminum can induce allergic reactions in the human body and has neurotoxicity, including local adverse reactions such as pain, nodules, swelling, and potential unsafe factors such as damage to the nervous system and macrophage myofasciitis. Therefore, the amount of aluminum adjuvant in the vaccine needs to take into account the auxiliary effect of the adjuvant and the potential safety hazards. At present, the aluminum adjuvant of vaccines that have been marketed worldwide is mostly 0.3-0.5 mg / dose. How to quickly and accurately determine the aluminum content in vaccines is the actual demand of manufacturers and inspection agencies.

[0003] At present, the determination of aluminum content in vaccines mainly includes complexometric titration, ultraviolet spectrophotometry, ICP-OES, ICP-MS, etc. These methods have disadvantages such as large sample consumption and slow analysis speed. Energy dispersive X-ray fluorescence spectroscopy (ED-XRF) does not require a precise motion device for the spectroscopic crystal and a light source cooling device. It has a simple structure, low requirements for sample preparation, and is easy to develop portable equipment. It is one of the important technical means for rapid on-site determination of elements. However, the fluorescence yield of low atomic number elements is low, the characteristic X-ray signal is weak, and it is easily submerged by the Compton scattering background of the primary radiation continuum. It is difficult to use traditional ED-XRF to analyze trace and trace light elements (elements with atomic numbers less than 20). Summary of the invention

[0004] The technical problem to be solved by the present invention is to overcome the defects and shortcomings of the prior art that there is a lack of a method for quickly and accurately determining the aluminum content in vaccines, and to provide a method for determining the aluminum content based on MED-XRF.

[0005] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0006] The present invention protects a method for determining the aluminum content in aluminum-containing vaccines based on MED-XRF, comprising the following steps:

[0007] S1. Using nitric acid solution as solvent to prepare the sample solution and standard solution;

[0008] S2. The standard solution obtained in step S1 is subjected to MED-XRF measurement to establish a standard curve equation of signal intensity and aluminum concentration;

[0009] S3. Perform MED-XRF measurement on the sample solution obtained in step S1 to obtain the signal intensity, substitute it into the standard curve equation obtained in step S2 to obtain the aluminum content in the sample solution;

[0010] Wherein, the MED-XRF measurement time is greater than 100 s.

[0011] This method uses monochromatic focusing-energy dispersive X-ray fluorescence spectroscopy (MED-XRF) to systematically study the preparation and testing conditions of heterogeneous liquid samples and establish an analytical method for rapid determination of aluminum content in vaccines. The results show that this method has the advantages of high accuracy, good precision and low detection limit, and can be used for on-site rapid determination of aluminum adjuvant content in vaccine products, which has broad practical promotion significance.

[0012] Preferably, the volume concentration of the nitric acid solution is 20-50%, more preferably 20%-40%, most preferably 30%.

[0013] Preferably, the thickness of the backing material measured by MED-XRF is 4 to 12 μm, more preferably 4 to 6 μm. A too thick film affects the signal intensity of characteristic X-rays, while a too thin film is prone to deformation and leakage.

[0014] Preferably, the MED-XRF measurement time is 200 to 600 seconds.

[0015] Furthermore, the method for preparing the test sample solution comprises the following steps: mixing the test sample with a nitric acid solution, and placing the mixture at 30 to 40° C. for 5 to 25 minutes to obtain the test sample solution.

[0016] Preferably, the volume ratio of the sample to be tested to the nitric acid solution is 1:(0.9-1.1), preferably 1:1.

[0017] Preferably, the excitation source of the MED-XRF measurement is X-rays.

[0018] Preferably, the target material for the MED-XRF measurement is Cr.

[0019] Preferably, the operating voltage of the MED-XRF measurement is 20-30 kV, more preferably 25 kV.

[0020] Preferably, the operating current of the MED-XRF measurement is 0.3-0.5 mA, more preferably 0.4 mA.

[0021] Preferably, the detector for the MED-XRF measurement is a silicon drift detector SDD.

[0022] Compared with the prior art, the present invention has the following beneficial effects: The present invention uses monochromatic focusing-energy dispersion X-ray fluorescence spectroscopy to systematically explore the preparation and testing conditions of heterogeneous liquid samples, and accordingly establishes an analytical method for rapid determination of aluminum content in vaccines. Compared with classical spectroscopy, this method exhibits significant superiority: the absolute value of its relative error is controlled within 10%, ensuring a high degree of accuracy and good precision, while having a low detection limit. This method fully meets the actual needs of on-site rapid determination of aluminum content in vaccine products. Not only is the sample preparation process simple, but the analysis speed is fast and the results are reliable. Therefore, this method has broad practical application prospects and significant promotion value. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The X-ray fluorescence spectra of the blank sample solution and the standard working solution in Example 1 are shown in FIG.

[0024] Figure 2 This is a comparison chart of the measurement results of Example 4 at different test times.

[0025] Figure 3 This is a comparison chart of the measurement results of different backing film thicknesses. DETAILED DESCRIPTION

[0026] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0027] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0028] Experimental equipment and materials

[0029] (1) Instruments and parameters

[0030] E-lite portable X-ray fluorescence spectrometer, the excitation source is an X-ray tube, the target material is Cr, the working voltage is 25kV, the working current is 0.4mA, and the test time is 300s.

[0031] ICAP PRO X DUO inductively coupled plasma optical emission spectrometer (Thermo Fisher, USA); ICAPRQ inductively coupled plasma mass spectrometer (Thermo Fisher, USA).

[0032] (2) Materials and reagents

[0033] Aluminum standard solution (National Iron and Steel Materials Testing Center, General Iron and Steel Research Institute, batch number: 22033135, concentration: 1000 μg / mL; medium: 10% HNO3 ), Scandium standard solution (National Iron and Steel Materials Testing Center, batch number: 22070435, concentration: 1000 μg / mL; medium: 10% HNO 3 ), nitric acid (super pure, Guangzhou Chemical Reagent Factory); phosphoric acid (analytical pure, Guangzhou Chemical Reagent Factory); hydrochloric acid (analytical pure, Guangzhou Chemical Reagent Factory); pure water (prepared by Milli-Q); polypropylene film (4.0μm, 12.0μm, Chemplex, USA); vaccine samples came from 5 domestic vaccine manufacturers, including 6 varieties, including new coronavirus inactivated vaccine (Vero cells), recombinant hepatitis E vaccine (Escherichia coli), bivalent human papillomavirus vaccine (Escherichia coli), recombinant hepatitis B vaccine (brewer's yeast), adsorbed acellular diphtheria and tetanus combined vaccine, and influenza virus split vaccine.

[0034] The MED-XRF method is a method that uses monochromatic focusing-energy dispersive X-ray fluorescence spectroscopy technology (such as the E-lite portable X-ray fluorescence spectrometer) to determine the content of a certain element.

[0035] ICP-OES method refers to the method of determining the content of a certain element using inductively coupled plasma emission spectrometer.

[0036] ICP-MS is a method that uses inductively coupled plasma mass spectrometry to determine the content of a certain element.

[0037] The present invention uses ICP-OES and ICP-MS as references to verify accuracy, and provides a method for quickly determining the aluminum content in aluminum-containing adjuvant vaccines based on the MED-XRF method.

[0038] The concentrations of different acids all refer to volume fraction concentrations.

[0039] Example 1 A method for rapidly determining the aluminum content in aluminum adjuvant vaccines based on MED-XRF

[0040] A method for rapidly determining the aluminum content in aluminum adjuvant vaccines based on MED-XRF, specifically comprising the following steps:

[0041] (1) Preparation of standard working solution

[0042] Accurately measure 0.25, 0.5, 1.0, 1.5, and 2.0 mL of 1000 μg / mL aluminum standard solution into 5 mL volumetric flasks, dilute and fix to the scale with negative vaccine matrix (influenza virus split vaccine) solution, and prepare a series of standard working solutions with aluminum concentrations of 50, 100, 200, 300, and 400 μg / mL.

[0043] (2) Drawing of standard curve

[0044] The standard working solution was measured according to the optimal parameters set by MED-XRF (E-lite portable X-ray fluorescence spectrometer). According to the basic parameter method, the original spectrum of the light tube and the detection efficiency of the detector were fitted with theoretical data (including element fitting, fluorescence yield, Compton and sharp scattering, escape peak, superposition peak, mass absorption coefficient and other parameters), and then the theoretical parameters were iteratively processed with a small amount of standard working solution until the linear regression equation of the measured content and the standard content was close to y=x. The standard curve was drawn and built into the XRF measurement software for actual sample detection. Among them, the working conditions of the MED-XRF test instrument are: the excitation source is an X-ray tube, the target material is Cr, the detector is a silicon drift detector SDD, the working voltage is 25kV, the working current is 0.4mA, the test time is 300s, and a 4μm polypropylene film is used as the backing material.

[0045] (3) Configuration of the sample to be tested

[0046] Preparation of the sample to be tested: Take 1.0 mL of the premixed vaccine sample in a centrifuge tube, add 1.0 mL of 30% nitric acid solution, vortex mix, place in a 40°C water bath for 25 minutes, take out and cool to room temperature, as the sample solution to be tested. The sample solution to be tested is loaded into the sample cup from the silicone valve of the set sample cup, and is placed in the MED-XRF instrument for measurement under the same test conditions as the standard curve, and the X-ray fluorescence intensity is obtained. The aluminum content in the sample is calculated using the built-in standard curve obtained in step (2).

[0047] Preparation of blank sample solution: add 1.0 mL of 30% nitric acid solution to 1.0 mL of vaccine without aluminum adjuvant, vortex mix, place in a 40°C water bath for 25 min, take out and cool to room temperature to obtain a blank sample solution.

[0048] The X-ray fluorescence spectra of the blank sample solution (sample matrix) obtained in step (3) and the standard working solution obtained in step (1) are as follows: Figure 1 The Kα1 characteristic line energy peak of aluminum is 1.49 keV. The integration and fitting are performed in the energy range of 1.49±0.1 keV. It can be seen that the higher the aluminum content concentration in the standard working solution, the stronger the Kα1 characteristic line energy peak of aluminum.

[0049] Example 2 Selection of pretreatment reagents

[0050] Referring to the method for determining the aluminum content in aluminum adjuvant vaccines by the MED-XRF method in Example 1, this example investigates the effects of different pretreatment reagents (phosphoric acid, hydrochloric acid, water, nitric acid) on the detection of aluminum content, as follows:

[0051] The specific experimental steps for using nitric acid as a pretreatment reagent are as follows: take 1.0 mL of the premixed vaccine sample (new coronavirus inactivated vaccine (Vero cells), reference value is 0.50 mg / mL, the same below) into a centrifuge tube, add 1.0 mL of 30% nitric acid solution, vortex to mix, place in a 40°C water bath for 25 minutes, take out and cool to room temperature as the sample solution to be tested.

[0052] The specific experimental steps of using hydrochloric acid as the pretreatment reagent are as follows: take 1.0 mL of the premixed vaccine sample into a centrifuge tube, add 1.0 mL of 50% hydrochloric acid solution, vortex mix, place in a 40°C water bath for 25 minutes, take out and cool to room temperature as the sample solution to be tested.

[0053] The specific experimental steps of using water as the pretreatment reagent are as follows: take 1.0 mL of the premixed vaccine sample into a centrifuge tube, add 1.0 mL of water, vortex mix, place in a 40°C water bath for 25 min, take out and cool to room temperature as the sample solution to be tested.

[0054] The specific experimental steps of using phosphoric acid as a pretreatment reagent are as follows: take 1.0 mL of the premixed vaccine sample into a centrifuge tube, add 1.0 mL of 6% phosphoric acid solution, vortex mix, heat in a boiling water bath for 20 minutes to completely dissolve, take out and cool to room temperature as the sample solution to be tested.

[0055] The results are shown in Tables 1 to 4.

[0056] Table 1 Determination results of aluminum content in nitric acid as pretreatment reagent

[0057]

[0058] Table 2 Determination results of aluminum content using hydrochloric acid as pretreatment reagent

[0059]

[0060]

[0061] Table 3 Determination results of aluminum content in water as pretreatment reagent

[0062]

[0063] Table 4 Determination results of aluminum content in phosphoric acid as pretreatment reagent

[0064]

[0065] The results show that phosphoric acid is the pretreatment reagent selected for the determination of aluminum content in the third volume of the Chinese Pharmacopoeia. For vaccines with different adsorption types, the phosphoric acid treatment method has great differences in acid concentration, pretreatment time, pretreatment temperature, etc., and some varieties need to be boiled to achieve aluminum desorption, and the experimental conditions are relatively harsh. For example, it is necessary to heat the sample solution in a boiling water bath for more than 20 minutes to present a uniform and clear state, and to achieve complete desorption of aluminum, and there are large errors in the determination results (Table 4).

[0066] When hydrochloric acid is used as a pretreatment reagent, it is more commonly used in ICP-OES testing. However, in the MED-XRF test, it was found that the aluminum content of the sample pretreated with hydrochloric acid solution was higher. This is mainly because compared with water and nitric acid, the scattering intensity of hydrochloric acid to primary radiation is very different, resulting in the analysis background far exceeding the range of mathematical correction. As shown in Table 2, the aluminum content result is too high.

[0067] When water was used as the pretreatment reagent, it only dispersed and diluted the vaccine sample, but did not destroy the adsorption of aluminum adjuvant and antigen. The sample treatment solution was still in a suspended state, resulting in significantly lower measurement results (Table 3).

[0068] When nitric acid is used as the pretreatment reagent, the background interference is small. After pretreatment at 40°C for 25 minutes, the aluminum adjuvant and the antigen in the sample can be fully dissociated, the sample treatment liquid is uniformly clarified, and the experimental conditions are mild, and the measurement results are relatively accurate (Table 1). Therefore, the present invention uses nitric acid as the pretreatment reagent.

[0069] Example 3 Optimization of pretreatment conditions

[0070] Referring to the method for determining the aluminum content in aluminum adjuvant vaccines by MED-XRF method in Example 1, the effects of nitric acid concentration, reaction time and reaction temperature on the detection of aluminum content were investigated, as follows:

[0071] In this embodiment, a single factor test is performed on the main factor nitric acid concentration, and the influence of nitric acid concentration of 2%, 5%, 10%, 20%, 30%, 50%, 80%, and 100% on the determination of an actual sample (recombinant hepatitis B vaccine (brewer's yeast), with a reference value of 0.45 mg / mL) is compared. The results are shown in Table 5. When the nitric acid concentration is between 2% and 100%, the relative error of the determination result is within 10%. As the nitric acid concentration increases, the detection result and RSD show a downward trend. When the nitric acid concentration is 20%, 30%, and 50%, the absolute value of the relative error is less than 5%, and the RSD is not greater than 2%. The measurement accuracy and precision are good.

[0072] Based on the single factor experiment, a three-factor three-level orthogonal experiment L9 (3 4), with accuracy as the evaluation index, the pretreatment conditions were optimized. The test factors, levels and results are shown in Table 6. Through intuitive analysis of the results, it can be seen that the nitric acid concentration has the greatest impact on the results. A nitric acid concentration of 30% and a treatment of 40°C for 25 minutes are good pretreatment conditions.

[0073] Table 5 Effect of nitric acid concentration on aluminum content determination

[0074]

[0075] Table 6 Orthogonal experimental scheme and intuitive analysis table

[0076]

[0077]

[0078] Example 4 Confirmation of test time

[0079] Referring to the method for determining the aluminum content in aluminum adjuvant vaccines by MED-XRF in Example 1, the effect of MED-XRF measurement time on the detection of aluminum content was investigated, as follows:

[0080] Since there is no linear relationship between the measurement time of MED-XRF and the test count rate of the sample, different test times have a significant impact on the stability and accuracy of the results. The present invention investigates the repeatability of the results of six parallel tests of a 250 μg / mL aluminum standard solution at test times of 30, 60, 100, 200, 300, and 600 s.

[0081] The experimental results are shown in Figure 2 When the test time is 30-100s, the RSD (relative standard deviation) of the measurement result is large and the repeatability is poor; when the test time is greater than 100s, the measurement result is close to the actual theoretical value, the distribution of each measurement result is concentrated, the reproducibility is good, and there is no significant difference in the measurement results of 200, 300, and 600s. Taking into account both the test accuracy and the test efficiency, the subsequent test time is 300s.

[0082] Example 5 Confirmation of the thickness of the back cover film

[0083] Referring to the method for determining the aluminum content in aluminum adjuvant vaccines by MED-XRF method in Example 1, the effect of polypropylene films of different film thicknesses on the detection of aluminum content was investigated, as follows:

[0084] In this study, the effect of polypropylene films with different film thicknesses on the intensity of aluminum characteristic fluorescence lines was compared using a standard solution with a concentration of 400 μg / mL. Figure 3As shown in the figure, the 12μm-thick film has a certain influence on the signal strength of the aluminum element analysis line, and the measurement repeatability is slightly poor, while the 4μm-thick film has better measurement repeatability. In order to improve the strength of the analysis line and take into account the leak-proof ability, the subsequent study uses 4μm polypropylene film as the backing material.

[0085] Example 6 Methodological Investigation

[0086] This example further tests the effect of the method in Example 1.

[0087] (1) Limit of detection and limit of quantification

[0088] In this paper, the repeated determination method is used to determine the detection limit and quantification limit of the method, that is, the low-content sample solution is repeatedly measured 11 times under the same experimental conditions (the conditions of Example 1), and 3 times the standard deviation of the measured value is used as the detection limit, and 10 times the standard deviation is used as the quantification limit. The results are shown in Table 7. The detection limit of aluminum determined by the method of Example 1 is 0.027 mg / mL, and the quantification limit is 0.090 mg / mL.

[0089] (2) Recovery rate and repeatability

[0090] The vaccine samples without aluminum adjuvant were subjected to spike recovery test at three levels of 0.3 mg / mL, 0.5 mg / mL and 0.7 mg / mL, and 6 samples were prepared for each level. The results are shown in Table 7. The results showed that within the spike level, the average recovery rate was 97.6% to 102%, the precision RSD (n=6) was 2.4% to 6.7%, and the recovery rate and repeatability were good.

[0091] Table 7 Detection limit, quantification limit, recovery and repeatability of the method

[0092]

[0093] (3) Inter-day precision

[0094] MED-XRF quantitative analysis adopts a standard-free analysis method, and the stability of the instrument measurement is very important to the result. The present invention performs multiple measurements on actual samples (recombinant hepatitis E vaccine (Escherichia coli), the reference value is 0.54 mg / mL) within 90 days, and the results are shown in Table 8. The results show that the coefficient of variation of multiple measurements of the same sample within 90 days is 4.7%, and the data is concentrated, and the method is stable and reliable.

[0095] Table 8 Inter-day precision of the method

[0096]

[0097]

[0098] (4) Measurement and accuracy of actual samples

[0099] The present invention uses the ICP-OES method (for specific equipment measurement parameters, see CN117607239A) and the ICP-MS method (for specific equipment measurement parameters, see Liu Congcong, Lin Yuanheng, Yin Yanxiang, et al. Comparison of ICP-MS and ICP-OES methods for determining aluminum content in vaccines [J]. Chinese Pharmaceutical Standards, 2024, 25(05): 471-477. DOI: 10.19778 / j.chp.2024.05.007.) as references to verify the accuracy of the MED-XRF method in Example 1.

[0100] ICP-OES method: Accurately measure an appropriate amount of aluminum standard solution, and dilute it step by step with 0.1mol / L hydrochloric acid solution to prepare a series of standard solutions with a concentration of 1-20μg / mL. Accurately measure 0.2mL of vaccine sample and place it in a plastic centrifuge tube, add 0.2mL of 5mol / L hydrochloric acid solution, and place it at room temperature for 0.5h. After the sample is completely dissolved and the solution is clear, add water to 10mL to obtain the sample solution to be tested. The series of standard solutions and the sample solution to be tested are measured by ICP-OES (ICAP PRO X DUO inductively coupled plasma emission spectrometer), and the aluminum content in the sample is calculated by the standard curve.

[0101] ICP-MS method: Accurately measure an appropriate amount of aluminum standard solution, and dilute it step by step with 5% nitric acid solution to prepare a series of standard solutions with concentrations of 2.5 to 80 ng / mL. A 50 ng / mL scandium single element standard solution prepared with 5% nitric acid solution is used as the internal standard solution. Accurately measure 0.05 mL of the vaccine sample and place it in a plastic centrifuge tube, add 5 mL of nitric acid, vortex mix, and place it at room temperature for 0.5 h. Then take 0.05 mL of the above solution and dilute it to 10 mL with 5% nitric acid to obtain the sample solution to be tested. The series of standard solutions and the sample solution to be tested are determined by ICP-MS (ICAP RQ inductively coupled plasma mass spectrometer) using the internal standard method, and the aluminum content in the sample is calculated using the standard curve.

[0102] The results of ICP-OES and ICP-MS were tested for significance (t-test method), and samples with no significant difference between the two results (t 0.1，4 <2.13) as the representative, and the average of the results of the two methods is used as the reference value to examine the accuracy of the MED-XRF method. As can be seen from Table 9, the MED-XRF method has good consistency with the reference value for the determination results of 70 batches of vaccines of 6 varieties, and the absolute value of the relative error does not exceed 10%, which meets the requirements of rapid quantitative analysis of aluminum content in different vaccines.

[0103] Table 9 Actual sample results and relative accuracy

[0104]

[0105]

[0106]

[0107]

[0108]

[0109]

[0110] Note: ND means not detected.

[0111] The present invention systematically studies the preparation and testing conditions of heterogeneous liquid samples, adopts the monochromatic focusing technology of hyperbolic curved crystals, and uses the fundamental parameter method to correct the matrix effect, thereby solving the problem of low sensitivity of energy dispersive X-ray fluorescence spectroscopy technology to aluminum element detection. The results show that the measured values ​​and theoretical values ​​of aluminum elements in different types of vaccine matrices are significantly positively correlated, the correlation coefficients of the fitting equations are all greater than 0.998, and the detection limit and quantification limit are 0.027 mg / mL and 0.090 mg / mL, respectively. Within the 0.3 mg / mL to 0.7 mg / mL spiked level, the average recovery rate is 97.6% to 102%, and the precision RSD (n=6) is 2.4% to 6.7%. The daytime precision of the same sample within 90 days is 4.7%. Compared with the classical spectroscopy method, the absolute value of the relative error is not more than 10%, which meets the technical requirements for on-site rapid determination of aluminum content in vaccine products, and has the advantages of simple sample preparation, fast analysis speed, and reliable results.

[0112] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for determining the aluminum content in aluminum-containing vaccines based on MED-XRF, characterized in that: The following steps are involved: S1. Using nitric acid solution as solvent to prepare the sample solution and standard solution; S2. The standard solution obtained in step S1 is subjected to MED-XRF measurement to establish a standard curve equation of signal intensity and aluminum concentration; S3. Perform MED-XRF measurement on the sample solution obtained in step S1 to obtain the signal intensity, substitute it into the standard curve equation obtained in step S2 to obtain the aluminum content in the sample solution; Wherein, the MED-XRF measurement time is greater than 100 s.

2. The method according to claim 1, characterized in that: The volume concentration of the nitric acid solution is 20-50%.

3. The method according to claim 1, characterized in that: The thickness of the backing material measured by MED-XRF is 4-12 μm.

4. The method according to claim 1, characterized in that: The MED-XRF measurement time is 200 to 600 seconds.

5. The method according to claim 1, characterized in that: The method for preparing the sample solution to be tested comprises the following steps: mixing the sample to be tested with a nitric acid solution, and placing the mixture at 30 to 40° C. for 5 to 25 minutes to obtain the sample solution to be tested.

6. The method according to claim 1, characterized in that: The volume ratio of the sample to be tested to the nitric acid solution is 1:(0.9-1.1).

7. The method according to claim 1, characterized in that: The excitation source of the MED-XRF measurement is X-ray.

8. The method according to claim 1, characterized in that: The target material for the MED-XRF measurement is Cr.

9. The method according to claim 1, characterized in that: The working voltage of the MED-XRF measurement is 20 to 30 kV.

10. The method according to claim 1, characterized in that: The working current of the MED-XRF measurement is 0.3-0.5 mA.

Images