A method for separating and purifying indium from a cadmium-indium mixture

Abstract

This invention discloses a method for separating and purifying indium from a cadmium-indium mixture. The method involves dissolving and filtering the substance to be purified, containing both cadmium and indium compounds, to obtain a mixed solution. Separation is then performed in a chromatograph using a high-efficiency cation exchange packing as the stationary phase and an aqueous solution of an organic acid as the mobile phase. The indium solution is collected based on the indium peak time. The high-efficiency cation exchange packing is a silica gel packing with sulfonic acid groups bonded to its surface; the organic acid is at least one selected from oxalic acid, citric acid, and α-hydroxyisobutyric acid, with a concentration of 10-400 mM and a pH of 2.0-5.5. This method achieves a maximum separation degree of 24.94, can separate indium purity of over 99.8% in a single step, has an analysis time of less than 35 minutes, and exhibits good scalability, meeting the production requirements of the medical isotope indium-111.

Description

Technical Field

[0001] This invention relates to the field of metal element separation and purification, and specifically to a method for separating and purifying trace amounts of indium from a cadmium-indium mixture. Background Technology

[0002] Radioactive isotope indium-111 ( 111 Indium (In) is the most clinically mature medical isotope for indium. In recent years, based on... 111 Single-photon emission computed tomography (SPECT) using In-labeled tracers enables highly sensitive imaging and shows great potential for clinical applications in areas such as disease diagnosis and intraoperative navigation, for example, " 111 Inpanitumab can be used to diagnose lymph node metastasis in prostate cancer; 111 In-labeled imaging agents, combined with fluorescence imaging, can illuminate tumor boundaries and metastatic lymph nodes in real time during head and neck cancer surgery, helping doctors to remove tumors more thoroughly.

[0003] Currently, medical isotopes 111 There are two main methods for producing indium (In). One method involves irradiating natural or enriched cadmium with protons or deuterons; the other involves irradiating silver with alpha rays or irradiating tin with protons. Compared to using silver or tin as the target material, the preparation of indium using cadmium as the target material is more efficient. 111 In yields are generally high. However, the production of in is achieved by proton or deuterium irradiation of natural or enriched cadmium. 111 In also faces significant challenges. This is because natural cadmium is composed of multiple stable isotopes, such as... 111 Cd (12.80%) 112 Cd (24.13%) 113 Cd (12.22%) and 114 Therefore, irradiation of natural cadmium with protons or deuterons will produce Cd (28.73%), etc. 111 In and other radioactive isotopes of indium ( 114m In、 115m In、 110m In、 109m (In, etc.). Indium-114, in particular, has a long half-life of 49.5 days, which may interfere with imaging and increase patient radiation dose in clinical applications. Furthermore, when protons bombard cadmium targets, only one part per hundred thousand to one part per million of cadmium is converted to indium; therefore, a large amount of cadmium remains in the irradiation products. For these reasons, how to effectively manage trace amounts of radioactivity... 111 In, through the isolation and purification of large quantities of cadmium targets, isotopes suitable for medical use were extracted. 111 The production of In is crucial.

[0004] Used for separation and purification 111Common techniques for indium adsorption include ion exchange chromatography, solvent extraction, and coprecipitation. Ion exchange chromatography, in particular, utilizes the difference in adsorption capacity between indium and target ions on a resin. 111 The separation of In is currently the most advanced method for separation and purification. 111 One of the mainstream methods for separating indium is ion exchange chromatography. However, current ion exchange chromatography methods generally use large-particle resin packing materials (particle size ≥ 50 μm) as the separation medium, which has problems such as low separation efficiency, poor reproducibility of separation results, and short packing material life, making it unfavorable for the efficient and high-quality separation of cadmium and indium. Especially for applications that separate and purify trace amounts of indium from large amounts of cadmium, it is difficult to achieve rapid and efficient separation of high-purity indium using large-particle resin packing materials. For example, the literature (https: / / doi.org / 10.2478 / s11532-010-0041-z) uses Dowex 50W-X8 cation exchange resin with a particle size of 50 micrometers as the separation material and inorganic acid as the eluent to separate cadmium and indium, but the separation effect is poor, and baseline separation of cadmium and indium cannot be achieved. Patent US6162648A describes using Dowex 1X8-200 anion exchange resin with a particle size of 100 micrometers as the separation material and inorganic acid as the eluent to separate cadmium and indium, but the method involved in this patent has a very small sample throughput, and the packing material cannot be recycled, making industrial-scale production impossible. This paper addresses the above-mentioned methods for enriching and purifying trace amounts of cadmium from large quantities of cadmium target materials. 111 Given the numerous challenges faced by In, exploring a rapid and efficient Cd / In separation method is crucial for the development of medical isotopes. 111 In's production and based 111 The widespread adoption of SPECT scanning technology in the United States is of great significance. Summary of the Invention

[0005] For trace amounts of cadmium targets after proton accelerator bombardment 111 To address the problem of separating and purifying trace amounts of indium, this invention provides a method for separating and purifying trace amounts of indium from a cadmium-indium mixture using high-performance ion exchange chromatography. 111 A highly efficient method for the separation and purification of In was developed, achieving the separation of In under specific mobile phase, pH value, and concentration. 3+ and Cd 2+ Optimal chromatographic separation and purification conditions were achieved for In 3+ and Cd 2+ This highly efficient separation and purification method effectively solves the problem of high-purity medical isotopes. 111 The rapid purification of In, particularly in high-purity medical isotopes. 111 In provides important support for the production and mass supply of In, and also provides new research ideas for the separation and purification of other high-purity medical isotopes.

[0006] To achieve the objectives of this invention, the technical solution adopted is as follows:

[0007] A method for separating and purifying indium from a cadmium-indium mixture includes the following steps: dissolving and filtering the substance to be purified to obtain a mixed solution containing cadmium and indium, wherein the substance to be purified comprises a mixture of cadmium compounds and indium compounds; eluting and separating the indium using a chromatographic column with an average particle size of no more than 5 μm as the stationary phase and an aqueous solution of organic acid as the mobile phase; collecting the indium solution from the detector of the chromatograph according to the indium peak time; and collecting the indium-containing fraction to obtain high-purity indium.

[0008] Preferably, the cadmium- and indium-containing mixed solution to be purified is a solution obtained by dissolving a mixture containing cadmium and indium metals or their compounds, formed after irradiating a cadmium target.

[0009] Preferably, the mass ratio of cadmium to indium in the mixed solution to be purified is ≥1000:1, and the chemical purity of indium is greater than 99.8% after one separation.

[0010] Preferably, the cadmium target is one of elemental cadmium, cadmium oxide, cadmium chloride, cadmium nitrate, or cadmium sulfate.

[0011] Preferably, the high-efficiency cation exchange packing is a silica gel surface polar group bonded phase packing, and its ion exchange functional group is a sulfonic acid group. It should be noted that the packing preparation method and performance in this invention are consistent with those described in patent CN202211208075.X, and will not be repeated here.

[0012] Preferably, the mobile phase is a mixed solution of organic acid and water.

[0013] Preferably, the organic acid is one of oxalic acid, citric acid, α-hydroxyisobutyric acid (HIBA), or 2-hydroxy-2-methylbutyric acid.

[0014] Preferably, the concentration of the organic acid in the mobile phase is 10~400 mM.

[0015] Preferably, the pH of the mobile phase is 2.0 to 5.5, and the flow rate is 0.20 to 40 mL / min.

[0016] Preferably, the elution conditions are isocratic elution or gradient elution, and the column temperature is 10~60℃.

[0017] Beneficial effects:

[0018] Compared with existing technologies, this invention provides a method for separating and purifying trace amounts of indium from a cadmium-indium mixture. It offers a rapid, efficient, and simple method for cadmium / indium separation and purification, effectively solving the technical challenge of enriching and purifying trace amounts of indium-111 from large quantities of cadmium targets. This provides crucial technical support for the production and mass supply of high-purity medical isotope indium-111, and also offers new research ideas and technical references for the separation and purification of other high-purity medical isotopes. It has the following advantages:

[0019] 1. Breakthrough Improvement in Separation Efficiency: This invention is the first to apply high-efficiency cation exchange packing material with an average particle size ≤5 μm to the cadmium-indium separation system, replacing the ≥50 μm large-particle resin packing material commonly used in existing technologies. Due to the significant reduction in packing particle size, the column efficiency is greatly improved, resulting in a resolution (R) of up to 24.94 for cadmium and indium (see Example 1), far exceeding the baseline separation requirement (R≥1.5). Compared with the inability to achieve baseline separation in existing technologies, this invention achieves complete separation of cadmium and indium, laying a technical foundation for the acquisition of high-purity indium.

[0020] 2. Significantly Improved Product Purity: Using the method of this invention, only one or two chromatographic separation processes are required to obtain an indium solution with a chemical purity higher than 99.8% from a mixture containing a large amount of cadmium (cadmium-indium mass ratio as high as 1000:1) (see Example 3). This purity level can meet the stringent requirements for the production of medical isotope indium-111, solving the technical bottleneck of existing technologies in obtaining high-purity indium.

[0021] 3. Fast analysis speed and short process flow: The method described in this invention can complete a separation and purification process within 35 minutes (see Example 1), featuring rapid analysis. Compared with the time-consuming separation process in the prior art, this invention significantly shortens the production cycle and improves production efficiency;

[0022] 4. Excellent separation selectivity and strong anti-interference ability: The organic acid mobile phase system optimized and screened by this invention (especially α-hydroxyisobutyric acid) exhibits excellent separation selectivity and strong anti-interference ability for In... 3+ and Cd 2+ It exhibits excellent selectivity, with a selectivity factor α reaching up to 7.74 (see Example 1). Even in the presence of other metallic impurities (such as Fe), 3+ Cu 2+ Even under these conditions, the target indium ions can still be well separated (see Example 4), indicating that the method has good anti-interference ability and is suitable for the separation of trace indium in complex systems;

[0023] 5. Strong scalability and industrial production potential: The high-performance liquid chromatography (HPLC) technology used in this invention has excellent scalability. Depending on the required sample throughput, the separation and purification of samples from milligram to hundred-gram scales can be achieved by flexibly adjusting the column size, without loss of separation efficiency due to increased throughput. This characteristic overcomes the shortcomings of existing technologies (such as US6162648A) that cannot achieve industrial-scale production, providing a feasible technical path for the large-scale production and supply of the medical isotope indium-111.

[0024] 6. The entire separation process is simple to operate, has good reproducibility, low cost, and is easy to promote and apply. Attached Figure Description

[0025] Figure 1 This is the chromatogram of cadmium and indium ions separated in Example 1;

[0026] Figure 2 This is the chromatogram of cadmium and indium ions separated in Example 2;

[0027] Figure 3 This is the chromatogram of cadmium and indium ions separated in Example 3;

[0028] Figure 4 This is a chromatogram of the separation of cadmium and indium ions in Example 4. Detailed Implementation

[0029] To make the objectives, features, and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention are described in detail below with reference to the examples. Several embodiments of the present invention are given in the examples. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that the disclosure of the present invention will be more thorough and complete.

[0030] This invention provides embodiments for the preparation of medical isotopes based on proton accelerator bombardment of natural or enriched cadmium. 111 During the indium extraction process, only one ten-thousandth to one millionth of cadmium is converted into indium, and the products contain a large amount of other radioactive indium isotopes. Therefore, the challenge lies in achieving low-cost, efficient extraction of indium from sources containing trace amounts of medical isotopes. 111 In cadmium target material separation and purification 111 In is a problem that urgently needs to be solved.

[0031] This invention employs high-efficiency ion-exchange chromatography, using a strong cation-exchange column and an aqueous solution of organic acid as the mobile phase. By optimizing the pH, concentration, and type of the mobile phase, indium can be separated and purified from a mixture containing a large amount of cadmium and a small amount of indium. The chromatographic separation process in this invention is simple, rapid, efficient, and inexpensive.

[0032] The following will describe the content of the present invention and the positive effects brought about by the present invention through specific implementation methods.

[0033] Example 1

[0034] A method for separating and purifying trace amounts of indium from a cadmium-indium mixture, based on a strong cation exchange column, using high-performance liquid chromatography (HPLC), includes the following steps:

[0035] A. Solution preparation

[0036] Accurately weigh 0.1927 g of anhydrous indium chloride (InCl3, analytical grade, molar mass 221.18 g / mol) into a 50 mL beaker, add 20 mL of ultrapure water to dissolve it, and quantitatively transfer the solution to a 100 mL volumetric flask. Wash the beaker three times with ultrapure water, and add the washings to the volumetric flask. Finally, dilute to the mark with ultrapure water and mix well. This solution contains In... 3+ The concentration is 10000 mg / L.

[0037] Accurately weigh 0.1631 g of anhydrous cadmium chloride (CdCl2, analytical grade, molar mass 183.32 g / mol), and prepare a 10000 mg / L CdCl2 solution using the same method described above. 2+ Standard solution.

[0038] Transfer 1.0 mL each of 10000 mg / L indium standard solution and 10000 mg / L cadmium standard solution into 10 mL volumetric flasks, dilute to the mark with ultrapure water, and mix well to obtain the In-containing solution. 3+ and Cd 2+ A mixed solution of 1000 mg / L each. Then transfer 5.0 mL of this solution to a 10 mL volumetric flask, dilute to the mark with ultrapure water, and mix well to obtain the In-containing solution. 3+ and Cd 2+ A mixed solution of cadmium and indium at a concentration of 500 mg / L each.

[0039] It should be noted that the cadmium and indium solutions of different concentrations used in subsequent examples were all prepared using the above-mentioned standard solutions.

[0040] B. Preparation of the mobile phase

[0041] Mobile phase a: Weigh 20.8 g of HIBA, dissolve it in ultrapure water and put it into a 1 L volumetric flask. Make up to 1 L with ultrapure water and then put the solution into a mobile phase bottle. Measure its pH with a pH meter and it is 2.1. Add an appropriate amount of 13.4 M ammonia water and adjust the pH to 4.1 for later use.

[0042] Mobile phase b: Similarly, dissolve 42.028 g of citric acid and bring the volume to 1 L, then adjust the pH to 3.7 for later use;

[0043] Mobile phase c: Similarly, dissolve 18.006 g of oxalic acid to a final volume of 1 L, and adjust its pH to 3.5 for later use.

[0044] C. Ion exchange chromatography for the separation and purification of indium

[0045] The cadmium-indium mixed solution was separated using HIBA, citric acid, and oxalic acid aqueous solutions as mobile phases, respectively. The chromatograms are shown below. Figure 1 As shown.

[0046] The ion chromatography separation conditions used are as follows.

[0047] Column temperature: 25 ℃;

[0048] Flow rate: 1 mL min -1 ;

[0049] Column size: 250 mm * 4.6 mm (ID);

[0050] Filler particle size: 5 μm;

[0051] Injection volume: 10 μL;

[0052] Mobile phase a: HIBA-water (v / v=70:30) solution (200 mM) with a pH of 4.1;

[0053] Mobile phase b: Citric acid-water (v / v=30:70) solution (200 mM) with a pH of 3.7;

[0054] Mobile phase c: oxalic acid-water (v / v=50:50) solution (200 mM) with a pH of 3.5.

[0055] The parameters under the above three mobile phase conditions are shown in Table 1:

[0056] Table 1 Comparison of chromatographic separation parameters under three mobile phase conditions

[0057]

[0058] As can be seen from the data in Table 1, this invention, through the separation of a standard cadmium-indium mixed solution (1:1) under three different organic acid mobile phase systems, confirms the effectiveness of the high-efficiency cation exchange chromatography packing material for the separation of In... 3+ and Cd 2+It exhibits excellent separation selectivity, with a resolution of up to 24.94 and a selectivity factor of up to 7.74. The HIBA mobile phase system demonstrated the best separation performance, providing the basic separation conditions for subsequent simulations of actual production conditions in Examples 2-4. Furthermore, the chromatographic parameter system established in Example 1 provides a quantitative benchmark for evaluating the separation effect of the method of this invention.

[0059] Example 2

[0060] A high-performance liquid chromatography method based on a strong cation exchange column, simulating 112 Cd(p, x) 111 In the production line 111 The separation and purification of In includes the following steps:

[0061] The cadmium and indium solution prepared in Example 1 was diluted to prepare a simulated solution. 112 Cd(p, x) 111 Simulated mixed solution of cadmium-indium mixture obtained from the production line (m Cd : m In =1000:1), and then using mobile phase a and mobile phase b from Example 1 as mobile phases to separate the simulated mixed solution, the chromatogram of the separation results is shown in Figure 1. Figure 2 As shown.

[0062] The ion chromatography separation conditions used are as follows.

[0063] Column temperature: 25 ℃;

[0064] Flow rate: 1 mL min -1 ;

[0065] Column size: 250 mm * 4.6 mm (ID);

[0066] Filler particle size: 5 μm;

[0067] Injection volume: 10 μL;

[0068] Mobile phase a: HIBA-water (v / v=70:30) solution (200 mM) with a pH of 4.1;

[0069] Mobile phase b: Citric acid-water (v / v=30:70) solution (200 mM) with a pH of 3.7.

[0070] from Figure 2It can be seen that under both mobile phase conditions, the cadmium and indium peaks were well separated, with symmetrical peak shapes and no overlap. This indicates that the method of the present invention still has good separation capability under extreme conditions with a cadmium-indium mass ratio as high as 1000:1, and can meet the practical needs of separating trace indium from a large amount of cadmium target material.

[0071] Example 3

[0072] A high-performance liquid chromatography method based on a strong cation exchange column, simulating 112 Cd(p, x) 111 In the production line 111 The separation and purification of In includes the following steps:

[0073] The cadmium and indium solution prepared in Example 1 was diluted to prepare a simulated solution. 112 Cd(p, x) 111 Simulated mixed solution of cadmium-indium mixture obtained from the production line (m Cd : m In =1000:1), then a gradient elution was performed using a mixture of HIBA aqueous solution (200 mM) with a pH of 4.1 and pure water as the mobile phase relative to the simulated mixed solution. The chromatogram of the separation results is shown in the figure. Figure 3 As shown.

[0074] The ion chromatography separation conditions used are as follows.

[0075] Column temperature: 25 ℃;

[0076] Flow rate: 1 mL min -1 ;

[0077] Column size: 250 mm * 4.6 mm (ID);

[0078] Filler particle size: 5 μm;

[0079] Injection volume: 10 μL;

[0080] Mobile phase: a mixture of HIBA aqueous solution (200 mM) with pH 4.1 and pure water.

[0081] The gradient elution conditions are shown in Table 2, where the 5-8 min period is a linear gradient change, and the HIBA ratio increases uniformly from 70% to 90%.

[0082] Table 2 Gradient elution conditions

[0083]

[0084] The fraction containing indium ions was collected based on the elution time of indium ions in the chromatogram (collection interval 2.7-3.7 min), and then the purity of the sample was tested using ICP-OES. The test results are shown in Table 3.

[0085] Table 3. Test results of metal ion content in indium-containing fractions

[0086]

[0087] In this embodiment, under simulated actual production conditions (m_Cd : m_In = 1000:1), the indium ion fraction obtained by gradient elution was analyzed by ICP-OES and the indium ion chemical purity was 99.87%, indicating that the method of the present invention can efficiently separate high-purity indium from a high-concentration cadmium background, meeting the purity requirements for the production of medical isotope indium-111.

[0088] Example 4

[0089] A high-performance liquid chromatography method based on a strong cation exchange column, simulating 112 Cd(p, x) 111 When other trace metals are present in the production line 111 The separation and purification of In includes the following steps:

[0090] A. Preparation of other trace metal solutions

[0091] Due to actual production, 112 Cd targets may contain trace amounts of copper and iron impurities. Therefore, this embodiment simulates the effect of trace metal impurities in the target on... 111 The separation and purification effect of In. Weigh 0.2896 g of ferric chloride and 0.3805 g of copper chloride into centrifuge tubes, add ultrapure water to 10 mL to obtain two solutions of 10000 ppm, and then dilute them to 1000 ppm respectively.

[0092] B. Preparation of solutions in the simulation circuit

[0093] Formulating a mixture containing impurities Fe 3+ and Cu 2+ A mixed solution of cadmium and indium (100,000 ppm cadmium chloride, 1 ppm indium chloride, 1 ppm ferric chloride, 1 ppm copper chloride) was injected, and HIBA-water (70:30) with a pH of 4.1 was used as the mobile phase to separate the mixed solution of cadmium and indium chloride. The results are as follows: Figure 4 As shown.

[0094] The ion chromatography separation conditions used are as follows.

[0095] Column temperature: 25 ℃;

[0096] Flow rate: 1 mL min -1 ;

[0097] Column size: 250 mm * 4.6 mm (ID);

[0098] Filler particle size: 5μm;

[0099] Injection volume: 10 μL;

[0100] Mobile phase: HIBA-water (70:30) solution (200 mM) with pH 4.1.

[0101] from Figure 4 It can be seen that, In 3+ Cd 2+ Fe 3+ and Cu 2+ The chromatographic peaks were all well separated, with no significant overlap between them. Specifically, In... 3+ The elution time was approximately 3.6 min, which is basically consistent with the retention time in Example 1 when no impurities were present. This result indicates that Fe 3+ and Cu + The existence of In 3+ The separation of complex samples is significantly interfered with, but the method of this invention still has good separation selectivity in complex sample systems.

Claims

1. A method for separating and purifying indium from a cadmium-indium mixture, characterized in that, The substance to be purified is dissolved and filtered to obtain a mixed solution containing cadmium and indium. The substance to be purified is a mixture of cadmium compounds and indium compounds. The solution is eluted and separated by a chromatographic column with a high-efficiency cation exchange packing material with an average particle size of no more than 5 μm as the stationary phase and an aqueous solution of organic acid as the mobile phase. The indium solution exiting the detector of the chromatograph is collected according to the indium peak time. The indium-containing fraction is collected to obtain high-purity indium.

2. The method for separating and purifying indium from a cadmium-indium mixture according to claim 1, characterized in that, The cadmium- and indium-containing mixed solution to be purified is obtained by dissolving a mixture containing cadmium and indium metals or their compounds, formed after irradiating a cadmium target.

3. The method for separating and purifying indium from a cadmium-indium mixture according to claim 2, characterized in that, The mass ratio of cadmium to indium in the mixed solution to be purified is ≥1000:1, and the chemical purity of indium is greater than 99.8% after one separation.

4. The method for separating and purifying indium from a cadmium-indium mixture according to claim 2, characterized in that, The cadmium target is one of elemental cadmium, cadmium oxide, cadmium chloride, cadmium nitrate, or cadmium sulfate.

5. The method for separating and purifying indium from a cadmium-indium mixture according to claim 1, characterized in that, The high-efficiency cation exchange packing material is a silica gel surface polar group bonded phase packing material, and its ion exchange functional group is sulfonic acid group.

6. The method for separating and purifying indium from a cadmium-indium mixture according to claim 1, characterized in that, The mobile phase is a mixed solution of organic acid and water.

7. The method for separating and purifying indium from a cadmium-indium mixture according to claim 6, characterized in that, The organic acid is one of oxalic acid, citric acid, α-hydroxyisobutyric acid (HIBA), or 2-hydroxy-2-methylbutyric acid.

8. The method for separating and purifying indium from a cadmium-indium mixture according to claim 6, characterized in that, The concentration of organic acids in the mobile phase is 10~400 mM.

9. A method for separating and purifying indium from a cadmium-indium mixture according to claim 6, characterized in that, The mobile phase has a pH of 2.0 to 5.5 and a flow rate of 0.20 to 40 mL / min.

10. The method for separating and purifying indium from a cadmium-indium mixture according to claim 1, characterized in that, The elution conditions are isocratic elution or gradient elution, and the column temperature is 10~60℃.

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