Method for determining the content of relevant metal elements in yttrium-containing glass microspheres and its use

Abstract

The present application discloses a method for determining the content of relevant metal elements in yttrium-containing glass microspheres, the method comprising: mixing the yttrium-containing glass microspheres with a first acidic mixture for digestion to obtain a turbid solution; centrifuging the turbid solution to obtain a supernatant and an insoluble precipitate; mixing the insoluble precipitate with a second acidic mixture for digestion to obtain a clear solution; combining the clear solution and the supernatant for detection to obtain the content of the relevant metal elements; wherein the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid. The method can accurately and efficiently determine the content of relevant metal elements in yttrium-containing glass microspheres, and can solve the problem that yttrium-containing glass microspheres are difficult to digest, and greatly reduces the influence of the microsphere digestion process on the test results, thereby improving the accuracy of the method.

Description

[0001] This application is a divisional application of the Chinese patent application with application number 202310498613.1, application date May 5, 2023, and invention name “Method for determining the content of relevant metal elements in yttrium-containing glass microspheres and its use”. Technical Field

[0002] The present application relates to the field of detection technology, and in particular to a method for determining the content of relevant metal elements in yttrium-containing glass microspheres and its use. Background Art

[0003] Liver cancer is a highly malignant cancer. More than 60% of patients are diagnosed at an advanced stage and have lost the chance of surgical resection. 90 Y] Glass microsphere injection is a new non-surgical treatment method that uses glass microsphere embolization and local radiotherapy. Clinical applications have shown that it has broad prospects in the treatment of internal radiation liver segment / lobe resection, transitional / downgrade treatment before liver transplantation, liver cancer recurrence after liver resection, and palliative treatment of advanced liver cancer. 89 Y] glass microspheres are yttrium[ 90 Y] glass microspheres are made of a certain proportion of yttrium oxide, aluminum oxide and silicon oxide. The determination of the metal elements is a key item in its quality control. Therefore, it is important to establish an accurate and efficient method for determining the content of the metal elements. 90 Y] The quality control and administration safety of glass microsphere injection are crucial.

[0004] The current technologies for the determination of metal elements mainly include inductively coupled plasma optical emission spectroscopy (ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence spectroscopy (XRF). Among them, the ICP-MS method has good sensitivity, repeatability and accuracy. Summary of the invention

[0005] The premise for accurately determining the content of each component of yttrium-containing glass microspheres is that the glass microspheres can be effectively digested without introducing interference or adversely affecting the determination. For general glass, the main component is silicon dioxide, which has a simple composition. The current dissolution methods are mainly sodium-alkali melting method and acid dissolution method, which are simple to operate, efficient and fast. The sodium-alkali melting method uses sodium hydroxide and sodium carbonate as flux, which are dissolved in an acidic aqueous solution after high-temperature melting to prepare a clear solution. However, experimental results show that yttrium-containing glass microspheres cannot be digested by this method, and the high concentration of alkali metals introduced by this method will also affect the detection results of ICP-OES. When using the acid dissolution method, hydrofluoric acid is necessary, but the silicon fluoride generated by the reaction of silicon dioxide and hydrofluoric acid is a gas. Because the volatilization of the gas will cause inaccurate determination of the silicon dioxide content, this method is also not available.

[0006] In order to solve the above technical problems, the present application provides a method for determining the content of relevant metal elements in yttrium-containing glass microspheres. The method can accurately determine the content of relevant metal elements in yttrium-containing glass microspheres, and the method is simple and efficient to operate.

[0007] The specific technical solutions of this application are as follows:

[0008] 1. A method for determining the content of relevant metal elements in yttrium-containing glass microspheres, comprising:

[0009] Mixing the yttrium-containing glass microspheres with the first acidic mixture to digest and obtain a turbid solution;

[0010] Centrifuging the turbid liquid to obtain a supernatant and an insoluble precipitate;

[0011] mixing the insoluble precipitate with a second acidic mixture to digest the precipitate to obtain a clear solution;

[0012] The clear solution and the supernatant are combined for detection to obtain the content of the relevant metal elements;

[0013] Wherein, the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid.

[0014] 2. The method according to item 1, wherein the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid.

[0015] 3. The method according to item 2, wherein the volume ratio of concentrated nitric acid to concentrated hydrochloric acid in the first acidic mixture is 6:(0.2-1.2), preferably 6:(0.4-1).

[0016] 4. The method according to item 2 or 3, wherein the volume ratio of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 6:(0.5-2), preferably 6:(0.8-1.5).

[0017] 5. A method according to any one of items 1-4, wherein the mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(6-12) (mg / mL).

[0018] 6. A method according to any one of items 1-5, wherein the mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(4-10) (mg / mL).

[0019] 7. The method according to any one of items 1 to 6, wherein the maximum temperature during digestion is 200-250°C, preferably 210-230°C;

[0020] Preferably, the maximum temperature is maintained for 60-120 min during digestion.

[0021] 8. The method according to any one of items 1 to 7, wherein the detection is performed by inductively coupled plasma-mass spectrometry, inductively coupled plasma-atomic emission spectrometry or inductively coupled plasma-atomic absorption spectrometry.

[0022] 9. The method according to any one of items 1 to 8, wherein the relevant metal element is selected from one or more of cadmium, mercury, lead, arsenic, cobalt, nickel, vanadium, lithium, antimony and copper.

[0023] 10. Use of a first acidic mixture and a second acidic mixture for digesting yttrium-containing glass microspheres.

[0024] 11. The use according to item 10, wherein the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid.

[0025] 12. The use according to item 11, wherein the mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(6-12) (mg / mL).

[0026] 13. The use according to item 11 or 12, wherein the mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(4-10) (mg / mL).

[0027] 14. The use according to any one of items 11 to 13, wherein the first acid mixture and / or the second acid mixture is the first acid mixture and / or the second acid mixture involved in any one of items 3 to 4.

[0028] Effects of the Invention

[0029] The method described in this application can accurately and efficiently determine the content of relevant metal elements in yttrium-containing glass microspheres. The provided method can solve the problem that yttrium-containing glass microspheres are difficult to digest, and greatly reduce the impact of the microsphere digestion process on the test results, thereby improving the accuracy of the method. In addition, the limits of relevant element impurities are very low (refer to ICH Q3D). This application can accurately determine extremely low levels of relevant metal elements, which is of great significance for clinical drug safety. DETAILED DESCRIPTION

[0030] The embodiments described below are described in detail for the present application. Although specific embodiments of the present application are shown, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art.

[0031] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the functional differences of components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" are open-ended terms and should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present application, but the description is based on the general principles of the specification and is not intended to limit the scope of the present application. The scope of protection of the present application shall be determined by the attached claims.

[0032] The present application provides a method for determining the content of relevant metal elements in yttrium-containing glass microspheres, comprising:

[0033] Mixing the yttrium-containing glass microspheres with the first acidic mixture to digest and obtain a turbid solution;

[0034] Centrifuging the turbid liquid to obtain a supernatant and an insoluble precipitate;

[0035] mixing the insoluble precipitate with a second acidic mixture to digest the precipitate to obtain a clear solution;

[0036] The clear solution and the supernatant are combined and tested to obtain the content of the relevant metal elements. In some embodiments, the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid.

[0037] In the present application, the relevant metal elements refer to drug-related substances introduced during the production process of yttrium-containing glass microspheres or generated during the preparation process, which may have an adverse effect on the safety, effectiveness, quality, etc. of the drug. For example, the relevant metal elements may be cadmium, mercury, lead, arsenic, cobalt, nickel, vanadium, lithium, antimony, copper, etc.

[0038] In the present application, the digestion refers to dissolving the yttrium-containing glass microspheres using a solvent to obtain a dissolved solution. In the present application, the solvent refers to the first acid mixture and the second acid mixture.

[0039] In the present application, the yttrium-containing glass microspheres refer to glass microspheres containing yttrium elements, for example, yttrium [89 Y] glass microspheres or yttrium[ 90 Y] Glass microspheres.

[0040] The yttrium-containing glass microspheres have special properties and cannot be digested by conventional methods. The method described in the present application can digest the yttrium-containing glass microspheres and accurately determine the content of relevant metal elements in the glass microspheres.

[0041] For yttrium-containing glass microspheres, they contain yttrium oxide, aluminum oxide and silicon dioxide, wherein, by mass percentage in the yttrium-containing glass microspheres, the content of yttrium oxide is 10%-75%, the content of aluminum oxide is 10%-60%, and the content of silicon dioxide is 10-70%. For example, for yttrium-containing glass microspheres, the content of yttrium oxide can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, etc.;

[0042] The content of aluminum oxide can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, etc.;

[0043] The silicon dioxide content can be 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70%, etc.

[0044] In this application, the concentrated nitric acid refers to commercially available concentrated nitric acid with a mass fraction of about 68%;

[0045] The concentrated hydrochloric acid refers to commercially available concentrated hydrochloric acid with a mass fraction of about 37%;

[0046] The hydrofluoric acid is a commercially available hydrofluoric acid having a mass fraction of about 40%.

[0047] The present application uses a first acid mixture and a second acid mixture to digest the yttrium-containing glass microspheres, thereby being able to accurately determine the content of relevant metal elements in the yttrium-containing glass microspheres.

[0048] In some embodiments, the volume ratio of concentrated nitric acid to concentrated hydrochloric acid in the first acidic mixture is 6:(0.2-1.2), preferably 6:(0.4-1).

[0049] For example, the volume ratio (V) of concentrated nitric acid to concentrated hydrochloric acid in the first acidic mixture is 浓硝酸 :V 浓盐酸 ) can be 6:0.2, 6:0.3, 6:0.4, 6:0.5, 6:0.6, 6:0.7, 6:0.8, 6:0.9, 6:1, 6:1.1, 6:1.2, etc.

[0050] In some embodiments, the volume ratio of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 6:(0.5-2), preferably 6:(0.8-1.5).

[0051] For example, the volume ratio (V) of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 浓硝酸 :V 氢氟酸 ) can be 6:0.5, 6:0.6, 6:0.7, 6:0.8, 6:0.9, 6:1.0, 6:1.1, 6:1.2, 6:1.3, 6:1.4, 6:1.5, 6:1.6, 6:1.7, 6:1.8, 6:1.9, 6:2.0, etc.

[0052] In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(6-12) (mg / mL).

[0053] For example, the mass volume ratio (m 含钇玻璃微球 :v 第一酸性混合物 ) can be 50:6 (mg / mL), 50:7 (mg / mL), 50:8 (mg / mL), 50:9 (mg / mL), 50:10 (mg / mL), 50:11 (mg / mL), 50:12 (mg / mL), etc.

[0054] In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(4-10) (mg / mL).

[0055] For example, the mass volume ratio (m 含钇玻璃微球 :v 第二酸性混合物 ) can be 50:4 (mg / mL), 50:5 (mg / mL), 50:6 (mg / mL), 50:7 (mg / mL), 50:8 (mg / mL), 50:9 (mg / mL), 50:10 (mg / mL), etc.

[0056] In some embodiments, the maximum temperature during digestion is 200-250°C, preferably 210-230°C;

[0057] Preferably, the maximum temperature is maintained for 60-120 min during digestion.

[0058] For example, the maximum temperature during digestion can be 200°C, 210°C, 220°C, 230°C, 240°C, 250°C;

[0059] The maximum temperature maintenance time during digestion can be 60min, 70min, 80min, 90min, 100min, 110min, 120min, etc.

[0060] In some embodiments, the detection is performed by inductively coupled plasma-mass spectrometry, inductively coupled plasma-atomic emission spectrometry, or inductively coupled plasma-atomic absorption spectrometry.

[0061] In the present application, inductively coupled plasma-mass spectrometry, inductively coupled plasma-atomic emission spectrometry and inductively coupled plasma-atomic absorption spectrometry are all conventional methods in the art. The present application does not impose any restrictions on the parameters in inductively coupled plasma-mass spectrometry, inductively coupled plasma-atomic emission spectrometry and inductively coupled plasma-atomic absorption spectrometry, and they are measured using conventional parameters in the art.

[0062] In some embodiments, the method for determining the content of the relevant metal element in the yttrium-containing glass microspheres comprises: mixing the yttrium-containing glass microspheres with a first acidic mixture to digest and obtain a turbid solution; centrifuging the turbid solution to obtain a supernatant and an insoluble precipitate; mixing the insoluble precipitate with a second acidic mixture to digest and obtain a clear solution; combining the clear solution and the supernatant to detect and obtain the content of the relevant metal element. In some embodiments, the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid. In some embodiments, the volume ratio of concentrated nitric acid to concentrated hydrochloric acid in the first acidic mixture is 6:(0.2-1.2), preferably 6:(0.4-1). In some embodiments, the volume ratio of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 6:(0.5-2), preferably 6:(0.8-1.5). In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(6-12) (mg / mL). In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(4-10) (mg / mL). In some embodiments, the maximum temperature during digestion is 200-250°C, preferably 210-230°C; preferably, the maximum temperature is maintained for 60-120 min during digestion. In some embodiments, the detection is performed using inductively coupled plasma-mass spectrometry. In some embodiments, the relevant metal elements are selected from one or more of cadmium, mercury, lead, arsenic, cobalt, nickel, vanadium, lithium, antimony and copper.

[0063] The present application adopts the above-mentioned method to digest the yttrium-containing glass microspheres, which can solve the problem that the yttrium-containing glass microspheres are difficult to digest, and the method has no interference with the test. In addition, the method described in the present application can accurately determine the content of relevant metal elements in the glass microspheres, and the method has good stability and high accuracy.

[0064] The present application provides the use of a first acidic mixture and a second acidic mixture for digesting yttrium-containing glass microspheres. In some embodiments, the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid.

[0065] In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(6-12) (mg / mL).

[0066] For example, the mass volume ratio (m 含钇玻璃微球 :v 第一酸性混合物 ) can be 50:6 (mg / mL), 50:7 (mg / mL), 50:8 (mg / mL), 50:9 (mg / mL), 50:10 (mg / mL), 50:11 (mg / mL), 50:12 (mg / mL), etc.

[0067] In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(4-10) (mg / mL).

[0068] For example, the mass volume ratio (m 含钇玻璃微球 :v 第二酸性混合物 ) can be 50:4 (mg / mL), 50:5 (mg / mL), 50:6 (mg / mL), 50:7 (mg / mL), 50:8 (mg / mL), 50:9 (mg / mL), 50:10 (mg / mL), etc.

[0069] In some embodiments, the first acidic mixture and / or the second acidic mixture is the first acidic mixture and / or the second acidic mixture mentioned above.

[0070] In some embodiments, the first acidic mixture and the second acidic mixture are used for digesting yttrium-containing glass microspheres, wherein the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid. In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(6-12) (mg / mL). In some embodiments, the mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(4-10) (mg / mL). In some embodiments, the first acidic mixture and / or the second acidic mixture are the first acidic mixture and / or the second acidic mixture involved above.

[0071] The present application uses the first acid mixture and the second acid mixture to digest the glass microspheres, which can completely digest the glass microspheres, thereby accurately determining the content of the relevant metal elements in the glass microspheres.

[0072] Example

[0073] The present application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % means wt%, i.e., weight percentage. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be obtained commercially.

[0074] Example 1

[0075] Take yttrium 89 Y] 6 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in a reaction tank, 8 mL of the first acidic mixture (the volume ratio of concentrated nitric acid to concentrated hydrochloric acid was 6:0.2, 6:0.4, 6:0.6, 6:0.8, 6:1, 6:1.2, respectively) were added, and the sample was digested using a microwave digestion instrument (Anton Paar, MW5000). After the digestion was completed, the solution in the digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volumetric bottle, 5 mL of diluent (2% nitric acid aqueous solution) was transferred to the centrifuge tube, shaken to fully mix with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volumetric bottle. The bottom precipitate was completely transferred back to the digestion tank several times using 5 mL of the second acidic mixture (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:2), and the bottom precipitate was digested using a microwave digestion instrument. After digestion, transfer the solution in the above digestion tank to the same volumetric flask, wash the inner wall of the digestion tank several times with a diluent, and transfer the washing solution to the volumetric flask, add 2mL nitric acid, dilute with a diluent, and mix. Transfer 5mL of the above solution to a 10mL plastic volumetric flask, dilute with a diluent, mix, and observe whether the solution is clear. The results are shown in Table 2.

[0076] The microwave digestion program is shown in Table 1.

[0077] Table 1 Microwave digestion instrument program

[0078] Target temperature (℃) Climbing time (min) Insulation time (min) 220 10 60

[0079] The final digestion status is shown in Table 2.

[0080] Table 2 Microsphere digestion results in Example 1

[0081] Volume ratio of concentrated nitric acid solution to concentrated hydrochloric acid Digestion results 6：0.2 Basic dissolution 6︰0.4 Completely dissolved 6:0.6 Completely dissolved 6︰0.8 Completely dissolved 6︰1 Completely dissolved 6︰1.2 Basic dissolution

[0082] The results show that the volume ratio of concentrated nitric acid to concentrated hydrochloric acid in the first acid mixture is 6:0.2-1.2, which can basically digest the microspheres. However, considering the stability of subsequent tests, the preferred volume ratio of concentrated nitric acid to concentrated hydrochloric acid is 6:0.4-1.

[0083] Example 2

[0084] Take yttrium 89 Y] 5 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in a reaction tank, 8 mL of the first acidic mixture (the volume ratio of concentrated nitric acid to concentrated hydrochloric acid was 6:1) was added, and the sample was digested using a microwave digestion instrument. After the digestion was completed, the solution in the above digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volume bottle, 5 mL of diluent was transferred to the centrifuge tube, shaken to fully mix with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volume bottle. The bottom precipitate was completely transferred back to the digestion tank using 5 mL of the second acidic mixture several times (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:0.5, 6:0.8, 6:1, 6:1.5, 6:2, respectively), and the bottom precipitate was digested using a microwave digestion instrument. After digestion, transfer the solution in the above digestion tank to the same volumetric flask, wash the inner wall of the digestion tank several times with a diluent, and transfer the washing solution to the volumetric flask, add 2 mL of nitric acid, dilute with a diluent, and mix. Transfer 5 mL of the above solution to a 10 mL plastic volumetric flask, dilute with a diluent, mix, and observe whether the solution is clear. The results are shown in Table 3.

[0085] The microwave digestion procedure was the same as in Example 1.

[0086] The results of microsphere digestion are shown in Table 3.

[0087] Table 3 Microsphere digestion results in Example 2

[0088] Volume ratio of concentrated nitric acid to hydrofluoric acid Digestion results 6：0.5 Basic dissolution 6︰0.8 Completely dissolved 6︰1 Completely dissolved 6︰1.5 Completely dissolved 6︰2 Completely dissolved

[0089] The results show that the volume ratio of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 6:0.5-2, which can basically digest the microspheres. However, considering the stability of subsequent tests and the tolerance of the ICPMS equipment, the preferred volume ratio of concentrated nitric acid to hydrofluoric acid is 6:0.8-1.5.

[0090] Example 3

[0091] Take yttrium 89 Y] 4 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in reaction tanks, 6 mL, 8 mL, 10 mL, and 12 mL of the first acidic mixture (the volume ratio of concentrated nitric acid to concentrated hydrochloric acid was 6:1) were added, and the samples were digested using a microwave digestion instrument. After the digestion was completed, the solution in the above digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volume bottle, 5 mL of diluent was transferred to the centrifuge tube, shaken to fully mix with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volume bottle. The bottom precipitate was completely transferred back to the digestion tank (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:1) using 5 mL of the second acidic mixture in multiple times, and the bottom precipitate was digested using a microwave digestion instrument. After digestion, transfer the solution in the above digestion tank to the same volumetric flask, wash the inner wall of the digestion tank several times with a diluent, and transfer the washing solution to the volumetric flask, add 2 mL of nitric acid, dilute with a diluent, and mix. Transfer 5 mL of the above solution to a 10 mL plastic volumetric flask, dilute with a diluent, mix, and observe whether the solution is clear. The results are shown in Table 4.

[0092] The microwave digestion procedure was the same as in Example 1.

[0093] The microsphere digestion results are shown in Table 4.

[0094] Table 4 Microsphere digestion results of Example 3

[0095] Ratio of microspheres to first acidic mixture (mass: volume) Digestion results 50：6 Basic dissolution 50︰8 Completely dissolved 50︰10 Completely dissolved 50︰12 Completely dissolved

[0096] The results show that the microspheres can be digested when the mass volume ratio of the microspheres to the first acid mixture is 50:6-12. Considering the tolerance of subsequent equipment, the ratio of the first acid mixture cannot be too high, so it is not recommended that the mass volume ratio of the microspheres to the first acid mixture exceed 50:12.

[0097] Example 4

[0098] Take yttrium 89Y] 5 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in a reaction tank, 8 mL of the first acidic mixture (the volume ratio of concentrated nitric acid to concentrated hydrochloric acid was 6:1) was added, and the sample was digested using a microwave digestion instrument. After the digestion was completed, the solution in the above digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volume bottle, 5 mL of diluent was transferred to the centrifuge tube, shaken to fully mix with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volume bottle. The bottom precipitate was completely transferred back to the digestion tank (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:1) using 4 mL, 5 mL, 6 mL, 8 mL, and 10 mL of the second acidic mixture in multiple times, and the bottom precipitate was digested using a microwave digestion instrument. After digestion, transfer the solution in the above digestion tank to the same volumetric flask, wash the inner wall of the digestion tank several times with a diluent, and transfer the washing solution to the volumetric flask, add 2 mL of nitric acid, dilute with a diluent, and mix. Transfer 5 mL of the above solution to a 10 mL plastic volumetric flask, dilute with a diluent, mix, and observe whether the solution is clear. The results are shown in Table 5.

[0099] The microwave digestion procedure was the same as in Example 1.

[0100] The results are shown in Table 5.

[0101] Table 5 Microsphere digestion results in Example 4

[0102] Ratio of microspheres to second acid mixture (mass:volume) Digestion results 50：4 Basic dissolution 50︰5 Completely dissolved 50︰6 Completely dissolved 50︰8 Completely dissolved 50:10 Completely dissolved

[0103] The results show that the microspheres can be digested when the mass volume ratio of the microspheres to the second acid mixture is 50:4-10. Considering the tolerance of subsequent equipment, the ratio of the second acid mixture cannot be too high, so it is not recommended to exceed 50:10.

[0104] Example 5

[0105] Take yttrium 89Y] 6 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in a reaction tank, 8 mL of the first acidic mixture (the volume ratio of concentrated nitric acid to concentrated hydrochloric acid was 6:1) was added, and the samples were digested using the following 6 microwave digestion procedures. After the digestion was completed, the solution in the above digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volume bottle, 5 mL of diluent was transferred to the centrifuge tube, shaken to fully mix with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volume bottle. The bottom precipitate was completely transferred back to the digestion tank using 5 mL of the second acidic mixture several times (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:1), and the bottom precipitate was digested using the same microwave digestion procedure as above. After the digestion was completed, the solution in the above digestion tank was transferred to the same volume bottle, the inner wall of the digestion tank was washed several times with the diluent, and the washing solution was transferred to the volume bottle together, 2 mL of nitric acid was added, and the volume was fixed with the diluent, and mixed. Pipette 5 mL of the above solution into a 10 mL plastic volumetric flask, dilute to volume, mix, and observe whether the solution is clear. The results are shown in Table 8.

[0106] The microwave digestion procedures are shown in Table 7.

[0107] Table 7 Microwave digestion instrument program

[0108] Target temperature(℃) Climbing time (min) Holding time (min) 1 200 10 60 2 210 10 60 3 220 10 60 4 230 10 60 5 240 10 60 6 250 10 60

[0109] The results are shown in Table 8.

[0110] Table 8 Microsphere digestion results in Example 5

[0111]

[0112]

[0113] As can be seen from Table 8, the higher the digestion temperature, the more conducive it is to the digestion of the microspheres. Considering the tolerance of the microwave digestion instrument, the temperature should not be too high, preferably 210°C-230°C. Similarly, the longer the digestion time, the more conducive it is to the digestion of the microspheres.

[0114] Example 6 Repeatability Study

[0115] Take yttrium 89Y] 6 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in reaction tanks, and standard solutions of each element (equivalent to 100% level of the limit standard of each element) were added, and 8 mL of the first acid mixture (the volume ratio of concentrated nitric acid to concentrated hydrochloric acid was 6:1) was added, and the sample was digested using a microwave digestion instrument. After the digestion was completed, the solution in the above digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volume bottle, 5 mL of diluent was transferred to the centrifuge tube, shaken to fully mix with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volume bottle. The bottom precipitate was completely transferred back to the digestion tank several times using 5 mL of the second acid mixture (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:1), and the bottom precipitate was digested using a microwave digestion instrument. After digestion, transfer the solution in the above digestion tank to the same volumetric flask, wash the inner wall of the digestion tank several times with a diluent, and transfer the washing solution to the volumetric flask, add 2 mL of nitric acid, dilute with a diluent, and mix. Transfer 5 mL of the above solution to a 10 mL plastic volumetric flask, dilute with a diluent, mix, and use ICP-MS to determine the content of the relevant metal elements in the glass microspheres. The parameters are shown in Table 9, and the RSD is shown in Table 10.

[0116] Note: All reagents used above are of trace metal grade.

[0117] The microwave digestion procedure was the same as in Example 1.

[0118] Table 9

[0119]

[0120]

[0121] Table 10 Repeatability results of each element in Example 6

[0122] Elements to be measured RSD% Cd 3.4 Hg 1.3 Pb 4.0 As 10 Co 6.9 Ni 3.9 V 2.2 Li 0.9 Sb 1.8 Cu 1.7

[0123] The results showed that the RSD% of each element in the six samples was less than 20%, and the repeatability of the method was good.

[0124] Example 7 Accuracy Study

[0125] Take yttrium 89Y] 9 portions of glass microspheres (about 50 mg each, accurately weighed) were placed in reaction tanks, and standard solutions of each element (equivalent to 30%, 100%, and 150% of the limit level of each element) were added. 8 mL of the first acid mixture (the volume ratio of nitric acid to hydrochloric acid was 6:1) was added, and the sample was digested using a microwave digestion instrument. After the digestion was completed, the solution in the above digestion tank was transferred to a centrifuge tube, centrifuged at 1000 rpm for 5 minutes, the supernatant was taken to a 100 mL plastic volume bottle, 5 mL of diluent was transferred to the centrifuge tube, shaken to mix thoroughly with the bottom precipitate, centrifuged under the same conditions, and the supernatant was transferred to the same volume bottle. The bottom precipitate was completely transferred back to the digestion tank several times using 5 mL of the second acid mixture (the volume ratio of concentrated nitric acid to hydrofluoric acid was 6:1), and the bottom precipitate was digested using a microwave digestion instrument. After digestion, the solution in the digestion tank was transferred to the same volumetric flask, the inner wall of the digestion tank was washed several times with a diluent, and the washing solution was transferred to the volumetric flask, 2 mL of nitric acid was added, the volume was fixed with a diluent, and the mixture was mixed. 5 mL of the above solution was transferred to a 10 mL plastic volumetric flask, the volume was fixed with a diluent, and the mixture was mixed. The content of the relevant metal elements in the glass microspheres was determined by the same method as in Example 6, and the recovery results are shown in Table 11.

[0126] The microwave digestion procedure was the same as in Example 1.

[0127] Table 11 Element recovery results in Example 7

[0128]

[0129] As can be seen from Table 11, the recovery results of each element in the microspheres are between 70% and 150%, indicating that the accuracy of the method is good.

[0130] Comparative Example 1

[0131] Take yttrium 89 Y] About 25 mg of glass microspheres were accurately weighed and placed in a platinum crucible. About 200 mg of flux (the ratio of glass microspheres to flux was 1:8, and the mass ratio of anhydrous sodium carbonate and boric acid in the flux was 2:1) were added in sequence. Mixed well, placed in a muffle furnace, melted at 800°C for 60 minutes, and after natural cooling, 15 mL of 1 M nitric acid solution was added. Heat and stir to make a complete solution, and transfer to a 100 mL volumetric flask. The crucible was cleaned with 1 M nitric acid solution in small amounts and multiple times. The washings were combined in the volumetric flask and diluted to volume with 1 M nitric acid solution.

[0132] Note: The reagents used above are all of metal-free grade.

[0133] When ICP-MS was used to detect the element content, it was found that the flux matrix introduced when melting the microspheres was too high, which had a great impact on the detector. There were major problems with the stability of the test system and it could not be used.

[0134] Comparative Example 2

[0135] Comparative Example 2 Compared with Example 1, the first acid mixture and the second acid mixture were replaced by different acids such as perchloric acid, sulfuric acid, phosphoric acid, nitric acid, hydrochloric acid, or mixed acids with different component ratios, but no clear solution could be obtained, that is, the microspheres could not be completely digested. Therefore, it cannot be guaranteed that all elemental impurities are dissolved, that is, the content of elemental impurities is lower than the actual value, and the accuracy of the method cannot be guaranteed.

[0136] The above is only the preferred embodiment of the present application, and does not limit the present application in other forms. Any technician familiar with the profession may use the above disclosed technical content to change or modify it into an equivalent embodiment with equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiment based on the technical essence of the present application without departing from the technical solution of the present application still falls within the protection scope of the technical solution of the present application.

Claims

1. A method for determining the content of relevant metal elements in yttrium-containing glass microspheres, comprising: Mixing the yttrium-containing glass microspheres with the first acidic mixture to digest and obtain a turbid solution; Centrifuging the turbid liquid to obtain a supernatant and an insoluble precipitate; mixing the insoluble precipitate with a second acidic mixture to digest the precipitate to obtain a clear solution; The clear solution and the supernatant are combined for detection to obtain the content of the relevant metal elements; Wherein, the first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid; The volume ratio of concentrated nitric acid to concentrated hydrochloric acid in the first acidic mixture is 6:(0.6-1); The volume ratio of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 6:(1-1.5); The mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(8-12) (mg / mL); The mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(5-10) (mg / mL); The relevant metal elements are selected from one or more of cadmium, mercury, lead, arsenic, cobalt, nickel, vanadium, lithium, antimony and copper.

2. The method according to claim 1, wherein the maximum temperature during digestion is 210-230°C.

3. The method according to claim 1, wherein: The maximum temperature is maintained for 60-120 minutes during digestion.

4. The method according to claim 1, wherein: The detection is carried out by inductively coupled plasma-mass spectrometry, inductively coupled plasma-atomic emission spectrometry or inductively coupled plasma-atomic absorption spectrometry.

5. Use of the first acidic mixture and the second acidic mixture in digesting yttrium-containing glass microspheres; The first acidic mixture is a mixture of concentrated nitric acid and concentrated hydrochloric acid, and the second acidic mixture is a mixture of concentrated nitric acid and hydrofluoric acid; The mass volume ratio of the yttrium-containing glass microspheres to the first acidic mixture is 50:(8-12) (mg / mL); The mass volume ratio of the yttrium-containing glass microspheres to the second acidic mixture is 50:(5-10) (mg / mL); The volume ratio of concentrated nitric acid to concentrated hydrochloric acid in the first acidic mixture is 6:(0.6-1); The volume ratio of concentrated nitric acid to hydrofluoric acid in the second acidic mixture is 6:(1-1.5); The method for digesting yttrium-containing glass microspheres is as follows: Mixing the yttrium-containing glass microspheres with the first acidic mixture to digest and obtain a turbid solution; Centrifuging the turbid liquid to obtain a supernatant and an insoluble precipitate; The insoluble precipitate is mixed with a second acidic mixture for digestion to obtain a clear solution.

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