Preparation and application of bonded silica gel high performance liquid chromatography filler with composite structure

Abstract

The invention discloses preparation and application of a composite structure bonded silica gel high performance liquid chromatography filler, and relates to the technical field of high performance liquid chromatography filler preparation, and the preparation method comprises the following steps: (1) selecting a silicon source, generally taking tetraethoxysilane as a basic silicon source, and preparing by adopting a drying method, a polymerization reaction method, a two-time gel method and the like, (2) modifying silica gel, and (3) preparing the composite structure bonded silica gel high performance liquid chromatography filler. Surface chemical modification and overall modification are combined, a traditional common surface modification method is changed, (3) electrostatic shielding is adopted, silica gel can be positively charged, positively charged solutes can be repelled, and solute molecules are protected against ion exchange with dissociated silicon hydroxyl; according to the present invention, the three methods are combined to prepare the filler, such that the prepared filler has more selectivity, and the preparation of the composite structure bonded silica gel high performance liquid chromatography filler can be achieved according to different conditions.

Description

Technical Field

[0001] The invention relates to the technical field of high performance liquid chromatography filler preparation, and more specifically to the preparation and application of a composite structure bonded silica gel high performance liquid chromatography filler. Background Art

[0002] There are many types of silica gel bonding. In addition to separating ordinary organic compounds, the separation range of composite structure bonded silica gel is different according to its different characteristics. In terms of application, it is mainly concentrated in the analysis of biological and pharmaceutical samples. Silica gel HPLC fillers play an important role in the separation and analysis of small molecules and polymers. The chromatographic stationary phase is the core part of the HPLC system. In order to meet the requirements of high selectivity and high sensitivity when analyzing complex samples, the development of new chromatographic stationary phases with high separation efficiency and good selectivity has become a hot topic in the field of separation science.

[0003] The Chinese patent with patent application publication number CN115569639A discloses a modified silica sphere novel stationary phase high performance liquid chromatography filler and its preparation method and application. By bonding a spherical covalent organic framework material on the surface of the silica sphere and covering the outer layer with thio-β-cyclodextrin, a high performance liquid chromatography filler including silica spheres, spherical covalent organic framework materials bonded to the surface of the silica spheres, and thio-β-cyclodextrin covered on the outer layer of the spherical covalent organic framework material is obtained. The filler of the present invention has the excellent physical structure of silica gel filler such as high mechanical strength, good physical and chemical properties, can be used in reverse phase separation mode, and has good chiral separation ability, and has the advantages of fast separation speed and high separation selectivity. At the same time, the preparation method of the high performance liquid chromatography filler of the present invention is simple and easy to operate.

[0004] However, the current HPLC fillers have many defects in the preparation process due to the single preparation method. The overall structure and performance of the prepared HPLC fillers are poor, the application range is relatively single, the orientation is poor, and it is impossible to achieve the desired effect according to different structures.

[0005] And performance indicators are used in corresponding fields respectively, and the performance of the prepared high performance liquid chromatography filler products is imperfect. Summary of the invention

[0006] In order to overcome the above-mentioned defects of the prior art, the embodiments of the present invention provide a preparation and application of a composite structure bonded silica gel high performance liquid chromatography filler, so as to solve the problem that the current high performance liquid chromatography filler mentioned in the above background technology has large defects in the preparation process due to the single preparation method, the overall structural performance of the prepared high performance liquid chromatography filler is poor, the application range is relatively single, the orientation is poor, and it is impossible to apply to the corresponding field range according to different structures and performance indicators, and the performance of the prepared high performance liquid chromatography filler product is imperfect.

[0007] To achieve the above object, the present invention adopts the following technical solution:

[0008] The present invention provides a method for preparing a composite structure bonded silica gel high performance liquid chromatography filler, characterized in that the preparation method comprises the following steps:

[0009] 1. Select the silicon source, generally based on ethyl orthosilicate, and prepare it by drying method, polymerization reaction method and double gel method;

[0010] 2. Silicone modification, using a combination of surface chemical modification and overall modification, changes the traditional commonly used surface modification method, allowing the structure to better bond with the silica surface, and the stability is also better. At the same time, the auxiliary polymerization coating method effectively covers the residual silanol on the surface of the silica in the form of a cross-linking method;

[0011] 3. Electrostatic shielding can make silica gel carry positive charge, which will repel positively charged solutes and protect solute molecules from ion exchange with dissociated silanol groups, so that the coagulant solvent in the silica gel can be effectively distributed, improve selectivity, and further shield the silanol groups, so that the corresponding molecules

[0012] The compounds can react with the silica gel surface in a directional manner, which is beneficial for the composite structure bonded silica gel to be used for biological separation and analysis.

[0013] Preferably, in step 1, the specific method of the drying method is: firstly, silicate is polymerized to form a sol, and the sol is a liquid, which is conducive to spray drying. According to the spray principle, the silica sol is sprayed and dispersed, and then turned into a gel by vacuum drying.

[0014] Preferably, the specific method of the polymerization reaction method in step 1 is: silica sol in a gel state is encapsulated by a polymerization reaction in a silica sol dispersion system, and organic matter is removed by sintering to obtain porous silica microspheres.

[0015] Preferably, the specific method of the two-gel method in step 1 is: using two catalysis-gels, using the hydrolysis and polycondensation principle of the silicon source, to fix and nucleate the silica gel microspheres made of the silicon source body. This process is used to control the particle size of the silica gel filler and is carried out under acidic conditions. Template substances can be added during the process to regulate the silica gel pore structure;

[0016] The second catalysis is to age the silica gel filler under alkaline conditions to fix the silica gel filler. The two-step hydrolysis and polycondensation can effectively support silica gel HPLC fillers with the same average particle size.

[0017] Preferably, the specific method of surface chemical modification in step 2 is: bonding the organic compound to the silica gel surface through a chemical reaction, and reacting with the free silanol groups on the silica gel surface, and in the overall modification, on the basis of surface chemical modification, adding alkoxysilane to improve stability, so that the organic compound is evenly distributed on the surface of the silica gel filler.

[0018] Preferably, the specific method of the auxiliary polymerization coating method in step 2 is: during the modification process, inorganic materials are added to make the shape of the filler more regular, and to improve the mechanical strength, improve the shielding property of the surface of the silica gel filler, and reduce the dissolution of the silica gel filler during use.

[0019] Preferably, it is characterized in that the specific method of electrostatic shielding in step 2 is: using the principle of electrostatic shielding, the amine molecules in the silica gel filler can be positively charged, thereby repelling positively charged solutes, which is complementary to the above-mentioned polymerization coating method to further shield the excess silanol groups on the surface of the silica gel filler.

[0020] Preferably, the application of the composite structure bonded silica gel high performance liquid chromatography filler is characterized in that, as the application of the composite structure bonded silica gel high performance liquid chromatography filler in industrial, chemical and biological separation analysis, first the composite structure bonded silica gel high performance liquid chromatography filler products are selected and the preferred products are tested, and finally they are applied to different fields.

[0021] Preferably, the specific steps for selecting the composite structure bonded silica gel high performance liquid chromatography filler product are as follows: S1: select products according to their morphology, which are divided into amorphous silica gel fillers and spherical silica gel fillers, both of which can be used in industry, with spherical silica gel fillers being preferred, and amorphous silica gel fillers being alternatives based on cost budget; S2: according to the pore structure, they are divided into intervening pores, large pores, and super large pores, and the application range is selected according to the numerical range of the pore structure; S3: within the range of intervening pores, select industrial preparation, secondly, within the range of large pores, select separation and pharmaceutical manufacturing, and thirdly, within the range of super large pores, select separation of polymers and biomacromolecules; S4: perform quality testing on the selected high-quality products.

[0022] Preferably, the specific steps of the quality test described in S4 are divided into three stages, such as the first stage: pressure test, the micropores in the silica gel skeleton will affect the mechanical strength of the silica gel, resulting in the disadvantage of not being able to withstand pressure, therefore, a pressure test is required; the second stage: sample comparison, comparing the selected product with the qualified sample to ensure that the product has an effective surface area, so that the application field can be selected based on the surface area combined with the pore structure; the third stage: chemical stability test, determining the pH value range of the silica gel filler, and selecting a product with a wider pH value.

[0023] Silica gel filler with a wide range of values ​​can effectively solve the fluctuation of separation effect;

[0024] Preferably, the composite structure bonded silica gel high performance liquid chromatography filler is used in industry, pharmaceuticals and molecular fields.

[0025] Compared with the prior art, one or more of the above technical solutions have the following beneficial effects:

[0026] The present invention combines three methods for preparation, so that more selectivity can be prepared, and the preparation of composite structure bonded silica gel high performance liquid chromatography filler can be achieved according to different situations. The first drying method is prepared in combination with the spray principle, and chemical products such as catalysts are used for catalytic dispersion and curing, so that the particle size distribution range of the prepared composite structure bonded silica gel high performance liquid chromatography filler is relatively wide, and the application range and application rate in the market are relatively high. The second polymerization method uses polymerization reaction to encapsulate nano-scale silica gel into organic-inorganic silica gel balls with a composite structure. The preparation advantage of this method is that the prepared particle size is relatively uniform, but because the reaction conditions are uncontrollable, therefore, on this basis, the third preparation method, the double gel method, is combined, in which cross-linked sol is obtained by catalytic hydrolysis under acidic conditions, and then gelation is performed under alkaline conditions, and the gelled sol is aged. In this process, a template substance is added to regulate the silica gel pore structure on the silica gel surface, so as to ensure that the strength and pore structure of the prepared product are uniform, which is conducive to the preparation of small-particle composite structure bonded silica gel high performance liquid chromatography filler, and further expands the application range of the composite structure bonded silica gel high performance liquid chromatography filler;

[0027] The present invention adopts a variety of methods to modify the silicon source, combines surface modification with overall modification, improves the structural complexity of the silica gel filler and implements bonding, cooperates with the polymer coating method, improves the mechanical strength of the composite structure bonded silica gel high performance liquid chromatography filler, and can shield the excess silanol group on the silica gel surface, reducing the silica under alkaline conditions.

[0028] The gel is dissolved, and the polyoxyethylene is bonded to the outer surface of the composite structure bonded silica gel high performance liquid chromatography filler by polymerization method to form a hydrophilic layer, so as to achieve the separation of small molecule target substances, which can be applied to the separation and analysis of small molecule substances.

[0029] The present invention compares various indicators of composite structure bonded silica gel high performance liquid chromatography fillers and classifies them according to pore structure, compressive strength, chemical stability and pH value range, so as to be targeted for application in different fields with high accuracy and strong target orientation. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0031] In the attached picture:

[0032] Figure 1 It is a schematic diagram of the structure of the preparation process of the present invention;

[0033] Figure 2 It is a schematic diagram of the application process structure of the present invention;

[0034] Figure 3 This is a structural diagram of the test process of the preferred product of the present invention;

[0035] Figure 4 This is a schematic diagram of the product selection process structure of the present invention;

[0036] Figure 5 It is a schematic diagram of the test structure process structure of the present invention. DETAILED DESCRIPTION

[0037] In order to enable those skilled in the art to better understand the present invention, the following will provide a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, ordinary technicians in the field will not

[0038] All other embodiments obtained on the premise of creative work should fall within the scope of protection of this application.

[0039] It should be noted that the terms "first", "second", etc. in the specification and claims of the present application and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchanged where appropriate, so that the embodiments of the present application described here. In addition, the terms "including" and "having" and any of their variations are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0040] In this application, the terms "upper", "lower", "left", "right", "front", "back", "top", "bottom", "inside", "outside", "center", "vertical", "horizontal", "lateral", "longitudinal" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings. These terms are mainly used to better describe the present application and its embodiments, and are not used to limit the indicated devices, elements or components to have a specific orientation, or to be constructed and operated in a specific orientation.

[0041] In addition, some of the above terms may be used to express other meanings in addition to indicating orientation or positional relationship. For example, the term "on" may also be used to express a certain dependency or connection relationship in some cases. For those of ordinary skill in the art, the specific meanings of these terms in this application can be understood according to specific circumstances.

[0042] In addition, the terms "installed", "set", "provided with", "connected", "connected", and "socketed" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral structure; it can be a mechanical connection or an electrical connection; it can be directly connected or through an intermediate medium.

[0043] Indirect connection, or internal connection between two devices, elements or components. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0044] Embodiment 1:

[0045] See also Figures 1 to 5 , a method for preparing a composite structure bonded silica gel high performance liquid chromatography filler, the preparation method comprising the following steps:

[0046] 1. Select the silicon source, generally based on ethyl orthosilicate, and prepare it by drying method, polymerization reaction method and double gel method;

[0047] 2. Silicone modification, using a combination of surface chemical modification and overall modification, changes the traditional commonly used surface modification method, allowing the structure to better bond with the silica surface, and the stability is also better. At the same time, the auxiliary polymerization coating method effectively covers the residual silanol on the surface of the silica in the form of a cross-linking method;

[0048] 3. Electrostatic shielding can make silica gel carry a positive charge, which will repel positively charged solutes and protect the solute molecules from ion exchange with the dissociated silanol groups, so that the coagulant solvent in the silica gel can be effectively distributed, improve selectivity, and further shield the silanol groups, so that the corresponding molecules and compounds can react with the silica gel surface in a direction, which is conducive to the composite structure bonded silica gel for biological separation and analysis.

[0049] In step 1, the specific method of the drying method is: first, the silicate is polymerized to form a sol. The sol is a liquid, which is conducive to spray drying. According to the spray principle, the silica sol is sprayed into shape and dispersed, and then turned into a gel with vacuum drying.

[0050] The specific method of the polymerization reaction method in step 1 is: the silica sol in the gel state is subjected to a polymerization reaction in the silica sol dispersion system to encapsulate the silica sol, and the silica sol is removed by sintering.

[0051] After removing the organic matter, porous silica gel microspheres were obtained.

[0052] The specific method of the double gel method in step 1 is: using double catalysis-gel, using the hydrolysis and polycondensation principle of the silicon source, to fix the silica microspheres made of the silicon source body into nuclei. This process is used to control the particle size of the silica filler and is carried out under acidic conditions. Template substances can be added during the process to regulate the silica pore structure;

[0053] The second catalysis is to age the silica gel filler under alkaline conditions to fix the silica gel filler. The two-step hydrolysis and polycondensation can effectively support silica gel HPLC fillers with the same average particle size.

[0054] The specific method of surface chemical modification in step 2 is: bonding the organic compound to the silica surface through chemical reaction, and reacting with the free silanol groups on the silica surface. In the overall modification, on the basis of surface chemical modification, alkoxysilane is added to improve stability and allow the organic compound to be evenly distributed on the surface of the silica filler.

[0055] The specific method of the auxiliary polymerization coating method in step 2 is: in the process of modification, inorganic materials will be added to make the shape of the filler more regular, and to improve the mechanical strength, improve the shielding property of the surface of the silica gel filler, and reduce the dissolution of the silica gel filler during use.

[0056] The specific method of electrostatic shielding in step 2 is: using the principle of electrostatic shielding, the amine molecules in the silica gel filler can be positively charged, thereby repelling positively charged solutes, which is complementary to the above-mentioned polymerization coating method to further shield the excess silanol groups on the surface of the silica gel filler.

[0057] As the application of composite structure bonded silica HPLC filler in industrial, chemical and biological separation analysis, the composite structure bonded silica HPLC filler products are first selected and the preferred products are tested, and finally applied to different fields.

[0058] The specific steps for selecting composite structure bonded silica gel HPLC packing products are as follows: S1:

[0059] Products are selected according to their morphology, which are divided into amorphous silica fillers and spherical silica fillers. Both can be used in industry. Spherical silica fillers are preferred, and amorphous silica fillers can be selected based on cost budget. S2: According to the pore structure, they are divided into intervening pores, large pores, and super large pores. The application range is selected according to the numerical range of the pore structure. S3: Within the range of intervening pores, industrial preparation is selected, followed by separation and pharmaceutical manufacturing within the range of large pores, and then separation of polymers and biomacromolecules within the range of super large pores. S4: Quality testing is performed on the selected high-quality products.

[0060] The specific steps of the quality test in S4 are divided into three stages. For example, the first stage is: pressure resistance test. The micropores in the silica gel skeleton will affect the mechanical strength of the silica gel, resulting in the disadvantage of not being able to withstand pressure. Therefore, a pressure resistance test is required; the second stage is: sample comparison, comparing the selected products with qualified samples to ensure that the products have an effective surface area, so that the application field can be selected based on the surface area combined with the pore structure; the third stage is: chemical stability test, determining the pH value range of the silica gel filler, and selecting silica gel fillers with a wider pH value range to effectively solve the fluctuation of the separation effect;

[0061] A composite structure bonded silica high performance liquid chromatography filler with applications in industry, pharmaceuticals and molecular fields.

[0062] Embodiment 2:

[0063] In step 1, the specific method of the drying method is: first, the silicate is polymerized to form a sol. The sol is a liquid, which is conducive to spray drying. According to the spray principle, the silica sol is sprayed and dispersed, and then turned into a gel with vacuum drying. It is solidified in a hot air flow or a dispersant such as paraffin oil to obtain the final silica gel product.

[0064] The specific method of the polymerization reaction method in step 1 is: the silica sol in a gel state is encapsulated by a polymerization reaction in a silica sol dispersion system, and organic matter is removed by sintering to obtain porous silica microspheres.

[0065] The specific method of the two-gel method in step 1 is: using two catalysis-gels, using the hydrolysis and polycondensation principle of the silicon source, the hydrolysis rate of the silicon source is greater than its polycondensation rate, and it is easy to form a porous structure on the surface of the composite structure bonded silica gel high performance liquid chromatography filler. On the contrary, it is easy to form a non-porous gel-like structure, and a composite structure bonded silica gel high performance liquid chromatography filler in two structural states can be prepared. The silica gel microspheres made of the silicon source body are fixed and nucleated. This process is used to control the particle size of the silica gel filler and is carried out under acidic conditions. Template substances can be added during the process to regulate the silica gel pore structure;

[0066] The second catalysis is to age the silica gel filler under alkaline conditions to fix the silica gel filler. The two-step hydrolysis and polycondensation can effectively support silica gel HPLC fillers with the same average particle size.

[0067] The specific method of surface chemical modification in step 2 is: bonding the organic compound to the silica surface through chemical reaction, and reacting with the free silanol groups on the silica surface. In the overall modification, on the basis of surface chemical modification, alkoxysilane is added to improve stability and allow the organic compound to be evenly distributed on the surface of the silica filler.

[0068] The specific method of the auxiliary polymerization coating method in step 2 is: in the process of modification, inorganic materials will be added to make the shape of the filler more regular, and to improve the mechanical strength, improve the shielding property of the surface of the silica gel filler, and reduce the dissolution of the silica gel filler during use.

[0069] The specific method of electrostatic shielding in step 2 is: using the principle of electrostatic shielding, the amine molecules in the silica gel filler can be positively charged, thereby repelling positively charged solutes, which is complementary to the above-mentioned polymerization coating method to further shield the excess silanol groups on the surface of the silica gel filler.

[0070] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a composite structure bonded silica gel high performance liquid chromatography filler, characterized in that: The preparation method comprises the following steps: (1) Selecting a silicon source, generally using ethyl orthosilicate as the base silicon source, and preparing it by a drying method, a polymerization reaction method, a double gel method, etc.; (2) Silica gel modification, which combines surface chemical modification and overall modification to change the traditional commonly used surface modification method, so that the structure can better bond with the silica gel surface and have better stability. At the same time, the auxiliary polymerization coating method is used to effectively cover the residual silanol groups on the silica gel surface in the form of cross-linking; (3) Electrostatic shielding can make silica gel carry a positive charge, which will repel positively charged solutes and protect the solute molecules from ion exchange with the dissociated silanol groups, so that the coagulant solvent in the silica gel can be effectively distributed, improving the selectivity and further shielding the silanol groups, so that the corresponding molecules and compounds can react with the silica gel surface in a directional manner, which is conducive to the composite structure bonded silica gel for biological separation and analysis.

2. The method for preparing a composite structure bonded silica gel high performance liquid chromatography filler according to claim 1, characterized in that: In step (1), the specific method of the drying method is: first, silicate is polymerized to form a sol, and the sol is a liquid, which is conducive to spray drying. According to the spray principle, the silica sol is sprayed and dispersed, and then turned into a gel by vacuum drying.

3. The method for preparing a composite structure bonded silica gel high performance liquid chromatography filler according to claim 1, characterized in that: The specific method of the polymerization reaction method in step (1) is as follows: the silica sol in a gel state is encapsulated by a polymerization reaction in a silica sol dispersion system, and organic matter is removed by sintering to obtain porous silica microspheres.

4. Claims for a composite structure bonded silica gel high performance liquid chromatography according to claim 1 A method for preparing a filler, characterized in that: The specific method of the double gel method in step (1) is: using double catalysis-gel, using the hydrolysis and polycondensation principle of the silicon source, the silica gel microspheres made of the silicon source body are fixed and nucleated. This process is used to control the particle size of the silica gel filler and is carried out under acidic conditions. Template substances can be added during the process to regulate the silica gel pore structure; The second catalysis is to age the silica gel filler under alkaline conditions to fix the silica gel filler. The two-step hydrolysis and polycondensation can effectively support silica gel HPLC fillers with the same average particle size.

5. The method for preparing a composite structure bonded silica gel high performance liquid chromatography filler according to claim 1, characterized in that: The specific method of surface chemical modification in step (2) is: bonding the organic compound to the silica surface through a chemical reaction, and reacting with the free silanol groups on the silica surface. In the overall modification, on the basis of surface chemical modification, alkoxysilane is added to improve stability and allow the organic compound to be evenly distributed on the surface of the silica filler.

6. The method for preparing a composite structure bonded silica gel high performance liquid chromatography filler according to claim 1, characterized in that: The specific method of the auxiliary polymerization coating method in step (2) is: during the modification process, inorganic materials are added to make the shape of the filler more regular, and to improve the mechanical strength, improve the shielding property of the surface of the silica gel filler, and reduce the dissolution of the silica gel filler during use.

7. The method for preparing a composite structure bonded silica gel high performance liquid chromatography filler according to claim 1, characterized in that: The specific method of electrostatic shielding in step (2) is: using the principle of electrostatic shielding, the amine molecules in the silica gel filler can be positively charged, so that the positively charged solutes can be repelled, which is complementary to the above-mentioned polymerization coating method to further shield the silica gel filler. Excess silanol groups on the surface of the material.

8. An application of a composite structure bonded silica gel high performance liquid chromatography filler as claimed in any one of claims 1 to 7, characterized in that: As the application of composite structure bonded silica HPLC filler in industrial, chemical and biological separation analysis, the composite structure bonded silica HPLC filler products are first selected and the preferred products are tested, and finally applied to different fields.

9. The use of a composite structure bonded silica gel high performance liquid chromatography filler according to claim 8, characterized in that: The specific steps for selecting the composite structure bonded silica gel high performance liquid chromatography filler product are as follows: S1: select products according to their morphology, which are divided into amorphous silica gel fillers and spherical silica gel fillers, both of which can be used in industry, with spherical silica gel fillers being preferred, and amorphous silica gel fillers being alternatives based on cost budget; S2: according to the pore structure, they are divided into intervention pores, large pores, and extra-large pores, and the application range is selected according to the numerical range of the pore structure; S3: within the intervention pore range, select industrial preparation, secondly, within the large pore range, select separation and pharmaceutical manufacturing, and thirdly, within the extra-large pore range, select the separation of polymers and biomacromolecules; S4: perform quality tests on the selected high-quality products.

10. The use of a composite structure bonded silica gel high performance liquid chromatography filler according to claim 9, characterized in that: The specific steps of the quality test described in S4 are divided into three stages, such as the first stage: pressure test, the micropores in the silica gel skeleton will affect the mechanical strength of the silica gel, resulting in the disadvantage of not being able to withstand pressure, therefore, a pressure test is required; the second stage: sample comparison, comparing the selected product with the qualified sample to ensure that the product has an effective surface area, so that the application field can be selected based on the surface area combined with the pore structure; the third stage: chemical stability test, determining the pH value range of the silica gel filler, selecting a silica gel filler with a wider pH value range, and effectively solving the fluctuation of the separation effect; Application of the composite structure bonded silica gel high performance liquid chromatography filler as described in any one of claims 8 to 10 in industrial, pharmaceutical and molecular fields.

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