A bidentate ligating amide embedded c 18 Process for the preparation of silica gel chromatography column packings and use thereof

Abstract

The application relates to a bidentate chelating amide embedded C 18 Preparation method of silica gel column filler and application thereof. The preparation method of the filler comprises the following steps: activating silica gel balls, embedding bidentate amide into C 18 alkane synthesis, bonding reaction steps. Different from the prior art, the bidentate amide embedded C 18 alkane is synthesized through nucleophilic substitution, the bidentate amide embedded C 18 alkane is bonded to the surface of silica gel, one functional group is connected to the surface of silica gel by two silicon-oxygen bonds at the same time, the hydrolysis stability of the silica gel is improved, the stationary phase density is increased, and the surface carbon loading is increased. The preparation method has the advantages of simple operation, mild reaction condition, specificity and high grafting rate. The chromatographic column can be hydrophilic and can be used under a wide pH value mobile phase, has good separation performance for different polar compounds, and is suitable for the field of drug detection.

Description

Technical Field

[0001] This invention relates to the production and application of liquid chromatography columns, and particularly to a bidentate bonded amide intercalation C... 18 Preparation methods and applications of silica gel chromatography column packing materials. Background Technology

[0002] Reversed-phase liquid chromatography is currently the most widely used chromatographic mode for separation and analysis, with octadecyl-modified silica gel stationary phase (C164- ... 18 Alkane (C) is a classic reversed-phase chromatography packing material with long alkane chains. It achieves the separation of most nonpolar to moderately polar compounds through hydrophobic interactions between the hydrophobic stationary phase and the solute. However, when separating polar compounds, traditional C14 chromatography often employs methods such as reducing the proportion of organic phase in the mobile phase, using pure water as the mobile phase, or using an extreme pH as the mobile phase. 18 The stationary phase exhibits significant limitations. For example, when a high proportion of water is used as the mobile phase, C... 18 Long chains are prone to collapse, leading to pore blockage and excessive pressure; low pH (pH < 2) mobile phases can easily cause bonded phase detachment, resulting in a sharp drop in column efficiency and poor peak shape; high pH (pH > 8) mobile phases cause the silica skeleton to dissolve, the column bed to collapse, the column dead volume to increase, resulting in peak bifurcation and severe tailing; in addition, when analyzing basic compounds, tailing is prone to occur, and even if alkylation reagents are used for end-capping, there are still unreacted residual silanol groups, which seriously affect the separation process.

[0003] Compared to traditional C 18 Chromatographic column, polar intercalation C 18 The stationary phase can significantly reduce hydrophobicity and the activity of residual silanol groups. In the analysis of basic and acidic compounds, the stationary phase interacts with the sample in multiple ways, leading to better separation of the target analyte. However, existing polar-intercalated C... 18 Stationary phases also generally suffer from problems such as complex preparation processes, complex reaction conditions, and low grafting rates. Summary of the Invention

[0004] In view of the above problems, the present invention provides a bidentate bonded amide intercalation C 18 A method for preparing silica gel chromatography column packing material, which synthesizes bidentate amide chimeric C via nucleophilic substitution. 18 Alkanes, with bidentate amides intercalated with C 18 Alkanes are bonded to the surface of silica gel. This preparation method is simple, reliable, and operates under mild conditions, making it suitable for industrial application.

[0005] The first aspect of the present invention provides a bidentate bonded amide intercalation C 18 The preparation method of silica gel chromatography column packing includes the following steps:

[0006] Activation of silica spheres: The surface of silica spheres is activated with acid to obtain activated silica spheres with hydroxyl groups;

[0007] Bis-dentamide intercalation C 18 Alkane synthesis: A bidentate reagent and an octadecane reagent were synthesized in a first solvent to obtain a first mixture. After concentrating and evaporating the first mixture, a bidentate amide with C-intercalation was obtained. 18 Bonded phase, i.e., bidentate amide intercalated into C 18 Alkanes;

[0008] Bonding reaction: The activated silica spheres and the bidentate amide are embedded in C 18 The bonded phase is immersed in a second solvent for bonding to obtain a bidentate amide intercalated with C. 18 Silica gel chromatography column packing material.

[0009] Unlike existing technologies, this invention synthesizes bidentate amide chimeric C via nucleophilic substitution. 18 Alkanes, with bidentate amides intercalated with C 18 Alkane bonding to the silica gel surface, with a functional group simultaneously attached to the silica gel surface via two silicon-oxygen bonds, improves the hydrolytic stability of the silica gel, increases the density of the stationary phase, and enhances the surface carbon loading. This preparation method is simple to operate, has mild reaction conditions, is specific, and has a high grafting rate.

[0010] Furthermore, the silica spheres have a particle size of 5 μm and a pore size of 11-12 nm; the silica spheres and the bidentate amide are embedded in C 18 The mass ratio of the bonded phases is 1:2~10.

[0011] Furthermore, in the silica sphere activation step, the silica spheres are ultrasonically dispersed with 5–10 mol / L hydrochloric acid, stirred at 105–110°C for 2–48 h, washed with water, and dried at 100–160°C to obtain activated silica spheres with hydroxyl groups. This activation step removes trace metal ions adsorbed on the surface of the spherical silica spheres and also fully exposes the silanol groups on the surface of the spherical silica spheres, increasing the reaction yield.

[0012] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, the bidentate reagent is bis[3-(trimethoxysilyl)]propylamine, the octadecane reagent is stearyl chloride, and the first solvent is tetrahydrofuran.

[0013] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, the molar ratio of bis[3-(trimethoxysilyl)]propylamine to stearoyl chloride is 1:30 to 30:1.

[0014] Furthermore, the bidentate amide is embedded in C 18In the alkane synthesis step, triethylamine is also added as a catalyst.

[0015] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, the bis[3-(trimethoxysilyl)]propylamine, the catalyst triethylamine, and the stearoyl chloride are sequentially added to the tetrahydrofuran solvent and stirred in an ice-water bath; then the temperature is raised to 20~30℃ for synthesis.

[0016] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, tetrahydrofuran and bis[3-(trimethoxysilyl)]propylamine were added under an ice-water bath and stirred for 1–30 min. Triethylamine was then added, and stirring continued under an ice-water bath for another 1–30 min. Finally, stearoyl chloride was added and stirred for 1–30 min. The resulting mixture was then heated to room temperature and reacted for 1–48 h. The reaction product was then obtained by vacuum rotary evaporation to yield a bidentate amide intercalated at C10. 18 Alkanes.

[0017] Furthermore, in the bonding reaction step, the second solvent is toluene, and the bonding reaction is carried out at a temperature of 50~110℃ under nitrogen protection for 2~48 h.

[0018] Furthermore, in the bonding reaction step, the activated silica spheres are ultrasonically suspended in toluene, and then the bidentate amide intercalating C is added. 18 The bonded phase was subjected to a bonding reaction at 50–110 °C under nitrogen protection for 2–48 h. The resulting mixture was filtered, washed, and vacuum dried at 100–160 °C for 12–24 h to obtain a bidentate bonded amide intercalated with C. 18 Silica gel chromatography column packing material.

[0019] A second aspect of the present invention provides a silica gel chromatography column, wherein the silica gel chromatography column is packed with silica gel chromatography column packing material prepared by the preparation method described in the first aspect of the present invention.

[0020] The third aspect of this invention provides the application of the silica gel chromatographic column described in the second aspect of this invention in drug detection.

[0021] Unlike existing technologies, bidentate-bonded amides are embedded in C 18 Alkanes, by simultaneously attaching a functional group to the silica gel surface via two silicon-oxygen bonds, improve the hydrolytic stability of the silica gel, increase the density of the stationary phase, and thus enhance the surface carbon loading. On one hand, because the two sites are tightly bonded to the silica gel surface, a cross-linked protective layer is formed between adjacent silicon-oxygen bonds, preventing the silica matrix from reacting with OH groups even under high pH conditions. -It dissolves directly; furthermore, it has a longer lifespan under low pH conditions. On the other hand, it reduces the exposure of silanol groups on the silica gel surface, minimizing secondary interactions between silanol groups and basic compounds, thus significantly improving peak tailing. The column is both hydrophilic and usable under a wide pH range of mobile phases, exhibiting excellent separation performance for compounds of varying polarities, making it suitable for pharmaceutical detection.

[0022] The above description of the invention is merely an overview of the technical solution of the present invention. In order to enable those skilled in the art to better understand the technical solution of the present invention and to implement it based on the textual description of the specification, and to make the above-mentioned objectives and other objectives, features and advantages of the present invention easier to understand, the following description is provided in conjunction with the specific embodiments and accompanying drawings of the present invention. Attached Figure Description

[0023] The accompanying drawings are only used to illustrate the principles, implementation methods, applications, features, and effects of specific embodiments of the present invention and other related contents, and should not be considered as limitations on the present invention.

[0024] In the accompanying drawings of the instruction manual:

[0025] Figure 1 For bidentate bonded amides intercalated with C 18 A schematic diagram of the preparation method of silica gel chromatography column packing material;

[0026] Figure 2 This is a chromatogram for the hydrophilicity test of the chromatographic column;

[0027] Figure 3 Chromatogram for low-pH hydrolytic stability test of chromatographic column;

[0028] Figure 4 This is a chromatogram for the high pH hydrolysis stability test of the chromatographic column;

[0029] Figure 5 Chromatogram and peak table of paeoniflorin separation by chromatographic column;

[0030] Figure 6 Chromatograms and peak tables for the separation of Xiaojianzhong compound by chromatographic column. Detailed Implementation

[0031] To illustrate the possible application scenarios, technical principles, implementable specific solutions, and achievable objectives and effects of this invention in detail, the following description, in conjunction with the listed specific embodiments and accompanying drawings, provides a detailed explanation. The embodiments described herein are merely illustrative of the technical solutions of this invention and are therefore intended only as examples, not as limiting the scope of protection of this invention.

[0032] In this document, the term "embodiment" means that a specific feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of the invention. The term "embodiment" appearing in various places throughout the specification does not necessarily refer to the same embodiment, nor does it specifically limit its independence or connection with other embodiments. In principle, in this invention, as long as there are no technical contradictions or conflicts, the technical features mentioned in each embodiment can be combined in any way to form corresponding implementable technical solutions.

[0033] Unless otherwise defined, the technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains; the use of related terms herein is merely for the purpose of describing particular embodiments and is not intended to limit the invention.

[0034] In the description of this invention, the term "and / or" is used to describe the logical relationship between objects, indicating that three relationships can exist. For example, A and / or B means: A exists, B exists, and A and B exist simultaneously. Additionally, the character " / " generally indicates that the preceding and following objects have an "or" logical relationship.

[0035] In this invention, terms such as “first” and “second” are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any actual quantity, hierarchy, or order between these entities or operations.

[0036] Without further limitations, the use of terms such as “comprising,” “including,” “having,” or other similar expressions in this invention is intended to cover non-exclusive inclusion, which does not exclude the presence of additional elements in a process, method, or product that includes the stated elements, such that a process, method, or product that includes a list of elements may include not only those defined elements but also other elements not expressly listed, or elements inherent to such a process, method, or product.

[0037] Similar to the understanding in the Examination Guidelines, in this invention, expressions such as "greater than," "less than," and "exceeding" are understood to exclude the stated number; expressions such as "above," "below," and "within" are understood to include the stated number. Furthermore, in the description of the embodiments of this invention, "multiple" means two or more (including two), and similar expressions related to "multiple" are also understood in this way, such as "multiple groups" and "multiple times," unless otherwise explicitly specified.

[0038] The first aspect of the present invention provides a bidentate bonded amide intercalation C 18 The preparation method of silica gel chromatography column packing includes the following steps:

[0039] Activation of silica spheres: The surface of silica spheres is activated with acid to obtain activated silica spheres with hydroxyl groups;

[0040] Bis-dentamide intercalation C 18 Alkane synthesis: A bidentate reagent and an octadecane reagent are synthesized in a first solvent to obtain a first mixture. After concentrating and evaporating the first mixture, a bidentate amide with C-intercalation is obtained. 18 Bonded phase, i.e., bidentate amide intercalated into C 18 Alkanes;

[0041] Bonding reaction: The activated silica spheres and the bidentate amide are embedded in C 18 The bonded phase is immersed in a second solvent for bonding to obtain a bidentate amide intercalated with C. 18 Silica gel chromatography column packing material.

[0042] Unlike existing technologies, this invention synthesizes bidentate amide chimeric C via nucleophilic substitution. 18 Alkanes, with bidentate amides intercalated with C 18 Alkane bonding to the silica gel surface, with a functional group simultaneously attached to the silica gel surface via two silicon-oxygen bonds, improves the hydrolytic stability of the silica gel, increases the density of the stationary phase, and enhances the surface carbon loading. This preparation method is simple to operate, has mild reaction conditions, is specific, and has a high grafting rate.

[0043] Furthermore, the silica spheres have a particle size of 5 μm and a pore size of 11-12 nm; the silica spheres and the bidentate amide are embedded in C 18 The mass ratio of the bonded phases is 1:2~10.

[0044] Furthermore, in the silica sphere activation step, the silica spheres are ultrasonically dispersed with 5–10 mol / L hydrochloric acid, stirred at 105–110°C for 2–48 h, washed with water, and dried at 100–160°C to obtain activated silica spheres with hydroxyl groups. This activation step removes trace metal ions adsorbed on the surface of the spherical silica spheres and also fully exposes the silanol groups on the surface of the spherical silica spheres, increasing the reaction yield.

[0045] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, the bidentate reagent is bis[3-(trimethoxysilyl)]propylamine, the octadecane reagent is stearyl chloride, and the first solvent is tetrahydrofuran.

[0046] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, the molar ratio of bis[3-(trimethoxysilyl)]propylamine to stearoyl chloride is 1:30 to 30:1.

[0047] Furthermore, the bidentate amide is embedded in C 18In the alkane synthesis step, triethylamine is also added as a catalyst.

[0048] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, the bis[3-(trimethoxysilyl)]propylamine, the catalyst triethylamine, and the stearoyl chloride are sequentially added to the tetrahydrofuran solvent and stirred in an ice-water bath; then the temperature is raised to 20~30℃ for synthesis.

[0049] Furthermore, the bidentate amide is embedded in C 18 In the alkane synthesis step, tetrahydrofuran and bis[3-(trimethoxysilyl)]propylamine were added under an ice-water bath and stirred for 1–30 min. Triethylamine was then added, and stirring continued under an ice-water bath for another 1–30 min. Finally, stearoyl chloride was added and stirred for 1–30 min. The resulting mixture was then heated to room temperature and reacted for 1–48 h. The reaction product was then obtained by vacuum rotary evaporation to yield a bidentate amide intercalated at C10. 18 Alkanes.

[0050] Furthermore, in the bonding reaction step, the second solvent is toluene, and the bonding reaction is carried out at a temperature of 50~110℃ under nitrogen protection for 2~48 h.

[0051] Furthermore, in the bonding reaction step, the activated silica spheres are ultrasonically suspended in toluene, and then the bidentate amide intercalating C is added. 18 The bonded phase was subjected to a bonding reaction at 50–110 °C under nitrogen protection for 2–48 h. The resulting mixture was filtered, washed, and vacuum dried at 100–160 °C for 12–24 h to obtain a bidentate bonded amide intercalated with C. 18 Silica gel chromatography column packing material.

[0052] A second aspect of the present invention provides a silica gel chromatography column, wherein the silica gel chromatography column is packed with silica gel chromatography column packing material prepared by the preparation method described in the first aspect of the present invention.

[0053] The third aspect of this invention provides the application of the silica gel chromatographic column described in the second aspect of this invention in drug detection.

[0054] Unlike existing technologies, bidentate-bonded amides are embedded in C 18 Alkanes, by simultaneously attaching a functional group to the silica gel surface via two silicon-oxygen bonds, improve the hydrolytic stability of the silica gel, increase the density of the stationary phase, and thus enhance the surface carbon loading. On one hand, because the two sites are tightly bonded to the silica gel surface, a cross-linked protective layer is formed between adjacent silicon-oxygen bonds, preventing the silica matrix from reacting with OH groups even under high pH conditions. -It dissolves directly; furthermore, it has a longer lifespan under low pH conditions. On the other hand, it reduces the exposure of silanol groups on the silica gel surface, minimizing secondary interactions between silanol groups and basic compounds, thus significantly improving peak tailing. The column is both hydrophilic and usable under a wide pH range of mobile phases, exhibiting excellent separation performance for compounds of varying polarities, making it suitable for pharmaceutical detection.

[0055] Example 1: Bidentate bonded amide intercalation C 18 Preparation of silica gel chromatography column packing

[0056] The preparation process of the filler is as follows: Figure 1 As shown, it includes:

[0057] Activation of silica spheres: Weigh 5 g of silica spheres, stir and react with 6 mol / L HCl at 110°C for 24 h, filter, wash with pure water until neutral, and then dry at 150°C for 12 h to obtain activated silica spheres with hydroxyl groups.

[0058] Bis-dentamide intercalation C 18 Alkane synthesis: 50 mL of tetrahydrofuran, 6 mL of bis[3-(trimethoxysilyl)]propylamine, 3 mL of triethylamine, and 3 mL of stearoyl chloride were added in an ice-water bath and stirred for 30 min. The mixture was then raised to room temperature (20-30 °C) and reacted for 48 h. After the reaction was completed, the mixture was concentrated using a vacuum rotary evaporator to obtain a bidentate amide intercalated with C. 18 Bonded phase.

[0059] Bonding reaction: Weigh 3 g of activated silica gel spheres, use toluene as solvent, add 7.5 g of bidentate bonding amide to intercalate C. 18 The bonded phase was heated to reflux and reacted under nitrogen protection for 24 h. After the reaction, it was washed successively with methanol, 50% methanol-water mixture, and methanol, and then dried under vacuum at 100°C for 12 h to obtain a bidentate bonded amide intercalated with C as shown in Formula I. 18 Silica gel chromatography column packing material.

[0060]

[0061] Formula I

[0062] Example 2 Hydrophilicity Test

[0063] The bidentate-bonded amide prepared in Example 1 is used to embed C 18 The silica gel chromatographic stationary phase was packed using a high-pressure homogenization method. The column was 250 mm long and 4.6 mm in inner diameter. The packing conditions were as follows: packing pressure 3000-7000 psi, homogenizer: isopropanol, and finally replaced with methanol for 30 min. Hydrophilicity testing was performed in reversed-phase mode.

[0064] Chromatographic conditions: 10 mmol / L phosphoric acid water as mobile phase; detection wavelength: 254 nm; injection volume: 10 μL; column temperature: 30 ℃; flow rate: 1.0 min / mL; separation targets: cytosine and uracil; testing cycle: continuous testing for one month.

[0065] Separation chromatogram as follows Figure 2 As shown, bidentate bonded amides are embedded in C 18 After one month of continuous testing on the silica gel stationary column, uracil and cytosine still exhibited good peak shapes and stable retention times, indicating that the bidentate-bonded amide intercalation into C... 18 The silica gel chromatography stationary column did not collapse when using 100% aqueous phase as mobile phase because the embedded amide groups improve the water resistance of the stationary phase.

[0066] Example 3 Hydrolysis Stability Test

[0067] The bidentate-bonded amide prepared in Example 1 is used to embed C 18 The silica gel chromatographic stationary phase was packed using a high-pressure homogenization method. The column was 250 mm long and had an inner diameter of 4.6 mm. Hydrolytic stability tests were performed on the column in reversed-phase mode.

[0068] Chromatographic conditions: For low pH testing, the mobile phase was acetonitrile:1% TFA aqueous solution (50:50, v / v, pH 1.0), the flow rate was 1.0 mL / min, the column temperature was 50°C, the detection wavelength was 254 nm, the injection volume was 10 μL, and the probe was toluene; for high pH testing, the mobile phase was acetonitrile-20 mmol / L triethylamine aqueous solution (50:50, v / v, pH 12), the flow rate was 1.0 mL / min, the column temperature was 60°C, the detection wavelength was 254 nm, the injection volume was 10 μL, and the probe was naphthalene; the testing period was one month.

[0069] The separation chromatograms are as follows: Figure 3 , Figure 4 As shown; bidentate bonded amide intercalation C 18 The silica gel chromatographic stationary phase exhibited good stability even after continuous storage at extreme pH conditions for 30 days, indicating that the bidentate bonded C-type intercalation of this invention... 18 The stationary phase has a stable structure and can be used in a wide range of mobile phases with varying pH values.

[0070] Example 4: Determination and Analysis of the Content of Xiaojianzhong Compound

[0071] The bidentate-bonded amide prepared in Example 1 is used to embed C 18The silica gel chromatographic stationary phase was packed using a high-pressure homogenization method. The column was 250 mm long and 4.6 mm in inner diameter. The content of Xiaojianzhong compound was determined in reversed-phase mode.

[0072] Chromatographic conditions: The mobile phase was methanol-0.3% phosphoric acid solution (25:75); the detection wavelength was 230 nm. The target for separation was paeoniflorin, and the theoretical plate number calculated based on the paeoniflorin peak should be no less than 1500. The sample preparation method was in accordance with the 2025 edition of the Pharmacopoeia of the People's Republic of China.

[0073] The separation chromatograms are as follows: Figure 5 , Figure 6 As shown; bidentate bonded amide intercalation C 18 The content of paeoniflorin in Xiaojianzhong compound was determined by silica gel chromatography stationary phase. The peak shape of paeoniflorin was good and the theoretical plate number was greater than 1500, which is suitable for the determination of this compound.

[0074] In summary, the bidentate-bonded amide intercalated with C prepared in this invention... 18 Silica gel chromatography stationary phases have a novel structure and are easy to operate. They can be applied to both 100% aqueous systems and mobile phase systems with pH (1~12), and are suitable for the separation of most polar compounds.

[0075] Finally, it should be noted that although the above embodiments have been described in the description and drawings of this invention, this should not limit the scope of patent protection of this invention. Any technical solutions that are based on the essential concept of this invention, utilize the content described in the description and drawings of this invention to make equivalent structural or procedural substitutions or modifications, as well as the direct or indirect application of the technical solutions of the above embodiments to other related technical fields, are all included within the scope of patent protection of this invention.

Claims

1. A bidentate bonded amide intercalating C 18 A method for preparing silica gel chromatography column packing material, characterized in that, Includes the following steps: Activation of silica spheres: The surface of silica spheres is activated with acid to obtain activated silica spheres with hydroxyl groups; Bis-dentamide intercalation C 18 Alkane synthesis: A bidentate reagent and an octadecane reagent are synthesized in a first solvent to obtain a first mixture. After concentrating and evaporating the first mixture, a bidentate amide with C-intercalation is obtained. 18 Bonded phase, i.e., bidentate amide intercalated into C 18 Alkanes; Bonding reaction: The activated silica spheres and the bidentate amide are embedded in C 18 The bonded phase is immersed in a second solvent for bonding to obtain a bidentate amide intercalated with C. 18 Silica gel chromatography column packing material.

2. The preparation method according to claim 1, characterized in that, The silica spheres have a particle size of 5 μm and a pore size of 11-12 nm; the silica spheres and the bidentate amide are embedded in C 18 The mass ratio of the bonded phases is 1:2~10.

3. The preparation method according to claim 1, characterized in that, In the activated silica sphere step, the silica spheres are ultrasonically dispersed with 5-10 mol / L hydrochloric acid, stirred at 105-110℃ for 2-48 h, washed with water, and dried at 100-160℃ to obtain activated silica spheres with hydroxyl groups.

4. The preparation method according to claim 1, characterized in that, The bidentate amide intercalated C 18 In the alkane synthesis step, the bidentate reagent is bis[3-(trimethoxysilyl)]propylamine, the octadecane reagent is stearyl chloride, and the first solvent is tetrahydrofuran.

5. The preparation method according to claim 3, characterized in that, The bidentate amide intercalated C 18 In the alkane synthesis step, the molar ratio of bis[3-(trimethoxysilyl)]propylamine to stearoyl chloride is 1:30 to 30:

1.

6. The preparation method according to claim 3, characterized in that, The bidentate amide intercalated C 18 In the alkane synthesis step, triethylamine is also added as a catalyst.

7. The preparation method according to claim 6, characterized in that, The bidentate amide intercalated C 18 In the alkane synthesis step, the bis[3-(trimethoxysilyl)]propylamine, the catalyst triethylamine, and the stearoyl chloride are sequentially added to the tetrahydrofuran solvent and stirred in an ice-water bath; then the temperature is raised to 20~30℃ for synthesis.

8. The preparation method according to claim 1, characterized in that, In the bonding reaction step, the second solvent is toluene, and the bonding reaction is carried out at a temperature of 50~110℃ under nitrogen protection for 2~48 h.

9. A silica gel chromatography column, characterized in that, The silica gel chromatographic column is packed with silica gel chromatographic column packing material prepared by any one of claims 1-8.

10. The application of the silica gel chromatographic column of claim 9 in pharmaceutical detection.

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