[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN113274993A - Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs - Google Patents

Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs Download PDF

Info

Publication number
CN113274993A
CN113274993A CN202110570901.4A CN202110570901A CN113274993A CN 113274993 A CN113274993 A CN 113274993A CN 202110570901 A CN202110570901 A CN 202110570901A CN 113274993 A CN113274993 A CN 113274993A
Authority
CN
China
Prior art keywords
silica gel
chromatographic packing
porous silica
gel matrix
drying
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202110570901.4A
Other languages
Chinese (zh)
Inventor
宋志花
丁晶
毕毅
薛俊萍
柴佩君
刘金秋
王雅琦
张京秀
王玉朦
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yantai University
Original Assignee
Yantai University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yantai University filed Critical Yantai University
Priority to CN202110570901.4A priority Critical patent/CN113274993A/en
Publication of CN113274993A publication Critical patent/CN113274993A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26—Synthetic macromolecular compounds
    • B01J20/268—Polymers created by use of a template, e.g. molecularly imprinted polymers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
    • B01J20/28016—Particle form
    • B01J20/28021—Hollow particles, e.g. hollow spheres, microspheres or cenospheres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/282—Porous sorbents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/282—Porous sorbents
    • B01J20/283—Porous sorbents based on silica
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6095—Micromachined or nanomachined, e.g. micro- or nanosize

Landscapes

  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Nanotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

The invention belongs to the field of preparation of novel chromatographic packing, and discloses a preparation method of silica gel matrix chromatographic packing for chromatographic separation of strong-polarity drugs, which comprises the following steps: soaking silica gel in dilute nitric acid, and activating silicon hydroxyl on the surface of the silica gel; modifying double bonds on the surface of the silica gel; taking nucleoside drugs as template molecules to prepare a prepolymerization system; adding an initiator, a cross-linking agent and double-bond modified silica gel into the prepolymer system to perform imprinting polymerization reaction on the surface of the silica gel; and (3) eluting the silica gel obtained by the polymerization reaction by using an organic solvent, and removing template molecules to obtain the porous silica gel microspheres coated by the imprinted polymer. The invention combines the excellent selectivity of the molecular imprinting polymer with the properties of the silica gel material such as good pore structure, morphological characteristics, mechanical strength and the like, and controls the reaction conditions, so that the obtained chromatographic packing has high chromatographic separation column efficiency, high separation selectivity, good chromatographic peak symmetry and good separation reproducibility.

Description

Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs
Technical Field
The invention belongs to the field of preparation of novel chromatographic packing, and particularly relates to a preparation method of silica gel matrix chromatographic packing for chromatographic separation of strong-polarity drugs.
Background
Recently, with the continuous development of the biomedical industry, strong polar drugs (ginsenosides, nucleosides, sugar amino acids, alkaloids, and the like) attract extensive attention of researchers. The method has important significance for separating and analyzing strong-polarity drugs, improving the drug safety, analyzing the drug metabolic process and the like.
High performance liquid chromatography is most commonly used among many analytical detection methods for highly polar drugs today, however, it is difficult to efficiently separate them by conventional reverse phase chromatography columns. Therefore, the development of novel chromatographic separation materials is of great significance. At present, in order to solve the difficult problem of chromatographic separation of strong polar drugs, researchers have developed a series of novel chromatographic stationary phases, including novel chromatographic separation materials such as ionic liquid modified porous silica gel, carbon point modified porous silica gel, and polymer modified porous silica gel, for example, CN101757897A discloses a preparation method of chitosan oligosaccharide hydrophilic chromatographic stationary phases, which adopts "link chemistry" as a bonding reaction method to bond chitosan oligosaccharide, firstly, a terminal alkynyl is introduced on the surface of silica gel, and then, water, methanol or a mixture of these solvents is used as a reaction solvent to bond chitosan oligosaccharide modified with an azide group to the surface of silica gel, so as to obtain the chitosan oligosaccharide hydrophilic chromatographic stationary phase.
However, strongly polar drugs are still difficult to isolate efficiently. Therefore, the development of a novel liquid chromatography stationary phase with unique selectivity is of great significance for solving the problems.
Disclosure of Invention
In view of the above-mentioned disadvantages of the prior art, the present invention aims to provide a method for preparing a silica gel matrix chromatographic packing for chromatographic separation of strongly polar drugs.
In order to achieve the above purpose, the invention provides a preparation method of silica gel matrix chromatographic packing for chromatographic separation of strong polar drugs, which adopts the following technical scheme:
a method for preparing silica gel matrix chromatographic packing for separating strong polar drugs comprises the following steps:
1) silica gel selection and activation treatment: selecting porous silica gel microspheres with the particle size of 2-5 microns and the pore diameter of 15-30 nm as a carrier, soaking the porous silica gel microspheres by using dilute nitric acid with the mass fraction of 8-20%, washing the porous silica gel microspheres by using deionized water until the supernatant is neutral, washing the porous silica gel microspheres for 1-3 times by using absolute ethyl alcohol, and drying the porous silica gel microspheres;
2) silica gel surface modification double bond: adding an ethylene-based or propenyl silanization reagent into anhydrous toluene serving as a reaction medium, heating and refluxing for 8-24 h, washing with the anhydrous toluene and ethanol or methanol in sequence to obtain double-bond modified porous silica gel microspheres, and drying;
3) constructing a prepolymerization system: selecting one or more than two nucleoside drugs as template molecules, methacrylic acid or acrylamide as a functional monomer, and methanol, ethanol or acetonitrile as a pore-forming agent, and carrying out prepolymerization for 5-20 h at-5-10 ℃ to obtain a prepolymerization system;
4) polymerization reaction: slowly adding (one drop in liquid for about 1-5 seconds and 10 mg in solid for about 1-5 seconds) an initiator, a cross-linking agent and double-bond modified porous silica gel microspheres into a prepolymerization system, and reacting for 12-48 h at 30-70 ℃;
5) elution of template molecules: eluting the chromatographic separation material for 6-18 times by using an elution solvent, and drying for later use.
Preferably, in the step 1), a vacuum oven is adopted for drying, the temperature of the vacuum oven is set to be 50-100 ℃, and the time is 5-16 h.
Preferably, in the step 2), the toluene is adopted for washing for 2-5 times, and the methanol or ethanol is adopted for washing for 2-5 times.
Preferably, in the step 2), heating and drying are adopted, wherein the heating and drying temperature is 50-80 ℃, and the time is 6-16 h.
Preferably, in the step 4), the initiator is Azobisisobutyronitrile (AIBN); the crosslinking agent is one or more of trimethylolpropane Trimethacrylate (TRIM), Ethylene Glycol Dimethacrylate (EGDMA) or Diethylbenzene (DVB).
Preferably, the drying temperature in the step (5) is 50-70 ℃, and the time is 8-24 h.
The activation of the dilute nitric acid in the step 1) can effectively reduce metal impurities on the surface of the silica gel material, increase the content of silicon hydroxyl on the surface of the silica gel, and is beneficial to subsequent silanization modification and imprinting polymerization reaction on the surface of the porous silica gel.
In the step 2), modification of vinyl or propenyl is beneficial to guiding the imprinting polymerization reaction to be carried out on the surface of the porous silica gel orderly and controllably, and is beneficial to carrying out end capping treatment on silicon hydroxyl on the surface of the silica gel. Is beneficial to effectively improving the chromatographic separation performance of the material.
In the step 3), the nucleoside medicament can be obtained by market purchase, and can be made in China or imported, and three conditions are required to be met: 1) the stability of the molecule is good, and the molecule does not contain chemical groups which can prevent or influence polymerization reaction; 2) the molecule has carboxyl, hydroxyl and other groups capable of interacting with the functional monomer; 3) the template molecules have stronger rigidity in the imprinting process and are convenient to elute.
In some preferred embodiments of the present invention, the nucleoside drug is any one or a combination of zidovudine, lamivudine or adenosine.
In the step 3), methacrylic acid or acrylamide is used as a functional monomer, the methacrylic acid has carboxyl, the acrylamide has amino, and the methacrylic acid and the acrylamide can respectively act with template molecules to form a molecularly imprinted polymer cavity, and the formed polymers respectively have different charge characteristics, so that different separation effects can be realized.
The elution solvent in the step 5) is one or more than two of methanol, acetonitrile, acetic acid, formic acid, water and other solvents.
In the step 1), dilute nitric acid with the mass fraction of 8-20% is adopted to soak the porous silica gel microspheres for 1-5 hours.
The porous silica gel microspheres can be obtained commercially, and can be imported or made in China.
Compared with the prior art, the invention takes porous silica gel microspheres as a carrier, selects nucleoside drugs as template molecules, and provides a preparation method of a novel silica gel matrix chromatographic packing by means of a surface imprinting technology.
Drawings
Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:
FIG. 1 is a schematic diagram of the preparation of silica gel matrix chromatographic packing for strong polar drug separation of example 1;
FIG. 2 is a scanning electron microscope image of the porous silica gel microspheres (bare silica gel carrier) (a) used in example 1 and the surface imprinted chromatographic packing (b) of the nucleoside drug zidovudine;
FIG. 3 is an infrared spectrum of the porous silica gel microspheres (a), the surface imprinted chromatographic packing (b) of the nucleoside drug zidovudine and the non-imprinted material (c) used in example 1;
FIG. 4 is a chromatogram separation chart of C18 packing (a), nucleoside drug zidovudine surface imprinting chromatogram packing (b) and non-imprinting material for four nucleoside drugs (C);
FIG. 5 is the chromatogram separation chart of the chromatographic packing of surface imprinting of nucleoside drug zidovudine against ginsenosides.
FIG. 6 is the reproducibility of the continuous separation result of nucleoside drugs by the surface imprinted chromatographic packing of the nucleoside drugs zidovudine.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
Example 1
As shown in fig. 1, a method for preparing a silica gel matrix chromatographic packing for separating a strong polar drug comprises the following steps:
(1) silica gel selection and activation treatment: porous silica gel microspheres (purchased from FuJi, Japan) with the particle size of 5 mu m and the pore diameter of 20nm are selected as carriers, are soaked in dilute nitric acid with the mass fraction of 15% for 2 hours, are washed by deionized water until the supernatant is neutral, are washed by absolute ethyl alcohol for 3 times, and are dried in vacuum for 8 hours at the temperature of 55 ℃.
(2) Silica gel surface modification double bond: adding a silanization reagent gamma-methacryloxypropyltrimethoxysilane (gamma-MPS, KH570) into anhydrous toluene serving as a reaction medium, heating and refluxing for 24h, washing for 1 time by using the anhydrous toluene and washing for 3 times by using anhydrous ethanol in sequence to obtain double-bond modified porous silica gel microspheres, and heating for 8h and drying at the temperature of 55 ℃.
(3) Constructing a prepolymerization system: zidovudine is selected as a template molecule, methacrylic acid is taken as a functional monomer, methanol is taken as a pore-foaming agent, and prepolymerization is carried out for 12h at 4 ℃.
(4) Polymerization reaction: slowly adding an initiator Azobisisobutyronitrile (AIBN), a crosslinking agent Ethylene Glycol Dimethacrylate (EGDMA) and double-bond modified (double-bond functionalized) porous silica gel microspheres into a prepolymerization system under the reaction condition of 50 ℃ for 12 hours, then continuously heating to 60 ℃ and continuously reacting for 24 hours;
(5) elution of template molecules: eluting the solvent with a methanol-formic acid mixed solution with a ratio of 9:1, washing the material for 6 times, washing the material with absolute ethanol for 2 times, and drying at 55 ℃ for 8h for later use.
The characterization result shows that the particle size of the obtained material is uniformly distributed at 5 μm, and the material has a better spherical shape (see figure 2); the infrared characterization result proves that the molecularly imprinted polymer is successfully modified on the surface of the porous silica gel (see figure 3). The obtained nucleoside medicament zidovudine surface imprinted chromatographic packing can realize baseline separation on four nucleoside medicaments (1-adenine, 2-acyclovir, 3-stavudine and 4-zidovudine), the separation column efficiency on four targets is respectively 15,300, 19,300, 17,100 and 12,600 theoretical plate number per meter, and the separation result is superior to that of C18 and non-imprinted materials (see figure 4). In addition, the obtained imprinted material can realize baseline separation on ginsenoside compounds, see fig. 5, wherein the separation column efficiency on ginsenoside Rb1 can reach 8,600 theoretical plate number per meter; after the obtained imprinted material is continuously used for 17 days, the column effect, the retention factor, the peak area, the chromatographic peak shape symmetry and the like are good, and the good stability is shown, which is shown in figure 6.
Example 2
A method for preparing silica gel matrix chromatographic packing for separating strong polar drugs comprises the following steps:
(1) silica gel selection and activation treatment: porous silica gel microspheres (purchased from FuJi, Japan) with the particle size of 5 mu m and the pore diameter of 15nm are selected as carriers, the porous silica gel microspheres are soaked by dilute nitric acid with the mass fraction of 10 percent for 1.5h, then the porous silica gel microspheres are washed by deionized water until the supernatant is neutral, and then the porous silica gel microspheres are washed by absolute ethyl alcohol for 2 times and are dried in vacuum for 8h at the temperature of 60 ℃.
(2) Silica gel surface modification double bond: anhydrous toluene is taken as a reaction medium, a silanization reagent gamma-methacryloxypropyltrimethoxysilane (gamma-MPS) is added, heating and refluxing are carried out for 12 hours, the anhydrous toluene is adopted for washing for 2 times, and the anhydrous ethanol is adopted for washing for 2 times in sequence, so that double-bond modified porous silica gel microspheres are obtained, and the double-bond modified porous silica gel microspheres are heated for 8 hours and dried at the temperature of 60 ℃.
(3) Constructing a prepolymerization system: zidovudine and lamivudine are selected as double-template molecules, acrylamide is used as a functional monomer, acetonitrile is used as a pore-foaming agent, and prepolymerization is carried out for 16h at the temperature of 8 ℃.
(4) Polymerization reaction: slowly adding an initiator Azobisisobutyronitrile (AIBN), a cross-linking agent Diethylbenzene (DVB) and double-bond functionalized porous silica gel microspheres into a prepolymerization system, reacting for 15 hours under the condition of 58 ℃, then continuously heating to 60 ℃, and continuously reacting for 18 hours; (5) elution of template molecules: eluting the solvent with ethanol-acetic acid mixed solution at a ratio of 8:3, washing the material for 15 times, washing the material with anhydrous ethanol for 1 time, and drying at 65 ℃ for 18h for later use.
Example 3
A method for preparing silica gel matrix chromatographic packing for separating strong polar drugs comprises the following steps:
(1) silica gel selection and activation treatment: porous silica gel microspheres (purchased from Tianjin Borui) with the particle size of 3 mu m and the pore diameter of 16nm are selected as carriers, are soaked for 1h by using dilute nitric acid with the mass fraction of 20 percent, are washed by deionized water until the supernatant is neutral, are washed by absolute ethyl alcohol for 1 time, and are dried in vacuum for 5h at the temperature of 100 ℃.
(2) Silica gel surface modification double bond: adding a silanization reagent gamma-methacryloxypropyltrimethoxysilane (gamma-MPS) into anhydrous toluene serving as a reaction medium, heating and refluxing for 8 hours, washing for 5 times by using the anhydrous toluene and washing for 5 times by using anhydrous ethanol to obtain double-bond modified porous silica gel microspheres, and heating for 7 hours at 70 ℃ for drying.
(3) Constructing a prepolymerization system: zidovudine and adenosine are selected as double-template molecules, acrylamide is used as a functional monomer, acetonitrile is used as a pore-foaming agent, and prepolymerization is carried out for 16h at the temperature of 8 ℃.
(4) Polymerization reaction: slowly adding an initiator Azobisisobutyronitrile (AIBN), a crosslinking agent trimethylolpropane Trimethacrylate (TRIM) and double-bond functionalized porous silica gel microspheres into a prepolymerization system, reacting for 12h under the condition of 60 ℃, and then continuously heating to 70 ℃ and continuously reacting for 12 h;
(5) elution of template molecules: eluting the solvent with acetonitrile-acetic acid mixed solution at a ratio of 6:1, washing the material for 10 times, washing the material with absolute ethanol for 2 times, and drying at 70 ℃ for 15h for later use.
Example 4
A method for preparing silica gel matrix chromatographic packing for separating strong polar drugs comprises the following steps:
(1) silica gel selection and activation treatment: porous silica gel microspheres (purchased from Fuji of Japan) with the particle size of 5 microns and the pore diameter of 30nm are selected as carriers, are soaked for 3 hours by using dilute nitric acid with the mass fraction of 15 percent, are washed by deionized water until the supernatant is neutral, are washed by absolute ethyl alcohol for 1 time, and are dried in vacuum for 5 hours at the temperature of 100 ℃.
(2) Silica gel surface modification double bond: adding a silanization reagent gamma-methacryloxypropyltrimethoxysilane (gamma-MPS) into anhydrous toluene serving as a reaction medium, heating and refluxing for 8 hours, washing for 5 times by using the anhydrous toluene and washing for 5 times by using anhydrous ethanol to obtain double-bond modified porous silica gel microspheres, and heating for 7 hours at 70 ℃ for drying.
(3) Constructing a prepolymerization system: zidovudine and adenosine are selected as double-template molecules, acrylamide is used as a functional monomer, acetonitrile is used as a pore-foaming agent, and prepolymerization is carried out for 16h at the temperature of-5 ℃.
(4) Polymerization reaction: slowly adding an initiator Azobisisobutyronitrile (AIBN), a crosslinking agent trimethylolpropane Trimethacrylate (TRIM) and double-bond functionalized porous silica gel microspheres into a prepolymerization system, reacting for 12h under the condition of 30 ℃, and then continuously heating to 65 ℃ and continuously reacting for 12 h;
(5) elution of template molecules: eluting the solvent with acetonitrile-acetic acid mixed solution at a ratio of 6:1, washing the material for 10 times, washing the material with absolute ethanol for 2 times, and drying at 70 ℃ for 15h for later use.
The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.

Claims (9)

1. A preparation method of silica gel matrix chromatographic packing for separating strong polar drugs is characterized by comprising the following steps:
1) silica gel selection and activation treatment: selecting porous silica gel microspheres with the particle size of 2-5 microns and the pore diameter of 15-30 nm as a carrier, soaking the porous silica gel microspheres by using dilute nitric acid with the mass fraction of 8-20%, washing the porous silica gel microspheres by using deionized water until the supernatant is neutral, washing the porous silica gel microspheres for 1-3 times by using absolute ethyl alcohol, and drying the porous silica gel microspheres;
2) silica gel surface modification double bond: adding an ethylene-based or propenyl silanization reagent into anhydrous toluene serving as a reaction medium, heating and refluxing for 8-24 h, washing with the anhydrous toluene and ethanol or methanol in sequence to obtain double-bond modified porous silica gel microspheres, and drying;
3) constructing a prepolymerization system: selecting one or more than two nucleoside drugs as template molecules, methacrylic acid or acrylamide as a functional monomer, and methanol, ethanol or acetonitrile as a pore-forming agent, and carrying out prepolymerization for 5-20 h at-5-10 ℃ to obtain a prepolymerization system;
4) polymerization reaction: slowly adding an initiator, a cross-linking agent and double-bond modified porous silica gel microspheres into a prepolymerization system, and reacting for 12-48 h at 30-70 ℃;
5) elution of template molecules: eluting the chromatographic separation material for 6-18 times by using an elution solvent, and drying for later use.
2. The preparation method of the silica gel matrix chromatographic packing for separating the strong polar drugs according to claim 1, wherein in the step 1), the drying is performed by using a vacuum oven, and the temperature of the vacuum oven is set to be 50-100 ℃ for 5-16 h.
3. The method for preparing silica gel matrix chromatographic packing for separating strong polar drugs in claim 1, wherein in the step 2), the toluene is used for washing 2-5 times, and the methanol or ethanol is used for washing 2-5 times.
4. The method for preparing the silica gel matrix chromatographic packing for separating the strong polar drugs according to claim 1, wherein in the step 2), heating and drying are adopted, wherein the heating and drying temperature is 50-80 ℃, and the time is 6-16 h.
5. The method for preparing silica gel matrix chromatographic packing for strong polar drug separation according to claim 1, wherein in the step 4), the initiator is azobisisobutyronitrile; the cross-linking agent is one or more of trimethylolpropane trimethacrylate, ethylene glycol dimethacrylate or diethylbenzene.
6. The method for preparing the silica gel matrix chromatographic packing for separating the strong polar drugs according to claim 1, wherein the drying temperature in the step (5) is 50-70 ℃ and the drying time is 8-24 h.
7. The method for preparing the silica gel matrix chromatographic packing for the separation of the strong polar drugs according to any one of claims 1 to 6, wherein the nucleoside drugs are any one or a combination of zidovudine, lamivudine or adenosine.
8. The method for preparing silica gel matrix chromatographic packing for separating strong polar drugs according to claim 1, wherein the elution solvent in the step 5) is any one or two or more of methanol, acetonitrile, acetic acid, formic acid or water.
9. The method for preparing the silica gel matrix chromatographic packing for separating the strong polar drugs according to claim 1, wherein in the step 1), the porous silica gel microspheres are soaked in dilute nitric acid with a mass fraction of 8-20% for 1-5 h.
CN202110570901.4A 2021-05-25 2021-05-25 Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs Pending CN113274993A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110570901.4A CN113274993A (en) 2021-05-25 2021-05-25 Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110570901.4A CN113274993A (en) 2021-05-25 2021-05-25 Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs

Publications (1)

Publication Number Publication Date
CN113274993A true CN113274993A (en) 2021-08-20

Family

ID=77281629

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110570901.4A Pending CN113274993A (en) 2021-05-25 2021-05-25 Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs

Country Status (1)

Country Link
CN (1) CN113274993A (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114289004A (en) * 2021-12-02 2022-04-08 烟台大学 Carbon quantum dot doped liquid chromatography packing and preparation method and application thereof
CN114797808A (en) * 2022-05-11 2022-07-29 烟台大学 Fluorine-containing liquid chromatography packing for polar drug separation and preparation method thereof
CN114832799A (en) * 2022-06-01 2022-08-02 中国科学院兰州化学物理研究所 Preparation and application of carbon-point bonded silica gel chromatographic stationary phase based on eutectic solvent
CN117802004A (en) * 2024-01-16 2024-04-02 天津博创合成生物科技有限公司 Preparation method of high-purity adenine nucleoside

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6881804B1 (en) * 1999-11-02 2005-04-19 Mip Technologies Ab Porous, molecularly imprinted polymer and a process for the preparation thereof
CN111036181A (en) * 2019-12-26 2020-04-21 南京师范大学 Molecularly imprinted silica gel polymer and preparation method and application thereof
CN111495345A (en) * 2020-04-24 2020-08-07 宁波大学 Nucleoside hydrophilic interaction chromatographic stationary phase, preparation method and application
CN112341578A (en) * 2020-11-05 2021-02-09 烟台大学 Molecularly imprinted polymer coated porous silica gel chromatographic packing and preparation method thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6881804B1 (en) * 1999-11-02 2005-04-19 Mip Technologies Ab Porous, molecularly imprinted polymer and a process for the preparation thereof
CN111036181A (en) * 2019-12-26 2020-04-21 南京师范大学 Molecularly imprinted silica gel polymer and preparation method and application thereof
CN111495345A (en) * 2020-04-24 2020-08-07 宁波大学 Nucleoside hydrophilic interaction chromatographic stationary phase, preparation method and application
CN112341578A (en) * 2020-11-05 2021-02-09 烟台大学 Molecularly imprinted polymer coated porous silica gel chromatographic packing and preparation method thereof

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114289004A (en) * 2021-12-02 2022-04-08 烟台大学 Carbon quantum dot doped liquid chromatography packing and preparation method and application thereof
CN114289004B (en) * 2021-12-02 2023-12-26 烟台大学 Carbon quantum dot doped liquid chromatographic packing and preparation method and application thereof
CN114797808A (en) * 2022-05-11 2022-07-29 烟台大学 Fluorine-containing liquid chromatography packing for polar drug separation and preparation method thereof
CN114797808B (en) * 2022-05-11 2024-03-22 烟台大学 Fluorine-containing liquid chromatography packing for polar medicine separation and preparation method thereof
CN114832799A (en) * 2022-06-01 2022-08-02 中国科学院兰州化学物理研究所 Preparation and application of carbon-point bonded silica gel chromatographic stationary phase based on eutectic solvent
CN114832799B (en) * 2022-06-01 2023-02-28 中国科学院兰州化学物理研究所 Preparation and application of carbon-point bonded silica gel chromatographic stationary phase based on eutectic solvent
CN117802004A (en) * 2024-01-16 2024-04-02 天津博创合成生物科技有限公司 Preparation method of high-purity adenine nucleoside
CN117802004B (en) * 2024-01-16 2024-06-14 天津博创合成生物科技有限公司 Preparation method of high-purity adenine nucleoside

Similar Documents

Publication Publication Date Title
CN113274993A (en) Preparation method of silica gel matrix chromatographic packing for separating strong-polarity drugs
DE60035603T2 (en) NEW MOLECULAR EMBOSSED POLYMERS PUT ON A SOLID CARRIER
CN103958051B (en) For the adsorbent on organic molecule purification, surface with cross-linked polyvinylamine
CN101246178A (en) System for adsorbing, separating and detecting ultra-drop target protein
CN112341578A (en) Molecularly imprinted polymer coated porous silica gel chromatographic packing and preparation method thereof
Azodi-Deilami et al. The syntheses and characterization of molecularly imprinted polymers for the controlled release of bromhexine
CN103974766A (en) Sorbent comprising on its surface a cationic or protonizable aliphatic residue for the purification of organic molecules
Liu et al. Fabrication of monodisperse poly (allyl glycidyl ether-co-divinyl benzene) microspheres and their application in anion-exchange stationary phase
CN110361462B (en) Molecular engram tube tip micro-extraction head and preparation method thereof
CN108864364B (en) Preparation method of L-phenylalanine molecularly imprinted polymer
CN114950384B (en) Graphene oxide/poly eutectic solvent molecularly imprinted composite material, and preparation method and application thereof
CN101464439B (en) Production method for protein molecule imprinting integral column
CN108976361B (en) Preparation method and application of single-hole hollow boron affinity imprinted polymer
CN111574666B (en) Compound extraction plate and preparation method and application thereof
JPH0285758A (en) Ion exchanging composite composition for ion chromatography
CN115926046B (en) Catalpol magnetic surface molecularly imprinted polymer and preparation method and application thereof
CN108659159B (en) Molecularly imprinted microsphere for detecting teicoplanin and preparation and application thereof
CN115121234B (en) Ion liquid embedded alkyl ester mixed mode chromatographic stationary phase and preparation method and application thereof
CN102382273A (en) Preparation method of 17 beta-estradiol molecular-imprinted composite microspheres
CN103974764A (en) Sorbent comprising on its surface an aromatic ring system having an anionic or deprotonizable group for the purification of organic molecules
CN212134597U (en) Molecular imprinting plate
CN109721759B (en) Acetyl glucosamine imprinted material and application thereof in recognition of acetyl glucosamine and acetyl glucosamine modified peptide fragment
CN110818836A (en) Vitamin E molecularly imprinted polymer, two-step swelling preparation method and application thereof
CN107552022B (en) Star-shaped magnetic response organic adsorption material and preparation method thereof
JP3972662B2 (en) Cation exchanger, method for producing the same, and use thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20210820