CN111632582A - Silica gel reverse phase chromatographic packing and preparation method and application thereof - Google Patents

Silica gel reverse phase chromatographic packing and preparation method and application thereof Download PDF

Info

Publication number
CN111632582A
CN111632582A CN201910155766.XA CN201910155766A CN111632582A CN 111632582 A CN111632582 A CN 111632582A CN 201910155766 A CN201910155766 A CN 201910155766A CN 111632582 A CN111632582 A CN 111632582A
Authority
CN
China
Prior art keywords
silica gel
reverse phase
acid
octadecylsilane
sugammadex sodium
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.)
Granted
Application number
CN201910155766.XA
Other languages
Chinese (zh)
Other versions
CN111632582B (en
Inventor
陈再洁
屠炳芳
任兴发
郭德勇
马建辉
李崟
薛昆鹏
吴小梅
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.)
Shanghai Wellrich Testing Technology Co ltd
Welch Materials (shanghai) Inc
Original Assignee
Welch Materials (shanghai) Inc
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 Welch Materials (shanghai) Inc filed Critical Welch Materials (shanghai) Inc
Priority to CN201910155766.XA priority Critical patent/CN111632582B/en
Publication of CN111632582A publication Critical patent/CN111632582A/en
Application granted granted Critical
Publication of CN111632582B publication Critical patent/CN111632582B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. 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
    • B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
    • B01J20/103—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate comprising 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
    • B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/223—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material containing metals, e.g. organo-metallic compounds, coordination complexes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • 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
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
    • B01J2220/48—Sorbents characterised by the starting material used for their preparation
    • B01J2220/4806—Sorbents characterised by the starting material used for their preparation the starting material being of inorganic character
    • 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
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
    • B01J2220/48—Sorbents characterised by the starting material used for their preparation
    • B01J2220/4812—Sorbents characterised by the starting material used for their preparation the starting material being of organic character
    • 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
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
    • B01J2220/52—Sorbents specially adapted for preparative chromatography

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Materials Engineering (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Sustainable Development (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

The invention provides a silica gel reverse phase chromatographic packing and a preparation method and application thereof. The silica gel reversed phase chromatographic packing has simple preparation method, can be used for purifying sugammadex sodium, ensures that the purity of the sugammadex sodium in a sample eluent is more than 99.2 percent so as to meet the requirement of industrial production and completely meet the quality standard of raw material medicines.

Description

Silica gel reverse phase chromatographic packing and preparation method and application thereof
Technical Field
The invention relates to a medical synthesis technology, in particular to a silica gel reversed phase chromatographic packing and a preparation method and application thereof.
Background
Sugammadex sodium is a derivative of gamma-cyclodextrin, the molecule of which consists of a lipophilic core and a hydrophilic outer end, and is a selective muscle relaxant antagonist with the chemical name: 6-Perdeoxy-6-per (2-carboxyethyl) thio-gamma-cyclodextrin sodium salt (octasodium salt) having the following structural formula:
Figure BDA0001982847840000011
the sugammadex sodium is used for reversing the action of a neuromuscular blocking drug rocuronium bromide or vecuronium bromide which is conventionally used, and can immediately reverse the action of rocuronium bromide which is conventionally used by adults and the action of rocuronium bromide which is conventionally used by children and teenagers (2-17 years old). In recent years, with the development of preparation or purification technology, various sugammadex sodium purification processes have been reported, but sugammadex sodium has a complex structure and contains a plurality of chiral centers, and particularly, many gamma-cyclodextrin structural analogs exist, and the methods reported in the existing documents cannot provide high-purity sugammadex sodium and meet the requirements of industrial mass production.
Therefore, it is desirable to provide a new method for purifying sugammadex sodium to solve the above problems.
It is noted that the information disclosed in the foregoing background section is only for enhancement of background understanding of the invention and therefore it may contain information that does not constitute prior art that is already known to a person of ordinary skill in the art.
Disclosure of Invention
The invention aims to overcome at least one defect of the prior art and provides a silica gel reversed phase chromatographic packing and a preparation method thereof, wherein the silica gel reversed phase chromatographic packing can be used for purifying sugammadex sodium, so that the purity of the sugammadex sodium in a sample eluent is more than 99 percent, the industrial production requirement is met, and the quality standard of a bulk drug is completely met.
In order to achieve the purpose, the invention adopts the following technical scheme:
one aspect of the invention provides a silica gel reverse phase chromatography packing comprising: silica gel and organosilane bonded on the surface of the silica gel, wherein the organosilane comprises octadecylsilane and other silanes, and the general chemical structure of the octadecylsilane is as follows:
Figure BDA0001982847840000021
wherein R is1、R2Each independently selected from hydrogen or C1-4Alkyl of (A), X1As reactive groups, preference is given to chlorine, methoxy or ethoxy.
According to one embodiment of the invention, the chemical structure of the other silanes is of the general formula:
Figure BDA0001982847840000022
wherein R is3、R4Is C1-4Alkyl of (A), X2Is a reactive group, preferably chloro, methoxy or ethoxy; m and n are integers of 1-3, and m + n is less than or equal to 4.
According to one embodiment of the invention, the other silane is selected from one or more of methyltrimethoxysilane, trimethylchlorosilane, monomethyltrichlorosilane and dimethyldichlorosilane.
According to one embodiment of the invention, wherein the octadecylsilane is selected from the group consisting of octadecyldimethylchlorosilane, octadecylmonomethylchlorosilane, octadecyldimethylmethoxysilane, octadecyldimethylethoxysilane, octadecylmethylmethylmethoxysilane and octadecylmonomethylethoxysilane.
Another aspect of the present invention provides a method for preparing the silica gel reverse phase chromatography packing, comprising the steps of:
activating and pretreating silica gel to obtain activated silica gel with silicon hydroxyl on the surface;
mixing octadecylsilane and other silanes into a premix;
and mixing the premix and the activated silica gel in an organic solvent, and carrying out reflux reaction to obtain the silica gel reverse phase chromatographic packing.
According to one embodiment of the invention, the mass ratio of the octadecylsilane and the other silane is 1 (0.2-1.3); the mass ratio of the silica gel to the premix is 1 (0.2-1.3).
According to an embodiment of the present invention, the reflux reaction is performed under an inert atmosphere, and the time of the reflux reaction is 12 to 48 hours.
In another aspect of the present invention, a method for purifying sugammadex sodium is provided, wherein the method for purifying sugammadex sodium by using the silica gel reverse phase chromatography packing comprises the following steps:
loading the crude sugammadex sodium product on a chromatographic column of a silica gel reversed phase chromatographic packing, and collecting a sample eluent after elution, wherein the purity of the sugammadex sodium in the sample eluent is more than 99%.
According to an embodiment of the present invention, wherein the purity of the crude sugammadex sodium is 80%, the single impurity content in the sample eluent is less than 0.05%.
According to one embodiment of the invention, the chromatographic column is eluted by acetonitrile/water solution, wherein the acetonitrile content is 5-40% by volume, preferably 10-30% by volume and more preferably 19% by volume; the acetonitrile/water solution also contains acid, and the acid is selected from one or more of formic acid, perchloric acid, acetic acid, trifluoroacetic acid and phosphoric acid; the concentration of the acid is 0.05 wt% to 1.0 wt%, preferably 0.2 wt%.
According to the technical scheme, the invention has the beneficial effects that:
the invention provides a novel silica gel reversed phase chromatographic packing and a preparation method thereof, and the preparation method of the silica gel chromatographic packing has the advantages of simplicity, good stability, good reproducibility, easiness in large-scale production and the like. The silica gel reverse phase chromatographic packing is adopted for purifying the sugammadex sodium, the purity of the sugammadex sodium in a sample eluent can reach 99.2 percent, the single impurity content is less than 0.05 percent, the yield is high, and the production standard of raw material medicines is met.
Drawings
FIG. 1 is a liquid chromatogram of purified sugammadex sodium of example 1.
Detailed Description
The following presents various embodiments or examples in order to enable those skilled in the art to practice the invention with reference to the description herein. These are, of course, merely examples and are not intended to limit the invention. The endpoints of the ranges and any values disclosed in the present application are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to yield one or more new ranges of values, which ranges of values should be considered as specifically disclosed herein.
One aspect of the invention provides a silica gel reverse phase chromatography packing comprising: silica gel and organosilane bonded on the surface of the silica gel, wherein the organosilane comprises octadecylsilane and other silanes, and the general chemical structure of the octadecylsilane is as follows:
Figure BDA0001982847840000041
wherein R is1、R2Independently selected from hydrogen or C1-4Alkyl of (A), X1As reactive groups, preference is given to chlorine, methoxy or ethoxy.
The "other silane" refers to other kinds of organosilanes other than octadecylsilane. According to the invention, octadecylsilane and other silanes are selected as bonding reaction reagents, octadecylsilane is taken as a main functional group, so that a good nonpolar acting force is obtained, intermolecular action can be carried out on the octadecylsilane and a target substance, and a substance is properly retained, and the action of other silanes provides multiple selectivity and retention mechanisms, so that the target substance and other unnecessary substances can be well separated, the stability of the bonding phase in a mobile phase is increased, the service life of the filler is prolonged to a great extent, and the production cost is reduced.
In some embodiments, the other silane coupling agent has the general chemical formula:
Figure BDA0001982847840000042
wherein R is3、R4Is C1-4Alkyl of (A), X2Is a reactive group, preferably chloro, methoxy or ethoxy; m and n are integers of 1-3, and m + n is less than or equal to 4.
Further, the other silanes include, but are not limited to, one or more of methyltrimethoxysilane, trimethylchlorosilane, monomethyltrichlorosilane, or dimethyldichlorosilane.
In some embodiments, wherein the octadecylsilane is selected from the group consisting of octadecyldimethylchlorosilane, octadecylmonomethylchlorosilane, octadecyldimethylmethoxysilane, octadecyldimethylethoxysilane, octadecylmethylmethylmethoxysilane, and octadecylmonomethylethoxysilane.
Another aspect of the present invention provides a method for preparing the silica gel reverse phase chromatography packing, comprising the steps of:
the silica gel is activated and pretreated to obtain activated silica gel with silicon hydroxyl on the surface, specifically, for example, the silica gel, pyridine and imidazole are placed in an organic solvent to be mixed and stirred for reaction, heated and stirred for refluxing for a certain time, and preferably, water evaporated after the reaction is separated by a water separator to obtain a solution containing the activated silica gel. Mixing octadecylsilane and other silanes to obtain a premix, adding the premix into a solution containing activated silica gel to perform reflux reaction, and treating to obtain the bonded silica gel reversed-phase chromatographic packing.
Preferably, the silica gel reverse phase chromatographic packing has a particle size of 5-60 μm and a specific surface area of 100-300 m2/g。
In some embodiments, the organic solvent is preferably a non-polar solvent, such as toluene, xylene, n-hexane, or n-heptane. Toluene is preferred. The silica gel is catalyzed to become active by firstly reacting the silica gel with pyridine and imidazole for a certain time, preferably 12-24 hours, at 50-120 ℃, so that a chemical functional group can be bonded.
In some embodiments, the mass ratio of octadecylsilane to other silanes is 1 (0.2-1.3), preferably 1 (0.5-1.1); the mass ratio of the silica gel to the premix is 1 (0.2-1.3), preferably 1 (0.5-1.1).
In some embodiments, the reflux reaction is performed under an inert atmosphere, such as nitrogen (N)2) (ii) a The time of the reflux reaction is 12 to 24 hours, preferably 18 hours.
In another aspect of the present invention, a method for purifying sugammadex sodium is provided, wherein the method for purifying silica gel reverse phase chromatography packing prepared by the method comprises the following steps:
loading the crude sugammadex sodium product on a chromatographic column of a silica gel reversed phase chromatographic packing, and collecting a sample eluent after elution, wherein the purity of the sugammadex sodium in the sample eluent is more than 99.2%.
In some embodiments, the crude sugammadex sodium has a purity of 80%, and the single impurity content of the resulting sample eluate after elution with the silica gel chromatography packing of the present invention may be less than 0.05%.
In some embodiments, the chromatography column is eluted with acetonitrile/water solution, wherein the acetonitrile content is 5-40% by volume, preferably 10-30% by volume, and more preferably 19% by volume; i.e. the acetonitrile content refers to the volume percentage of acetonitrile in the solution. Specifically, water and acetonitrile may be pumped separately through the A, B line to the silica gel reverse phase chromatography column for elution.
In order to reduce the adsorption of sugammadex on the silica gel reverse phase and ensure the purification effect and yield, in some embodiments, the acetonitrile/water solution also contains an acid, and the acid is selected from one or more of formic acid, perchloric acid, acetic acid, trifluoroacetic acid and phosphoric acid; the concentration of the acid is 0.05 wt% to 1.0 wt%, preferably 0.2 wt%.
In some embodiments, the flow rate of the eluent in the purification process is 1-2L/min, and can be adjusted according to the actual inner diameter of the column.
The invention is further described below by means of specific examples, without restricting the scope of the invention in any way.
It should be noted that the "purity" or "content" of the samples described in the following examples was obtained by HPLC assay; the detection conditions are as follows: the column was a Boltimate C18(2.7um, 4.6 x 150 mm); the mobile phase is phosphoric acid water and acetonitrile, the speed is 0.8ml/min, and the detection wavelength is 210 nm.
Preparation example 1
10.0g of silica gel, 3.0g (0.044mol) of pyridine imidazole and 90mL of toluene are accurately weighed and placed in a 100mL three-neck flask, the mixture is stirred and refluxed for 2 hours at 120 ℃, and the distilled water is separated out by a water separator. Then cooled to room temperature under N2Adding 8.0g of premixed octadecyldimethylchlorosilane and methyltrimethoxysilane under protection, wherein the mass ratio of the octadecyldimethylchlorosilane to the methyltrimethoxysilane is 4:1, reacting for 18h under the reflux condition, and then carrying out treatment reaction to obtain a bonded stationary phase, namely the silica gel reversed phase chromatographic packing.
Example 1
Filling a preparation column: wetting 11kg of silica gel reversed phase chromatography filler (10 μm particle size, 300mm DAC column) obtained in preparation example 1 with 28L of isopropanol, homogenizing with a homogenizing device, loading the homogenate into a DAC column tube, performing dynamic axial compression to enable the loading pressure to reach 80-100 Bar, and flushing the preparation column for later use by using methanol of which the CV (column volume) is 5-10 times as much as that of the mobile phase.
300g of crude sugammadex (purity 82%) was dissolved in 1000ml of 0.1% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.2% aqueous formic acid and acetonitrile were pumped separately to a DAC column using A, B tubing for elution, maintaining the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 255g of sugammadex sodium, the yield is 85%, the purity is 99.87%, and the single impurity content is less than 0.05%. Fig. 1 shows a liquid chromatogram of purified sugammadex sodium of example 1.
Example 2:
the preparative column packed according to example 1 was ready for use.
300g of crude sugammadex sodium (purity 83.1%) are dissolved in 1000ml of 0.15% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.15% aqueous formic acid and acetonitrile were pumped separately to a DAC column using A, B tubing for elution, maintaining the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 255g of sugammadex sodium, the yield is 85%, the purity is 99.96%, and the single impurity content is less than 0.05%.
Example 3:
preparative columns packed according to example 1 for use
300g of crude sugammadex sodium (purity 85.5%) are dissolved in 1000ml of 0.1% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.2% aqueous formic acid and acetonitrile were pumped separately to a DAC column using A, B tubing for elution, maintaining the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 249g of sugammadex sodium, the yield is 83%, the purity is 99.83%, and the single impurity content is less than 0.05%.
Example 4:
the preparative column packed according to example 1 was ready for use.
300g of crude sugammadex sodium (purity 90.3%) are dissolved in 1000ml of 0.1% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.2% aqueous formic acid and acetonitrile were pumped separately to a DAC column using A, B tubing for elution, maintaining the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 260g of sugammadex sodium, the yield is 87%, the purity is 99.83%, and the single impurity content is less than 0.05%.
Therefore, the silica gel reversed phase chromatographic packing has good purification effect on the sugammadex sodium, the purity can basically reach more than 99.2%, and the single impurities are less than 0.05%, so that the quality standard of the sugammadex sodium as a raw material medicine is completely met.
It should be noted by those skilled in the art that the described embodiments of the present invention are merely exemplary and that various other substitutions, alterations, and modifications may be made within the scope of the present invention. Accordingly, the present invention is not limited to the above-described embodiments, but is only limited by the claims.

Claims (10)

1. A silica gel reverse phase chromatography packing comprising: silica gel and organosilane bonded on the surface of the silica gel, wherein the organosilane comprises octadecylsilane and other silanes, and the general chemical structure of the octadecylsilane is as follows:
Figure FDA0001982847830000011
wherein R is1、R2Each independently selected from hydrogen or C1-4Alkyl of (A), X1As reactive groups, preference is given to chlorine, methoxy or ethoxy.
2. The silica gel reverse phase chromatography packing of claim 1, wherein the other silane has the general chemical structure:
Figure FDA0001982847830000012
wherein R is3、R4Is C1-4Alkyl of (A), X2Is a reactive group, preferably chloro, methoxy or ethoxy; m and n are integers of 1-3, and m + n is less than or equal to 4.
3. The silica gel reverse phase chromatography packing material of claim 2, wherein the other silane is selected from one or more of methyltrimethoxysilane, trimethylchlorosilane, monomethyltrichlorosilane, and dimethyldichlorosilane.
4. A silica gel reverse phase chromatography packing material according to any one of claims 1 to 3, wherein the octadecylsilane is selected from one or more of octadecyldimethylchlorosilane, octadecylmonomethylchlorosilane, octadecyldimethylmethoxysilane, octadecyldimethylethoxysilane, octadecylmethylmethylmethoxysilane and octadecylmonomethylethoxysilane.
5. A method of preparing the silica gel reverse phase chromatography packing of any one of claims 1 to 4, comprising the steps of:
activating and pretreating silica gel to obtain activated silica gel with silicon hydroxyl on the surface;
mixing octadecylsilane and other silanes into a premix;
and mixing the premix and the activated silica gel in an organic solvent, and carrying out reflux reaction to obtain the silica gel reverse phase chromatographic packing.
6. The method according to claim 5, wherein the mass ratio of the octadecylsilane to the other silane is 1 (0.2-1.3); the mass ratio of the silica gel to the premix is 1 (0.2-1.3).
7. The method according to claim 5, wherein the reflux reaction is carried out under an inert atmosphere, and the time of the reflux reaction is 12-48 hours.
8. A purification method of sugammadex sodium, which adopts the silica gel reverse phase chromatography packing material of any one of claims 1 to 4 for purification, and comprises the following steps:
and loading the crude sugammadex sodium on a chromatographic column of the silica gel reverse phase chromatographic packing, and collecting a sample eluent after elution, wherein the purity of the sugammadex sodium in the sample eluent is more than 99.2%.
9. A purification process according to claim 8, wherein the purity of the crude sugammadex sodium is 80% and the single impurity content in the sample eluate is less than 0.05%.
10. The purification process according to claim 8, wherein the chromatography column is eluted with acetonitrile/water solution, the acetonitrile content being 5-40%, preferably 10-30%, more preferably 19% by volume; the acetonitrile/water solution also contains acid, and the acid is selected from one or more of formic acid, perchloric acid, acetic acid, trifluoroacetic acid and phosphoric acid; the concentration of the acid is 0.05 wt% to 1.0 wt%, preferably 0.2 wt%.
CN201910155766.XA 2019-03-01 2019-03-01 Silica gel reverse phase chromatographic packing and preparation method and application thereof Active CN111632582B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910155766.XA CN111632582B (en) 2019-03-01 2019-03-01 Silica gel reverse phase chromatographic packing and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910155766.XA CN111632582B (en) 2019-03-01 2019-03-01 Silica gel reverse phase chromatographic packing and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN111632582A true CN111632582A (en) 2020-09-08
CN111632582B CN111632582B (en) 2023-02-28

Family

ID=72322747

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910155766.XA Active CN111632582B (en) 2019-03-01 2019-03-01 Silica gel reverse phase chromatographic packing and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN111632582B (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5993653A (en) * 1997-08-11 1999-11-30 Phenomenex Composition and column used in HPLC
CN101234337A (en) * 2007-11-14 2008-08-06 天津大学 Silica matrix chromatogram packing
CN103357390A (en) * 2012-11-12 2013-10-23 北京迪马欧泰科技发展中心 Multi-layer structure bonded silica gel liquid chromatography packing and synthesis method thereof
CN108176387A (en) * 2018-03-08 2018-06-19 浙江月旭材料科技有限公司 A kind of silica gel chromatographic column filling material, preparation method and applications
CN108456264A (en) * 2017-02-22 2018-08-28 江苏恒瑞医药股份有限公司 A kind of purification process for the more glucose sodium that relaxes

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5993653A (en) * 1997-08-11 1999-11-30 Phenomenex Composition and column used in HPLC
US5993653C1 (en) * 1997-08-11 2001-11-06 Phenomenex Composition and column used in hplc
CN101234337A (en) * 2007-11-14 2008-08-06 天津大学 Silica matrix chromatogram packing
CN103357390A (en) * 2012-11-12 2013-10-23 北京迪马欧泰科技发展中心 Multi-layer structure bonded silica gel liquid chromatography packing and synthesis method thereof
CN108456264A (en) * 2017-02-22 2018-08-28 江苏恒瑞医药股份有限公司 A kind of purification process for the more glucose sodium that relaxes
CN108176387A (en) * 2018-03-08 2018-06-19 浙江月旭材料科技有限公司 A kind of silica gel chromatographic column filling material, preparation method and applications

Also Published As

Publication number Publication date
CN111632582B (en) 2023-02-28

Similar Documents

Publication Publication Date Title
O'Gara et al. Simple preparation of a C8 HPLC stationary phase with an internal polar functional group
Gao et al. Preparation and recognition performance of cytisine alkaloid‐imprinted material prepared using novel surface molecular imprinting technique
EP0128886B1 (en) Separation material, methods of producing a separation material and use of orosomucoid, functional analogs thereto or derivatives or fragments thereof for separation purposes
GB2074892A (en) Mixed phase chromatographic compositions
WO1995000463A1 (en) Optical isomer separating agent and process for producing the same
CN109174048B (en) Silica gel chromatographic packing and preparation method thereof
EP2755755A1 (en) Sorbent comprising on its surface a cationic or protonizable aliphatic residue for the purification of organic molecules
EP2028487B1 (en) Filler for optical isomer separation
EP2031388A1 (en) Filler for optical isomer separation
CN111632582B (en) Silica gel reverse phase chromatographic packing and preparation method and application thereof
CN106866900B (en) A kind of photoresponse molecularly imprinted material on surface and its preparation method and application
WO1995031420A1 (en) Separating agent for optical isomers
US4683341A (en) Optical resolution of oxycyclopentenone
Sutthivaiyakit et al. Immobilization of 5-methylene-2-(2′-thiazolylazo)-anisole on silica and its application in preconcentration of palladium
CN111153909B (en) A double-template molecular imprinting purification method for alpha-and beta-carotene in Stephania tetrandra
JPH06211902A (en) Substituted aromatic carbamate derivative of polysaccharide, and separating agent
JP2669554B2 (en) Novel polysaccharide derivatives and separating agents
CN111729661A (en) Chromatography media for separating boron-containing species
CN1943848A (en) Hydrophilic forward chromatographic column, filler and separating method
CN117138762A (en) Low-loss mixed separation mode liquid chromatographic packing and preparation method and application thereof
JP3634929B2 (en) Method for producing packing material for high performance liquid chromatography
Cheong et al. Allyltrimethoxysilane as the reagent of double bond introduction to porous silica for preparation of a chiral stationary phase in comparison with allyltriethoxysilane
CN113797905B (en) Pyridine dicarboxamide bridged bis-beta-cyclodextrin stationary phase and preparation method and application thereof
CN1472003A (en) Aromatic hydrocarbon linked silica gel solid phase and its preparation and use
JP3029302B2 (en) Packing material for chromatography and method for producing the same

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
TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20210126

Address after: 203201 1001b, area a, building 1, 3000 Longdong Avenue, Pudong New Area pilot Free Trade Zone, Shanghai

Applicant after: WELCH MATERIALS (SHANGHAI) Inc.

Applicant after: Shanghai wellrich Testing Technology Co.,Ltd.

Address before: 203201 1001b, area a, building 1, 3000 Longdong Avenue, Pudong New Area pilot Free Trade Zone, Shanghai

Applicant before: WELCH MATERIALS (SHANGHAI) Inc.

CB02 Change of applicant information
CB02 Change of applicant information

Address after: 201613 Room 102, 2 / F and 3 / F, 1 / F, building 10, 85 Mingnan Road, Songjiang District, Shanghai

Applicant after: WELCH MATERIALS (SHANGHAI) Inc.

Applicant after: Shanghai wellrich Testing Technology Co.,Ltd.

Address before: 203201 1001b, area a, building 1, 3000 Longdong Avenue, Pudong New Area pilot Free Trade Zone, Shanghai

Applicant before: WELCH MATERIALS (SHANGHAI) Inc.

Applicant before: Shanghai wellrich Testing Technology Co.,Ltd.

GR01 Patent grant
GR01 Patent grant