CN112480028A - Method for chiral resolution of promethazine - Google Patents
Method for chiral resolution of promethazine Download PDFInfo
- Publication number
- CN112480028A CN112480028A CN202011387808.1A CN202011387808A CN112480028A CN 112480028 A CN112480028 A CN 112480028A CN 202011387808 A CN202011387808 A CN 202011387808A CN 112480028 A CN112480028 A CN 112480028A
- Authority
- CN
- China
- Prior art keywords
- promethazine
- chiral resolution
- mobile phase
- chiral
- column
- 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
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
- C07D279/26—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom without other substituents attached to the ring system
-
- 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
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3833—Chiral chromatography
-
- 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
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/40—Selective adsorption, e.g. chromatography characterised by the separation mechanism using supercritical fluid as mobile phase or eluent
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention provides a method for chiral resolution of promethazine, which comprises the following steps: (1) preparing a test solution: weighing a certain amount of promethazine reference substance, and dissolving the promethazine reference substance by adopting an organic solution to prepare a promethazine test sample solution; and (2) chiral resolution using supercritical chromatography: separating promethazine enantiomer in the promethazine test sample solution by supercritical chromatography, wherein the stationary phase is polysaccharide derivative chiral chromatographic column, the mobile phase A is supercritical fluid, the mobile phase B is organic solvent, the column temperature is 30-45 deg.C, the column pressure is 10-20MPa, the column pressure is constant pressure, the flow rate is 1-3ml/min, and the ultraviolet wavelength is 254 nm. The method overcomes the defects of the prior art, and has the characteristics of mild and simple operation conditions, low cost, high sensitivity, high separation speed, environmental protection and the like.
Description
Technical Field
The invention relates to a method for chiral resolution of promethazine.
Background
Promethazine is an inorganic substance, also called finasteride, with the chemical formula C17H20N2S, structural formula shown below, is a common antitussive drug, an antihistamine, which competitively blocks histamine H1 receptor, antagonizes histamine-induced telangiectasia, and decreases its permeability. Therefore, the cough caused by the stimulation of the trachea can be smoothed. Because promethazine has a chiral center, it has a dextrorotatory form with a spatial configuration of R-and a levorotatory form with a spatial configuration of S-. At present, no literature report is found about the drug effect and toxicological research of different enantiomers of promethazine R, S configuration, so a chiral resolution method of promethazine enantiomer is established toIt is important to further study.
The chiral resolution of promethazine usually adopts high performance liquid chromatography and capillary electrophoresis, and the liquid chromatography mainly adopts ovomucoid chiral stationary phase or cellulose chiral stationary phase for resolution, but the requirements on mobile phase are higher (in the aspects of mobile phase reagent purity and the like), the experimental cost is higher, and the column efficiency is low. The capillary electrophoresis mainly adopts cyclodextrin substances as electrophoresis media to realize the separation and detection of promethazine enantiomers, and has the advantages of low experimental cost, wide application range, long analysis time, low separation degree and no prospect of amplification to preparation scale.
In summary, the methods for chiral separation of promethazine in the prior art have the following disadvantages: higher requirements on mobile phase, higher experimental cost, long analysis time and lower separation degree.
Disclosure of Invention
In order to overcome the technical defects of high requirement on a mobile phase, high experimental cost, long analysis time and low separation degree of the method for chiral separation of promethazine in the prior art, the invention aims to provide a method for chiral separation of promethazine, which comprises the following steps:
(1) preparing a test solution: weighing a certain amount of promethazine reference substance, and dissolving the reference substance by adopting an organic solution to prepare a promethazine test sample solution; and
(2) chiral resolution was performed using supercritical chromatography: separating promethazine enantiomer in the promethazine sample test solution by supercritical chromatography, wherein the stationary phase is polysaccharide derivative chiral chromatographic column, the mobile phase A is supercritical fluid, the mobile phase B is organic solvent, the column temperature is 30-45 deg.C, the column pressure is 10-20MPa, the column pressure is constant pressure, and the flow rate is 1-3 ml/min. SupercriticaL Fluid Chromatography (SFC) is performed using SupercriticaL fluid CO2As a mobile phase, separating and separating by virtue of the solvating power of the mobile phaseThe separation technology has the characteristics of simple and convenient operation conditions, quick separation, high sensitivity, environmental protection and the like.
Further, the organic solvent in the steps (1) and (2) is one or more selected from methanol, ethanol, acetonitrile and isopropanol. Methanol is preferred.
Further, the organic solvent in the step (2) accounts for 10 to 20% of the volume of the mobile phase A and the mobile phase B.
Further, the volume ratio of the organic solvent in the step (2) in the mobile phase a and the mobile phase B is 15%, the organic solvent comprises methanol and isopropanol, and the volume ratio is methanol: isopropanol-9: 1.
Further, the polysaccharide derivative in step (2) is amylose-tris (3, 5-dimethylphenylcarbamate).
Further, the supercritical fluid in the step (2) is supercritical carbon dioxide. Because the supercritical fluid CO2 has the characteristics of low viscosity, high diffusion rate and high mass transfer capacity, the supercritical fluid CO2 has unique advantages in the field of chiral compound and analogue separation, and has the advantages of low requirement on a mobile phase, low experimental cost, short analysis time, greenness, environmental protection and high separation degree.
Further, the flow rate in step (2) is 2 ml/min.
Further, the column pressure in step (2) is 10 MPa.
Further, the column temperature in step (2) was 35 ℃.
All reagents in this application are commercially available.
Compared with the prior art, the technical scheme of the application has the following beneficial effects:
according to the technical scheme, the promethazine is directly subjected to chiral resolution by using a supercritical fluid chromatography, and a mobile phase of the promethazine consists of supercritical carbon dioxide and an organic solvent, so that the emission of organic waste liquid can be reduced, and the method is green and environment-friendly; because the supercritical fluid CO2 has the characteristics of low viscosity, high diffusion rate and high mass transfer capacity, the method has unique advantages in the field of chiral compound and analogue separation, overcomes the defects of the prior art, and has the characteristics of mild and simple operation conditions, low cost, high sensitivity, high separation speed and the like.
Drawings
FIG. 1 is a chromatographic separation profile of example 1;
FIG. 2 is a chromatographic separation profile of example 2;
FIG. 3 is a chromatographic separation profile of example 3;
FIG. 4 is a chromatographic separation profile of example 4;
FIG. 5 is a chromatographic separation profile of example 5;
FIG. 6 is a chromatographic separation profile of example 6;
FIG. 7 is a chromatographic separation profile of example 7;
FIG. 8 is a chromatogram of the comparative example.
Detailed Description
The advantages of the invention are further illustrated in the following description of specific embodiments in conjunction with the accompanying drawings.
Reference will now be made in detail to the exemplary embodiments, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, like numbers in different drawings represent the same or similar elements unless otherwise indicated. The implementations described in the exemplary embodiments below are not intended to represent all implementations consistent with the present disclosure. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present disclosure, as detailed in the appended claims.
The terminology used in the present disclosure is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.
Example 1:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. Using supercritical fluid chromatographyThe apparatus is (SHIMADZU) Nexera UC SFC system, and uses (Daicel) CHIRALPAK AD-H chiral chromatographic column, which is a silica gel surface coated with amylose-tri (3, 5-dimethylphenylcarbamate) polysaccharide derivative type chiral chromatographic column with the specification of 250mm multiplied by 4.6mm, the particle size of 5 μm, and the mobile phase A is supercritical CO2The mobile phase B is two organic solvents of methanol-isopropanol (90: 10, v/v), and the B phase accounts for 15%. The column temperature of the polysaccharide derivative chiral chromatographic column is 35 ℃; the column pressure is 10 MPa; the detection wavelength is 254 nm; the flow rate is 2 mL/min; the injection volume was 5. mu.L.
See FIG. 1 for results. As can be seen from FIG. 1, the two enantiomeric chromatographic peaks of promethazine can be separated effectively, and simultaneously, the elution order of the enantiomers of promethazine is studied by using a chiral laser-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the corresponding relationship between the isomers, the first peak is the dextroisomer of promethazine R-, the second peak is the levoisomer of promethazine S-, and the chromatograph shows that the separation degree is 2.618.
Example 2:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. The method adopts supercritical fluid chromatography as (SHIMADZU) Nexera UC SFC system, uses (Daicel) CHIRALPAK AD-H chiral chromatographic column, is a silica gel surface coated with amylose-tri (3, 5-dimethylphenyl carbamate) polysaccharide derivative chiral chromatographic column, and has the specification of 250mm multiplied by 4.6mm, the particle size of 5 mu m, and the mobile phase A is supercritical CO2The mobile phase B is two organic solvents of methanol-isopropanol (90: 10, v/v), and the B phase accounts for 15%. The column temperature of the polysaccharide derivative chiral chromatographic column is 40 ℃; the column pressure is 10 MPa; the detection wavelength is 254 nm; the flow rate is 2 mL/min; the injection volume was 5. mu.L.
See FIG. 2 for results. As can be seen from FIG. 2, the two enantiomeric chromatographic peaks of promethazine were separated effectively, and the elution order of the enantiomers of promethazine was investigated by a chiral laser-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the correspondence between the isomers, the first peak being the dextroisomer of promethazine R-, and the second peak being the levoisomer of promethazine S-, and the chromatographic instrument showed a resolution of 2.169.
Example 3:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. A supercritical fluid chromatograph is adopted as a (SHIMADZU) Nexera UC SFC system, a (Daicel) CHIRALPAK AD-H chiral chromatographic column is used, the chiral chromatographic column is a polysaccharide derivative type chiral chromatographic column of which the silica gel surface is coated with amylose-tri (3, 5-dimethylphenyl carbamate), the specification is 250mm multiplied by 4.6mm, the particle size is 5 mu m, the mobile phase A is supercritical CO2, the mobile phase B is methanol, and the phase B accounts for 15%. The column temperature of the polysaccharide derivative chiral chromatographic column is 40 ℃; the column pressure is 10 MPa; the detection wavelength is 254 nm; the flow rate is 2 mL/min; the injection volume was 5. mu.L.
See FIG. 3 for results. As can be seen from FIG. 3, the two enantiomeric chromatographic peaks of promethazine were separated effectively, and the elution order of the enantiomers of promethazine was investigated by a chiral laser-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the correspondence between the isomers, the first peak being the dextroisomer of promethazine R-, and the second peak being the levoisomer of promethazine S-, and the chromatographic instrument showed a degree of separation of 1.163.
Example 4:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. A supercritical fluid chromatograph is adopted as a (SHIMADZU) Nexera UC SFC system, a (Daicel) CHIRALPAK AD-H chiral chromatographic column is used, the chiral chromatographic column is a silica gel surface coated with amylose-tri (3, 5-dimethylphenyl carbamate) polysaccharide derivative type chiral chromatographic column, the specification is 250mm multiplied by 4.6mm, the particle size is 5 mu m, a mobile phase A is supercritical CO2, a mobile phase B is two organic solvents of methanol and ethanol (95: 5, v/v), and a phase B accounts for 20%. The column temperature of the polysaccharide derivative chiral chromatographic column is 40 ℃; the column pressure is 10 MPa; the detection wavelength is 254 nm; the flow rate is 2 mL/min; the injection volume was 5. mu.L.
See FIG. 4 for results. As can be seen from FIG. 4, the two enantiomeric chromatographic peaks of promethazine were separated effectively, and the elution order of the enantiomers of promethazine was investigated by a chiral spirit-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the correspondence between the isomers, the first peak being the dextroisomer of promethazine R-, and the second peak being the levoisomer of promethazine S-, and the chromatographic instrument showed a degree of separation of 1.089.
Example 5:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. The method adopts supercritical fluid chromatography as (SHIMADZU) Nexera UC SFC system, uses (Daicel) CHIRALPAK AD-H chiral chromatographic column, is a silica gel surface coated with amylose-tri (3, 5-dimethylphenyl carbamate) polysaccharide derivative chiral chromatographic column, and has the specification of 250mm multiplied by 4.6mm, the particle size of 5 mu m, and the mobile phase A is supercritical CO2The mobile phase B is methanol-acetonitrile two organic solvents (95: 5, v/v), and the B phase accounts for 20%. The column temperature of the polysaccharide derivative chiral chromatographic column is 40 ℃; the column pressure is 16 MPa; the detection wavelength is 254 nm; the flow rate is 1.5 mL/min; the injection volume was 5. mu.L.
See FIG. 5 for results. As can be seen from FIG. 5, the two enantiomeric chromatographic peaks of promethazine were separated effectively, and the elution order of the enantiomers of promethazine was investigated by a chiral laser-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the correspondence between the isomers, the first peak being the dextroisomer of promethazine R-, and the second peak being the levoisomer of promethazine S-, and the chromatographic instrument showed a degree of separation of 1.030.
Example 6:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. A supercritical fluid chromatograph is adopted as a (SHIMADZU) Nexera UC SFC system, a (Daicel) CHIRALPAK AD-H chiral chromatographic column is used, the chiral chromatographic column is a polysaccharide derivative type chiral chromatographic column of which the silica gel surface is coated with amylose-tri (3, 5-dimethylphenyl carbamate), the specification is 250mm multiplied by 4.6mm, the particle size is 5 mu m, a mobile phase A is supercritical CO2, a mobile phase B is two organic solvents of methanol and acetonitrile (80: 20, v/v), and a phase B accounts for 13%. The column temperature of the polysaccharide derivative chiral chromatographic column is 45 ℃; the column pressure is 11 MPa; the detection wavelength is 254 nm; the flow rate is 2.5 mL/min; the injection volume was 5. mu.L.
See FIG. 6 for results. As can be seen from FIG. 6, the two enantiomeric chromatographic peaks of promethazine were separated effectively, and the elution order of the enantiomers of promethazine was investigated by a chiral laser-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the correspondence between the isomers, the first peak was the dextroisomer of promethazine R-, the second peak was the levoisomer of promethazine S-, and the chromatographic resolution was 0.632.
Example 7:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. A supercritical fluid chromatograph is adopted as a (SHIMADZU) Nexera UC SFC system, a (Daicel) CHIRALPAK AD-H chiral chromatographic column is used, the chiral chromatographic column is a silica gel surface coated with amylose-tri (3, 5-dimethylphenyl carbamate) polysaccharide derivative type chiral chromatographic column, the specification is 250mm multiplied by 4.6mm, the particle size is 5 mu m, a mobile phase A is supercritical CO2, a mobile phase B is two organic solvents of methanol-isopropanol (85: 15, v/v), and a phase B accounts for 25%. The column temperature of the polysaccharide derivative chiral chromatographic column is 31 ℃; the column pressure is 12 MPa; the detection wavelength is 254 nm; the flow rate is 2 mL/min; the injection volume was 5. mu.L.
See FIG. 7 for results. As can be seen from FIG. 7, the two enantiomeric chromatographic peaks of promethazine were separated effectively, and the elution order of the enantiomers of promethazine was investigated by a chiral laser-MP type optical rotation detector (IBZ Messtech-nik, Germany) to determine the correspondence between the isomers, the first peak was the dextroisomer of promethazine R-, the second peak was the levoisomer of promethazine S-, and the chromatographic instrument showed a resolution of 2.097.
Comparative example:
weighing a certain amount of promethazine reference substance, dissolving with methanol and fixing volume, and preparing promethazine test sample solution. A supercritical fluid chromatograph is adopted as a (SHIMADZU) Nexera UC SFC system, a (Daicel) CHIRALPAK AD-H chiral chromatographic column is used, the chiral chromatographic column is a polysaccharide derivative type chiral chromatographic column of which the silica gel surface is coated with amylose-tri (3, 5-dimethylphenyl carbamate), the specification is 250mm multiplied by 4.6mm, the particle size is 5 mu m, the mobile phase A is supercritical CO2, the mobile phase B is methanol, and the phase B accounts for 15%. The column temperature of the polysaccharide derivative chiral chromatographic column is 50 ℃; the column pressure is 15 MPa; the detection wavelength is 254 nm; the flow rate is 2 mL/min; the injection volume was 5. mu.L.
See FIG. 8 for results. As can be seen from fig. 8, the chromatographic peaks of the two enantiomers of promethazine were not separated efficiently, and the chromatogram showed a single peak, so the degree of separation was 0. In summary, the present application employs supercritical fluid chromatography and is effective in chiral resolution of promethazine under specific chromatographic conditions.
The separated dextro-isomer of promethazine R-and levorotatory isomer of promethazine S-can be used for subsequent practical industrial application, for example, the difference of drug effects of dextro-isomer of promethazine R-and levorotatory isomer of promethazine S-is very large: the dextro-isomer of promethazine R-has stronger anti-osteoporosis effect than the racemic modification and the levo-isomer of promethazine S-; the dextrorotatory form of promethazine R-is effective in inhibiting osteoclasts; the dextrorotatory form of promethazine R-significantly reduced IL-6 production by histamine-stimulated cells compared to the levorotatory form of promethazine S-. It should be noted that the embodiments of the present invention have been described in terms of preferred embodiments, and not by way of limitation, and that those skilled in the art can make modifications and variations of the embodiments described above without departing from the spirit of the invention.
Claims (10)
1. A method for chiral resolution of promethazine, comprising the steps of:
(1) preparing a test solution: weighing a certain amount of promethazine reference substance (Beijing Bailingwei science and technology Co., Ltd.), and dissolving the promethazine reference substance by using an organic solution to prepare a promethazine test sample solution with the concentration of 10-30 mg/ml; and
(2) chiral resolution was performed using supercritical chromatography: separating promethazine enantiomer in the promethazine sample test solution by supercritical chromatography, wherein the stationary phase is polysaccharide derivative chiral chromatographic column, the ultraviolet wavelength is 254nm, the mobile phase A is supercritical fluid, the mobile phase B is organic solvent, the column temperature is 30-45 deg.C, the column pressure is 10-20MPa, the column pressure is constant pressure, and the flow rate is 1-3 ml/min.
2. The method for chiral resolution of promethazine according to claim 1, wherein the organic solvent in step (1) and step (2) is one or more selected from methanol, ethanol, acetonitrile, and isopropanol.
3. The method of chiral resolution of promethazine of claim 1, wherein in step (1) the concentration of the promethazine test solution is 20 mg/ml.
4. The method for chiral resolution of promethazine according to claim 2, wherein the ratio of mobile phase a to mobile phase B in step (2) is 10-20% by volume.
5. The method for chiral resolution of promethazine according to claim 4, wherein the volume ratio of the organic solvent in mobile phase A and mobile phase B in step (2) is 15%, the organic solvent comprises methanol and isopropanol, and the volume ratio is methanol: isopropanol-9: 1.
6. The method of chiral resolution of promethazine according to claim 1, wherein the polysaccharide derivative in step (2) is amylose-tris (3, 5-dimethylphenylcarbamate).
7. The method of chiral resolution of promethazine of claim 1, wherein the supercritical fluid in step (2) is supercritical carbon dioxide.
8. The method of chiral resolution of promethazine of claim 1, wherein the flow rate in step (2) is 2 ml/min.
9. The method of chiral resolution of promethazine of claim 1, wherein the column pressure in step (2) is 10 MPa.
10. The method of chiral resolution of promethazine of claim 1, wherein the column temperature in step (2) is 35 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011387808.1A CN112480028B (en) | 2020-12-01 | 2020-12-01 | Method for chiral resolution of promethazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011387808.1A CN112480028B (en) | 2020-12-01 | 2020-12-01 | Method for chiral resolution of promethazine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112480028A true CN112480028A (en) | 2021-03-12 |
| CN112480028B CN112480028B (en) | 2023-03-17 |
Family
ID=74938801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011387808.1A Active CN112480028B (en) | 2020-12-01 | 2020-12-01 | Method for chiral resolution of promethazine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112480028B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114230541A (en) * | 2021-12-17 | 2022-03-25 | 浙江省柑橘研究所 | Manual naringenin splitting method and absolute configuration determining method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106732475A (en) * | 2016-12-06 | 2017-05-31 | 青岛大学 | A kind of HPLC chiral stationary phases and its preparation method and application |
| CN106883322A (en) * | 2017-03-08 | 2017-06-23 | 天津大学 | The preparation of polynary cyclodextrin and its application in CE chiral analysis |
| CN111495341A (en) * | 2020-05-09 | 2020-08-07 | 中南民族大学 | Preparation and application of novel amphoteric chiral selector CEC monolithic column |
-
2020
- 2020-12-01 CN CN202011387808.1A patent/CN112480028B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106732475A (en) * | 2016-12-06 | 2017-05-31 | 青岛大学 | A kind of HPLC chiral stationary phases and its preparation method and application |
| CN106883322A (en) * | 2017-03-08 | 2017-06-23 | 天津大学 | The preparation of polynary cyclodextrin and its application in CE chiral analysis |
| CN111495341A (en) * | 2020-05-09 | 2020-08-07 | 中南民族大学 | Preparation and application of novel amphoteric chiral selector CEC monolithic column |
Non-Patent Citations (2)
| Title |
|---|
| CAROLINE WEST ET AL.: "Insights into chiral recognition mechanisms in supercritical fluid chromatography. II. Factors contributing to enantiomer separation on tris-(3,5-dimethylphenylcarbamate) of amylose and cellulose stationary phases", 《 JOURNAL OF CHROMATOGRAPHY A》 * |
| 邓惠敏等: "《超临界流体色谱技术》", 31 December 2019 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114230541A (en) * | 2021-12-17 | 2022-03-25 | 浙江省柑橘研究所 | Manual naringenin splitting method and absolute configuration determining method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112480028B (en) | 2023-03-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| West | Enantioselective separations with supercritical fluids-review | |
| McCalley | Analysis of the Cinchona alkaloids by high-performance liquid chromatography and other separation techniques | |
| CN101475530A (en) | Method for separating and purifying cisatracurium besylate by preparative liquid chromatography | |
| Wei et al. | Enantioseparation of lomefloxacin hydrochloride by high-speed counter-current chromatography using sulfated-β-cyclodextrin as a chiral selector | |
| Kirkland | Optimization of chiral selectivity on cellulose-based high-performance liquid chromatographic columns using aprotic mobile-phase modifiers | |
| CN112480028B (en) | Method for chiral resolution of promethazine | |
| Chankvetadze et al. | Enantioseparations using cellulose tris (3, 5-dichlorophenylcarbamate) during high-performance liquid chromatography with analytical and capillary columns potential for screening of chiral compounds | |
| Sun et al. | Alkaloid purification using rosin‐based polymer‐bonded silica stationary phase in HPLC | |
| CN106226427A (en) | A kind of supercritical fluid chromatography quickly splits the method for aranidipine racemic modification | |
| Kunath et al. | Diastereomeric and enantiomeric separation of monoesters prepared from meso-cyclopentanediols and racemic carboxylic acids on a silica phase and on amylose and cellulose chiral stationary phases | |
| CN107703235B (en) | Supercritical fluid chromatographic separation method for lenalidomide enantiomer | |
| Zhai et al. | Development and validation of HPLC methods for enantioseparation of mirtazapine enantiomers at analytical and semipreparative scale using polysaccharide chiral stationary phases | |
| Zhang et al. | Enantiomeric separation of 1, 4-dihydropyridines by liquid-phase microextraction with supercritical fluid chromatography | |
| CN100348595C (en) | Simulated moving bed chromatography separating method of omeprazole antimer | |
| CN108362789B (en) | High performance liquid chromatography detection method for abamectin sodium optical isomer | |
| Kumano et al. | Enantioseparation on Riboflavin derivatives chemically bonded to silica gel as chiral stationary phases for HPLC | |
| Pan et al. | Separation and identification of cis and trans isomers of 2-butene-l, 4-diol and lafutidine by HPLC and LC-MS | |
| Toribio et al. | Semipreparative chiral supercritical fluid chromatography in the fractionation of lansoprazole and two related antiulcer drugs enantiomers | |
| Yan et al. | Supercritical fluid chromatography and steady‐state recycling: Phase appropriate technologies for the resolutions of pharmaceutical intermediates in the early drug development stage | |
| CN112979511B (en) | Method for analyzing and preparing tert-butyl sulfinamide enantiomer by using HPLC | |
| US5641404A (en) | Process for the separation of enantiomers | |
| CN104826619A (en) | Application of bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral analysis and/or separation of sertraline hydrochloride intermediate (+/-)-Tetralone | |
| Cass et al. | Carbohydrate carbamate coated onto microporous silica: Application to chiral analysis of commercial pharmaceutical drugs | |
| CN114874206B (en) | Separation method of cis isomer of anisodamine | |
| CN113917027B (en) | Optical isomer separation detection method of avanafil and intermediate 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |