CN113899831B - Liquid chromatography detection method for tofacitinib citrate starting material - Google Patents
Liquid chromatography detection method for tofacitinib citrate starting material Download PDFInfo
- Publication number
- CN113899831B CN113899831B CN202111180339.0A CN202111180339A CN113899831B CN 113899831 B CN113899831 B CN 113899831B CN 202111180339 A CN202111180339 A CN 202111180339A CN 113899831 B CN113899831 B CN 113899831B
- Authority
- CN
- China
- Prior art keywords
- starting material
- tofacitinib citrate
- compound
- liquid chromatography
- detected
- 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.)
- Active
Links
Classifications
-
- 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
-
- 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
-
- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The liquid chromatographic detection method of the tofacitinib citrate initial material comprises the steps of firstly injecting a solution to be detected prepared from the tofacitinib citrate initial material into a high-performance liquid chromatographic column, then carrying out isocratic elution by using a mobile phase A, and finally detecting under an ultraviolet detector. The method can realize complete separation of the target material from the enantiomer and diastereoisomer, and has good separation effect, simple operation and high sensitivity.
Description
Technical Field
The invention belongs to the technical field of analytical chemistry, and particularly relates to a liquid chromatography detection method of a tofacitinib citrate starting material, which is suitable for separating a target material from enantiomers and diastereomers thereof, and has the advantages of simple operation, high separation degree, high sensitivity and good accuracy.
Background
Tofacitinib citrate is an oral protein tyrosine kinase inhibitor for the treatment of rheumatoid arthritis patients. The starting material 1-benzyl-4-methyl-3-methylaminopiperidine dihydrochloride for synthesizing tofacitinib citrate has two chiral centers and RR, RS, SR, SS optical isomers, wherein RR configuration and SS configuration are a pair of enantiomers, RS configuration and SR configuration are diastereomers, only the 1-benzyl-4-methyl-3-methylaminopiperidine dihydrochloride in RR configuration is the target material for effectively synthesizing tofacitinib citrate, and in the prior art, the commercially purchased starting material contains at least one optical isomer impurity in RS, SR and SS configurations besides the RR configuration, so that the separation of the target material from the enantiomers and diastereomers thereof is difficult to realize simultaneously under the condition of conventional liquid chromatography.
Disclosure of Invention
The invention aims to overcome the problems in the prior art and provide a liquid chromatography detection method for tofacitinib citrate starting material capable of separating enantiomers and diastereomers simultaneously.
In order to achieve the above object, the present invention provides the following technical solutions:
a liquid chromatography detection method of a tofacitinib citrate starting material, which comprises the following steps: firstly, injecting a solution to be detected prepared from a tofacitinib citrate starting material into a high performance liquid chromatographic column, then performing isocratic elution by using a mobile phase A, and finally, detecting by an ultraviolet detector;
the high performance liquid chromatography column is a normal phase chiral chromatography column taking cellulose-tris- (4-chloro-3-methylphenyl carbamate) as a filler, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 65-90:2-9:8-26:0.02-0.07:0.02-0.07, the tofacitinib citrate starting material comprises a target material and isomers of the target material, and the structural formula of the target material is as follows:
the isomer comprises at least one of enantiomer, compound I and compound II, and the enantiomer has the structural formula:
the compound I and the compound II are diastereoisomers, and the structural formula of the compound I is as follows:
the structural formula of the compound II is as follows:
the concentration of the tofacitinib citrate starting material in the solution to be detected is 200-2000 mug/ml.
The ultraviolet light wavelength in the ultraviolet detector is 210-220nm.
The flow rate of the mobile phase A is 0.7-0.9ml/min, and the column temperature of the high performance liquid chromatographic column is 15-25 ℃.
The solvent in the solution to be detected is ethanol.
Compared with the prior art, the invention has the beneficial effects that:
the high performance liquid chromatographic column adopted in the liquid chromatographic detection method of the tofacitinib citrate starting material is a normal phase chiral chromatographic column taking cellulose-tris- (4-chloro-3-methylphenyl carbamate) as a filler, and the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 65-90:2-9:8-26:0.02-0.07:0.02-0.07. Therefore, the invention can realize the complete separation of the target material from the enantiomer and diastereoisomer, and has good separation effect, simple operation and high sensitivity.
Drawings
FIG. 1 is an HPLC chart of example 1.
FIG. 2 is an HPLC chart of example 2.
FIG. 3 is an HPLC chart of example 3.
Fig. 4 is an HPLC profile of example 4.
Fig. 5 is an HPLC profile of example 5.
FIG. 6 is an HPLC chart of example 6.
FIG. 7 is an HPLC chart of example 7.
FIG. 8 is an HPLC chart of example 8.
Fig. 9 is an HPLC profile of example 9.
Fig. 10 is an HPLC profile of comparative example 1.
FIG. 11 is an HPLC chart of comparative example 2.
FIG. 12 is an HPLC chart of comparative example 3.
FIG. 13 is an HPLC chart of detection example 1.
FIG. 14 is an HPLC chart of detection example 2.
FIG. 15 is an HPLC chart of detection example 3.
FIG. 16 is an HPLC chart of detection example 4.
FIG. 17 is an HPLC chart of detection example 5.
Detailed Description
The invention is further described below in connection with the following detailed description.
A liquid chromatography detection method of a tofacitinib citrate starting material, which comprises the following steps: firstly, injecting a solution to be detected prepared from a tofacitinib citrate starting material into a high performance liquid chromatographic column, then performing isocratic elution by using a mobile phase A, and finally, detecting by an ultraviolet detector;
the high performance liquid chromatography column is a normal phase chiral chromatography column taking cellulose-tris- (4-chloro-3-methylphenyl carbamate) as a filler, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 65-90:2-9:8-26:0.02-0.07:0.02-0.07, the tofacitinib citrate starting material comprises a target material and isomers of the target material, and the structural formula of the target material is as follows:
the isomer comprises at least one of enantiomer, compound I and compound II, and the enantiomer has the structural formula:
the compound I and the compound II are diastereoisomers, and the structural formula of the compound I is as follows:
the structural formula of the compound II is as follows:
the concentration of the tofacitinib citrate starting material in the solution to be detected is 200-2000 mug/ml.
The ultraviolet light wavelength in the ultraviolet detector is 210-220nm.
The flow rate of the mobile phase A is 0.7-0.9ml/min, and the column temperature of the high performance liquid chromatographic column is 15-25 ℃.
The solvent in the solution to be detected is ethanol.
Example 1:
the liquid chromatography detection method for the tofacitinib citrate starting material is adopted to detect the solution to be detected, and the method specifically comprises the following steps:
step one, preparing each sample solution:
1. precisely measuring 10mg of starting material in a volumetric flask, adding ethanol for dissolution and diluting to 10ml to obtain a starting material sample solution, wherein the starting material is purchased from Shanghai Bose medical science and technology Co., ltd, the starting material is a mixture of a target material, a compound I and a compound II, and CAS Number of the starting material is 1062580-52-2;
2. firstly precisely measuring 5mg of enantiomer standard substance in a volumetric flask, adding ethanol for dissolution and dilution to 50ml to obtain enantiomer stock solution, then precisely measuring 1ml of enantiomer stock solution in another volumetric flask, adding ethanol for dilution to 10ml to obtain enantiomer test substance solution;
3. firstly precisely measuring 5mg of a compound I standard substance in a volumetric flask, adding ethanol for dissolving and diluting to 50ml to obtain a compound I stock solution, then precisely measuring 1ml of the compound I stock solution in another volumetric flask, adding ethanol for diluting to 20ml to obtain a compound I sample solution;
4. firstly precisely measuring 5mg of compound II standard substance in a volumetric flask, adding ethanol for dissolution and dilution to 50ml to obtain compound II stock solution, then precisely measuring 1ml of compound II stock solution in another volumetric flask, adding ethanol for dilution to 20ml to obtain compound II sample solution;
5. firstly, precisely measuring 10mg of a starting material in a volumetric flask, adding ethanol to dissolve the starting material, then sequentially adding 1ml of an enantiomer stock solution, 0.5ml of a compound I stock solution and 0.5ml of a compound II stock solution, and finally adding ethanol again to dilute the mixture to 10ml to obtain a mixed sample solution;
the structural formulas of the target material, enantiomer, compound I and compound II are shown in table 1:
TABLE 1 structural formulas of target materials, enantiomers, compounds I and II
Injecting a solution to be detected into a high performance liquid chromatography column, then performing isocratic elution by using a mobile phase A, and finally performing detection under an ultraviolet detector, wherein the solution to be detected is a mixed sample solution, the high performance liquid chromatography column is a Filman Chiral MX (2) column taking cellulose-tris- (4-chloro-3-methylphenyl carbamate) as a filler, the specification is 250 multiplied by 4.6mm multiplied by 5 mu, the column temperature is 20 ℃, the sample injection amount is 10 mu l, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to a volume ratio of 90:2:8:0.02:0.02, the flow rate of the mobile phase A is 0.8ml/min, the ultraviolet wavelength of the ultraviolet detector is 210nm, the detected HPLC chart is shown in figure 1, and the retention time, the theoretical plate number, the tailing factor and the minimum separation degree of ASIM2 are shown in Table 2.
Example 2:
the difference from example 1 is that:
in the second step, the mobile phase a is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to a volume ratio of 70:8:22:0.06:0.06, the detected HPLC diagram is shown in fig. 2, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in table 2.
Example 3:
the difference from example 1 is that:
in the second step, the mobile phase a is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to a volume ratio of 65:9:26:0.07:0.07, the detected HPLC diagram is shown in fig. 3, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in table 2.
Example 4:
the difference from example 1 is that:
in the second step, the mobile phase a is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to a volume ratio of 80:5:15:0.04:0.04, the column temperature of the high performance liquid chromatography column is 15 ℃, the detected HPLC diagram is shown in fig. 4, and the minimum values of the retention time, theoretical plate number, tailing factor and separation degree of 1401ASIM2 are shown in table 2.
Example 5:
the difference from example 4 is that:
in the second step, the column temperature of the high performance liquid chromatography column is 25 ℃, the detected HPLC chart is shown in fig. 5, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in table 2.
Example 6:
the difference from example 1 is that:
in the second step, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 80:5:15:0.04:0.04, the flow rate of the mobile phase A is 0.76ml/min, the detected HPLC chart is shown in fig. 6, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in table 2.
Example 7:
the difference from example 6 is that:
in the second step, the flow rate of the mobile phase A is 0.84ml/min, the detected HPLC chart is shown in FIG. 7, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in Table 2.
Example 8:
the difference from example 1 is that:
in the second step, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 80:5:15:0.04:0.04, the ultraviolet wavelength of the ultraviolet detector is 215nm, the detected HPLC chart is shown in figure 8, and the retention time, theoretical plate number, tailing factor and separation degree minimum value of 1401ASIM2 are shown in table 2.
Example 9:
the difference from example 8 is that:
in the second step, the ultraviolet wavelength of the ultraviolet detector is 220nm, the detected HPLC diagram is shown in fig. 9, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in table 2.
Comparative example 1:
the difference from example 1 is that:
in the second step, the high performance liquid chromatography column is a large-scale race AD-H column taking amylose-tris- (3, 5-dimethylphenylcarbamate) as a filler, the specification is 4.6X250 mm and 5 μm, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 80:5:15:0.04:0.04, the detected HPLC chart is shown in figure 10, and the retention time, theoretical plate number, tailing factor and minimum separation degree of 1401ASIM2 are shown in table 2.
Comparative example 2:
the difference from comparative example 1 is that:
in the second step, the HPLC column is a macelix OZ-H column using cellulose-tris- (3-chloro-4-methylphenyl carbamate) as a filler, the detected HPLC profile is shown in fig. 11, and the retention time, theoretical plate number, tailing factor, and minimum separation degree of 1401ASIM2 are shown in table 2.
Comparative example 3:
the difference from comparative example 1 is that:
in the second step, the high performance liquid chromatography column is a phenanthrene portal MX (2) column using cellulose-tris- (4-chloro-3-methylphenyl carbamate) as a filler, the mobile phase a is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to a volume ratio of 95:1:4:0.01:0.01, the detected HPLC spectrum is shown in fig. 12, and the retention time, theoretical plate number, tailing factor and separation degree minimum values of 1401ASIM2 are shown in table 2.
Detection example 1:
the difference from example 1 is that:
in the second step, the solution to be detected is a sample solution of a starting material, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to a volume ratio of 80:5:15:0.04:0.04, the detected HPLC chart is shown in fig. 13, the retention time, theoretical plate number, tailing factor and separation degree minimum value of 1401ASIM2 are shown in table 2, and the relative retention time of 1401ASIM2 is shown in table 3.
Detection example 2:
the difference from the test example 1 is that:
in the second step, the solution to be detected is an enantiomer test solution, the detected HPLC diagram is shown in fig. 14, and the retention time and the relative retention time of 1401ASIM21 are shown in table 3.
Detection example 3:
the difference from the test example 1 is that:
in the second step, the solution to be detected is a sample solution of the compound I, the detected HPLC chart is shown in FIG. 15, and the retention time and the relative retention time of 1401ASIM22 are shown in Table 3.
Detection example 4:
the difference from the test example 1 is that:
in the second step, the solution to be detected is a compound II test sample solution, the detected HPLC chart is shown in fig. 16, and the retention time and the relative retention time of 1401ASIM23 are shown in table 3.
Detection example 5:
the difference from the test example 1 is that:
in the second step, the solution to be detected is a mixed sample solution, and the detected HPLC chart is shown in FIG. 17.
Data analysis:
table 2 retention time of 1401ASIM2 in each experiment
| Retention time (min) | Number of theoretical plates | Tailing factor | Minimum value of separation degree | |
| Example 1 | 16.101 | 9736 | 1.13 | 1.67 |
| Example 2 | 11.355 | 10179 | 1.09 | 1.78 |
| Example 3 | 9.435 | 9963 | 1.00 | 1.53 |
| Example 4 | 13.562 | 9595 | 1.11 | 1.80 |
| Example 5 | 12.873 | 10372 | 1.12 | 1.76 |
| Example 6 | 13.895 | 10096 | 1.13 | 1.91 |
| Example 7 | 12.731 | 9692 | 1.12 | 1.87 |
| Example 8 | 13.252 | 9714 | 1.14 | 1.86 |
| Example 9 | 13.252 | 10026 | 1.14 | 1.87 |
| Comparative example 1 | 5.008 | 2203 | 2.34 | 2.41 |
| Comparative example 2 | 9.591 | 5068 | 2.71 | Without any means for |
| Comparative example 3 | 23.880 | 8976 | 1.09 | 1.25 |
| Detection example 1 | 13.242 | 10100 | 1.12 | 1.94 |
TABLE 3 retention times and relative retention times of the substances
| Short for short | Retention time (min) | Relative retention time |
| 1401ASIM2 | 13.242 | 1.00 |
| 1401ASIM21 | 14.237 | 1.08 |
| 1401ASIM22 | 12.239 | 0.93 |
| 1401ASIM23 | 12.305 | 0.94 |
Referring to fig. 10-12, the main peak of 1401ASIM2 and the peak of solvent in comparative example 1 are not separated, the main peak of 1401ASIM2 is detected only in comparative example 2, other peaks cannot be detected, the separation degree in comparative example 3 is only 1.25 (see table 2), which means that 1401ASIM2 and 1401ASIM21, 1401ASIM22 and 1401ASIM23 cannot be completely separated, and all three cannot meet the separation requirement, see fig. 1-9, and the separation degree in examples 1-9 of the liquid chromatography detection method using the tofacitinib citrate starting material in the invention is greater than 1.5 (see table 2), which means that the method can realize complete separation of 1401ASIM2 and 1401ASIM21, 1401ASIM22 and 1401ASIM23, and has good separation effect, simple operation and high sensitivity.
Claims (5)
1. A liquid chromatography detection method of a tofacitinib citrate starting material is characterized in that:
the detection method comprises the following steps: firstly, injecting a solution to be detected prepared from a tofacitinib citrate starting material into a high performance liquid chromatographic column, then performing isocratic elution by using a mobile phase A, and finally, detecting by an ultraviolet detector;
the high performance liquid chromatography column is a normal phase chiral chromatography column taking cellulose-tris- (4-chloro-3-methylphenyl carbamate) as a filler, the mobile phase A is a mixed solution obtained by mixing n-hexane, ethanol, methanol, diethylamine and trifluoroacetic acid according to the volume ratio of 65-90:2-9:8-26:0.02-0.07:0.02-0.07, the tofacitinib citrate starting material comprises a target material and isomers of the target material, and the structural formula of the target material is as follows:
the isomer comprises at least one of enantiomer, compound I and compound II, and the enantiomer has the structural formula:
the compound I and the compound II are diastereoisomers, and the structural formula of the compound I is as follows:
the structural formula of the compound II is as follows:
2. the method for liquid chromatography detection of tofacitinib citrate starting material according to claim 1, wherein the method comprises the steps of: the concentration of the tofacitinib citrate starting material in the solution to be detected is 200-2000 mug/ml.
3. The method for liquid chromatography detection of tofacitinib citrate starting material according to claim 1 or 2, characterized in that: the ultraviolet light wavelength in the ultraviolet detector is 210-220nm.
4. The method for liquid chromatography detection of tofacitinib citrate starting material according to claim 1 or 2, characterized in that: the flow rate of the mobile phase A is 0.7-0.9ml/min, and the column temperature of the high performance liquid chromatographic column is 15-25 ℃.
5. The method for liquid chromatography detection of tofacitinib citrate starting material according to claim 1 or 2, characterized in that: the solvent in the solution to be detected is ethanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111180339.0A CN113899831B (en) | 2021-10-11 | 2021-10-11 | Liquid chromatography detection method for tofacitinib citrate starting material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111180339.0A CN113899831B (en) | 2021-10-11 | 2021-10-11 | Liquid chromatography detection method for tofacitinib citrate starting material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113899831A CN113899831A (en) | 2022-01-07 |
| CN113899831B true CN113899831B (en) | 2023-08-15 |
Family
ID=79191158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111180339.0A Active CN113899831B (en) | 2021-10-11 | 2021-10-11 | Liquid chromatography detection method for tofacitinib citrate starting material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113899831B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016050208A1 (en) * | 2014-10-01 | 2016-04-07 | 厦门赛诺邦格生物科技有限公司 | Bio-related substance modified by multifunctionalized polyethylene glycol derivative |
| CN107064350A (en) * | 2017-04-11 | 2017-08-18 | 山东裕欣药业有限公司 | Method for detecting suspected genotoxic impurity of tofacitinib citrate |
| CN109206361A (en) * | 2017-06-29 | 2019-01-15 | 意大利合成制造有限公司 | The improvement preparation method of useful intermediates chirality 3- amino piperidine for tropsch imatinib preparation |
| CN111751453A (en) * | 2019-03-27 | 2020-10-09 | 南京格亚医药科技有限公司 | Analysis method of (3R, 4R) -N, 4-dimethyl-1- (phenylmethyl) -3-piperidinamine salt |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019040706A1 (en) * | 2017-08-24 | 2019-02-28 | Aclaris Therapeutics, Inc. | Compositions and methods for treatment of vitiligo |
| CN112213402B (en) * | 2019-07-10 | 2022-11-04 | 江苏晶立信医药科技有限公司 | Method for detecting (3R, 4R) -1-benzyl-N, 4-dimethylpiperidine-3-amine dihydrochloride and isomer thereof |
| CN112697906B (en) * | 2020-12-10 | 2022-09-13 | 上海博悦生物科技有限公司 | Method for detecting chiral intermediate and enantiomer of tofacitinib |
-
2021
- 2021-10-11 CN CN202111180339.0A patent/CN113899831B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016050208A1 (en) * | 2014-10-01 | 2016-04-07 | 厦门赛诺邦格生物科技有限公司 | Bio-related substance modified by multifunctionalized polyethylene glycol derivative |
| CN107064350A (en) * | 2017-04-11 | 2017-08-18 | 山东裕欣药业有限公司 | Method for detecting suspected genotoxic impurity of tofacitinib citrate |
| CN109206361A (en) * | 2017-06-29 | 2019-01-15 | 意大利合成制造有限公司 | The improvement preparation method of useful intermediates chirality 3- amino piperidine for tropsch imatinib preparation |
| CN111751453A (en) * | 2019-03-27 | 2020-10-09 | 南京格亚医药科技有限公司 | Analysis method of (3R, 4R) -N, 4-dimethyl-1- (phenylmethyl) -3-piperidinamine salt |
Non-Patent Citations (1)
| Title |
|---|
| 枸橼酸托法替尼的合成与精制分离及放大工艺研究;张喜;中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑(第01期);B016-1262 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113899831A (en) | 2022-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110596268B (en) | Separation and detection method for isomers in loratadine racemate | |
| CN110988230A (en) | Liquid chromatography separation detection method for flurbiprofen axetil enantiomer and impurity A | |
| CN111189947B (en) | Analysis method for separating and detecting propane fumarate tenofovir disoproxil isomer | |
| CN112697906B (en) | Method for detecting chiral intermediate and enantiomer of tofacitinib | |
| CN107402259B (en) | Method for detecting chiral isomer in carfilzomib | |
| CN110849980A (en) | Method for detecting content of enantiomer in isopropyl L-alanine | |
| CN107894470A (en) | A kind of detection method of Aprepitant intermediate | |
| CN107941970A (en) | The method for separating and detecting of D D-pHPGs and its enantiomter | |
| CN109856255B (en) | Analysis method for controlling isomer impurity content of ticagrelor intermediate | |
| CN113899831B (en) | Liquid chromatography detection method for tofacitinib citrate starting material | |
| CN116642970A (en) | Sample pretreatment method for simultaneously detecting 6 drug concentrations in blood | |
| CN112986478B (en) | Determination method for screening and quantitatively analyzing preservative components in compound liquorice tablets | |
| CN113820417B (en) | Method for separating and measuring piroxicam and impurities thereof | |
| CN112213407B (en) | Detection method of levoornidazole related substances | |
| CN109085255B (en) | Method for analyzing and preparing 3- (N-p-toluenesulfonyl-L-alanyloxy) -5-phenylpyrrole and enantiomer thereof by using HPLC method | |
| CN115112784A (en) | Method for detecting enantiomer in tolterodine tartrate | |
| CN114324702A (en) | Isomer detection method of carfilzomib intermediate | |
| CN110824038A (en) | Liquid chromatography analysis method of 2,3,4, 6-tetra-O-trimethylsilyl-D-gluconolactone | |
| CN112881565B (en) | HPLC detection method of triphenyldiamidine related substances | |
| CN111257441B (en) | Method for detecting impurities in parecoxib sodium synthesis process | |
| CN113419006B (en) | Liquid phase analysis method of aprepitant optical isomer | |
| CN117451858A (en) | Detection method and application of pitavastatin calcium enantiomer | |
| CN115902032A (en) | Analysis method for isomer in fragment 1 of raw material for preparing eldecalcitol | |
| CN113311097A (en) | Method for determining content of impurities in sofosbuvir enantiomer | |
| CN117871705A (en) | Analysis method of estradiol valerate tablet related substances |
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 |