CN114660214A - Liquid chromatography detection method of semaglutide and application thereof - Google Patents
Liquid chromatography detection method of semaglutide and application thereof Download PDFInfo
- Publication number
- CN114660214A CN114660214A CN202210152353.8A CN202210152353A CN114660214A CN 114660214 A CN114660214 A CN 114660214A CN 202210152353 A CN202210152353 A CN 202210152353A CN 114660214 A CN114660214 A CN 114660214A
- Authority
- CN
- China
- Prior art keywords
- semaglutide
- liquid chromatography
- chromatographic column
- detection method
- impurities
- 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
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 229950011186 semaglutide Drugs 0.000 title claims abstract description 42
- 108010060325 semaglutide Proteins 0.000 title claims abstract description 42
- 238000001514 detection method Methods 0.000 title claims abstract description 29
- 238000004811 liquid chromatography Methods 0.000 title claims abstract description 28
- 239000012535 impurity Substances 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000010828 elution Methods 0.000 claims abstract description 11
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000011259 mixed solution Substances 0.000 claims abstract description 5
- 239000008055 phosphate buffer solution Substances 0.000 claims abstract description 5
- 230000005526 G1 to G0 transition Effects 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 10
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- UNXNGGMLCSMSLH-UHFFFAOYSA-N dihydrogen phosphate;triethylazanium Chemical compound OP(O)(O)=O.CCN(CC)CC UNXNGGMLCSMSLH-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 238000012856 packing Methods 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 claims description 2
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 235000019837 monoammonium phosphate Nutrition 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims 2
- 238000000926 separation method Methods 0.000 abstract description 12
- 239000003960 organic solvent Substances 0.000 abstract 1
- 239000012071 phase Substances 0.000 description 14
- 230000014759 maintenance of location Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 3
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 1
- -1 CN201910685612 Chemical compound 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
Images
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
- 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
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
A liquid chromatography detection method of semaglutide and application thereof belong to the technical field of pharmaceutical chemistry. The invention provides a liquid chromatography detection method of semaglutide, which comprises the following steps: phosphate buffer solution is used as a mobile phase A, a mixed solution of an organic solvent and water is used as a mobile phase B, a single chromatographic column is used as a stationary phase, a detector is an ultraviolet detector, and high performance liquid chromatography is adopted to carry out gradient elution on the semaglutide. The invention also provides application of the liquid chromatography detection method in detecting and identifying impurities generated in the production or storage process of semaglutide. The method can complete the liquid chromatography detection of the semaglutide only by using common liquid chromatography and only one chromatographic column, and the detected number is large, the separation degree is high, and most of the detection number reaches 1.5.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a liquid chromatography detection method of semaglutide and application thereof.
Background
Semaglutide (CAS number 900463-68-2) is a new generation of long-acting GLP-1 analogue developed and developed by Novonide company and used for treating type II diabetes, and the Semaglutide has the effects of reducing blood sugar, losing weight and protecting cardiovascular, and is the best medicament for reducing blood sugar and losing weight in the existing GLP-1 medicament.
During the production and storage of the polypeptide, a series of impurities are generated, for example, the following impurities are easily generated during the production and storage of the semaglutide: D-His1Racemic impurities, Des-Aib2Defective impurities, Plus-Gly4Impurities. The presence of these impurities can be detrimental to patient use and so a simple, rapid and feasible assay must be established to detect the quality of semaglutide.
Currently, a published technology for detecting semaglutide, such as CN201910685612, discloses an ultra-high performance liquid chromatography analysis method for semaglutide. However, the existing detection method has extremely high requirements on instrument equipment and chromatographic columns, the arrangement of the flow phase is complicated, and the separation degree of impurities and main peaks and impurities is low.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to design and provide a liquid chromatography detection method of semaglutide and application thereof. The invention provides a method for detecting semaglutide, which has good separation effect, strong operability and lower requirements on instruments and chromatographic columns aiming at the physicochemical characteristics of the semaglutide.
In order to realize the purpose, the invention adopts the following technical scheme:
a liquid chromatography detection method of semaglutide is characterized in that phosphate buffer solution is used as a mobile phase A, a mixed solution of an organic reagent and water is used as a mobile phase B, a single chromatographic column is used as a stationary phase, a detector is an ultraviolet detector, and high performance liquid chromatography is adopted for gradient elution of the semaglutide.
The liquid chromatography detection method of semaglutide is characterized in that the chromatographic column comprises a C18 reverse phase chromatographic column or a C8 reverse phase chromatographic column, preferably a C8 reverse phase chromatographic column.
The liquid chromatography detection method of the semaglutide is characterized in that the packing particle size of the chromatographic column is 3.5-10 mu m, and the preferable packing particle size is 3.5 mu m.
The liquid chromatography detection method of semaglutide is characterized in that the phosphate buffer solution comprises at least one of triethylamine phosphate, ammonium dihydrogen phosphate, dipotassium hydrogen phosphate and disodium hydrogen phosphate, preferably the phosphate buffer solution is triethylamine phosphate, and the organic reagent in the mobile phase B is at least one of acetonitrile, methanol, ethanol and isopropanol, preferably acetonitrile.
The liquid chromatography detection method of the semaglutide is characterized in that the volume ratio of an organic reagent to water in a mixed solution of the organic reagent and water is 7: 3-9: 1, and the volume ratio of the organic reagent to water is preferably 8: 2.
the liquid chromatography detection method of semaglutide is characterized in that the gradient range of the mobile phase B is 40-65%.
The liquid chromatography detection method of semaglutide is characterized in that the column temperature is 25-35 ℃, the preferred column temperature is 30 ℃, the flow rate is 0.4-0.8 mL/min, and the preferred flow rate is 0.7mL/min in the gradient elution process.
The liquid chromatography detection method of semaglutide is characterized in that the wavelength of the ultraviolet detector is 220 nm.
Any one of the liquid chromatography detection methods for semaglutide is applied to the detection and identification of impurities generated in the production or storage process of semaglutide.
The use of (A), wherein the impurity comprises D-His1Racemized impurities,Des-Aib2Defective impurities, Plus-Gly4Impurities.
Compared with the prior art, the invention has the following beneficial effects:
1. the prior art needs to use an ultra-high liquid phase method, and the method only needs to use common liquid chromatography.
2. In the prior art, chromatographic columns are used in combination, and the method only needs one chromatographic column.
3. The number of impurities which can be detected by the prior art is limited, the separation degree is not high, the number detected by the method is large, the separation degree is high, and most of the separation degree reaches 1.5.
Drawings
FIG. 1 shows example 1 in which the method is applied to detect a D-His-containing substance1And Plus-Gly4Chromatograms of semaglutide samples of two impurities;
FIG. 2 shows example 2 in which the method is applied to detect a compound containing D-His1、Des-Aib2And Plus-Gly4Chromatograms of a semaglutide sample of three impurities;
FIG. 3 shows the prior art method of comparative example 1 for detecting a composition containing D-His1And Plus-Gly4Chromatograms of a semaglutide sample of two impurities.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below, but the present invention is not to be construed as being limited to the implementable range thereof.
Example 1:
chromatographic conditions are as follows:
(a) the instrument comprises: agilent 1260 high performance liquid chromatograph.
(b) A chromatographic column: agilent C18 column, 4.6mm × 150mm, 3.5 μm.
(c) Detection wavelength: 220 nm.
(d) Flow rate: 0.7 mL/min.
(e) Sample introduction amount: 20 μ L.
(f) Column temperature: at 30 ℃.
(g) Collecting time: and (4) 46 min.
(i) A mobile phase A: 50mmol/L triethylamine phosphate (pH4.5); and the mobile phase B comprises methanol and water, wherein the ratio of the methanol to the water is 9: 1.
(j) Elution conditions: as in table 1 below.
TABLE 1 gradient elution
Separation effect: as shown in fig. 1 and table 2, 3 impurities were separated and the degrees of separation were all greater than 1.5. Wherein D-His is separated at a retention time of 9.185min1Racemizing impurities, and separating at retention time of 11.349min to obtain Plus-Gly4Impurities.
Table 2 example 1 high performance liquid chromatography test results
Example 2:
chromatographic conditions are as follows:
(a) the instrument comprises the following steps: agilent 1260 high performance liquid chromatograph.
(b) A chromatographic column: agilent C8 chromatographic column, 4.6mm × 150mm, 3.5 μm.
(c) Detection wavelength: 220 nm.
(d) Flow rate: 0.7 mL/min.
(e) Sample introduction amount: 20 μ L.
(f) Column temperature: at 30 ℃.
(g) Collecting time: and (4) 46 min.
(i) Mobile phase A: 50mmol/L triethylamine phosphate (pH 4.5); and the mobile phase B comprises acetonitrile and water, wherein the ratio of the acetonitrile to the water is 8: 2.
(j) Elution conditions: as in table 3 below.
TABLE 3 gradient elution
Separation effect: as shown in the figure2 and table 4, 4 impurities were separated and the degree of separation was greater than 1.5. Wherein D-His is separated at a retention time of 9.178min1Racemizing impurities, and separating at a retention time of 10.557min to obtain Des-Aib2The impurities are lost, and the obtained product is Plus-Gly when the retention time is 12.269min4Impurities.
Table 4 example 2 high performance liquid chromatography test results
Comparative example 1:
chromatographic conditions are as follows:
(a) the instrument comprises the following steps: ACQUITY CLASS-H (Wterse).
(b) A chromatographic column: the C8 column and the C4 column are connected in series.
(c) Detection wavelength: 214 nm.
(d) Flow rate: 0.3 mL/min.
(e) Sample introduction amount: 20 μ L.
(f) Column temperature: at 50 ℃.
(g) Collecting time: and (4) 120 min.
(i) Mobile phase A: a mixed aqueous solution of 10mmol/L sodium perchlorate and 1mmol/L potassium hexafluorophosphate, the pH being adjusted to 3.0 with perchloric acid; and the mobile phase B is acetonitrile.
(j) Elution conditions: as in table 5 below.
TABLE 5 gradient elution
Separation effect: as shown in fig. 3 and table 6, 3 impurities were separated and the degrees of separation were all less than 1.5. Wherein D-His is separated at a retention time of 18.759min1Racemizing impurities, and separating at retention time of 20.832min to obtain Des-Aib2The impurities are lost, and the impurities are separated at the retention time of 23.582min to obtain Plus-Gly4Impurities.
TABLE 6 detection results of HPLC of comparative example 1
Claims (10)
1. A liquid chromatography detection method of semaglutide is characterized in that phosphate buffer solution is used as a mobile phase A, a mixed solution of an organic reagent and water is used as a mobile phase B, a single chromatographic column is used as a stationary phase, a detector is an ultraviolet detector, and high performance liquid chromatography is adopted for gradient elution of the semaglutide.
2. The method for detecting semaglutide by liquid chromatography as claimed in claim 1, wherein said chromatographic column comprises a C18 reverse phase chromatographic column or a C8 reverse phase chromatographic column, preferably a C8 reverse phase chromatographic column.
3. The liquid chromatography detection method of semaglutide as claimed in claim 2, wherein the packing particle size of said chromatographic column is 3.5-10 μm, preferably 3.5 μm.
4. The method for detecting semaglutide by liquid chromatography as claimed in claim 1, wherein said phosphate buffer comprises at least one of triethylamine phosphate, ammonium dihydrogen phosphate, dipotassium hydrogen phosphate and disodium hydrogen phosphate, preferably the phosphate buffer is triethylamine phosphate, and said organic reagent is at least one of acetonitrile, methanol, ethanol and isopropanol, preferably acetonitrile.
5. The liquid chromatography detection method of semaglutide as claimed in claim 1, wherein the volume ratio of the organic reagent to water in the mixed solution of the organic reagent and water is 7: 3-9: 1, and the volume ratio of the organic reagent to water is preferably 8: 2.
6. The method for detecting semaglutide by liquid chromatography as claimed in claim 1, wherein the gradient of said mobile phase B is in the range of 40-65%.
7. The method for detecting semaglutide by liquid chromatography as claimed in claim 1, wherein the column temperature during said gradient elution is 25-35 ℃, preferably 30 ℃, and the flow rate is 0.4-0.8 mL/min, preferably 0.7 mL/min.
8. The method for detecting semaglutide by liquid chromatography as claimed in claim 1, wherein the wavelength of said ultraviolet detector is 220 nm.
9. Use of a liquid chromatography detection method of semaglutide as claimed in any of claims 1 to 8 for the detection and identification of impurities produced during production or storage of semaglutide.
10. The use of claim 9, wherein said impurity comprises D-His1Racemic impurities, Des-Aib2Defective impurities, Plus-Gly4Impurities.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210152353.8A CN114660214B (en) | 2022-02-18 | 2022-02-18 | Liquid chromatography detection method of semaglutin and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210152353.8A CN114660214B (en) | 2022-02-18 | 2022-02-18 | Liquid chromatography detection method of semaglutin and application thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114660214A true CN114660214A (en) | 2022-06-24 |
CN114660214B CN114660214B (en) | 2024-04-05 |
Family
ID=82028022
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210152353.8A Active CN114660214B (en) | 2022-02-18 | 2022-02-18 | Liquid chromatography detection method of semaglutin and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114660214B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115326956A (en) * | 2022-08-09 | 2022-11-11 | 成都普康生物科技有限公司 | Method for separating and detecting homologous impurities in Somalutide modifier |
CN116298027A (en) * | 2022-12-28 | 2023-06-23 | 江苏诺泰澳赛诺生物制药股份有限公司 | Liquid chromatography detection method and application of genotoxic impurities |
CN116425858A (en) * | 2023-03-01 | 2023-07-14 | 浙江大学 | Fluorescence-modified semaglutin derivative and preparation method and application thereof |
CN116500172A (en) * | 2023-06-29 | 2023-07-28 | 成都普康唯新生物科技有限公司 | Detection method of amine solvent in acidic substrate |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109456401A (en) * | 2018-12-03 | 2019-03-12 | 成都诺和晟泰生物科技有限公司 | A kind of synthetic method of Suo Malu peptide |
CN111050750A (en) * | 2017-08-24 | 2020-04-21 | 诺沃挪第克公司 | GLP-1 compositions and uses thereof |
WO2020190757A1 (en) * | 2019-03-15 | 2020-09-24 | Novetide Ltd. | Improved processes for the preparation of semaglutide |
CN112912100A (en) * | 2018-10-26 | 2021-06-04 | 诺和诺德股份有限公司 | Stable semaglutide compositions and uses thereof |
US20210252111A1 (en) * | 2020-02-18 | 2021-08-19 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
-
2022
- 2022-02-18 CN CN202210152353.8A patent/CN114660214B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111050750A (en) * | 2017-08-24 | 2020-04-21 | 诺沃挪第克公司 | GLP-1 compositions and uses thereof |
CN112912100A (en) * | 2018-10-26 | 2021-06-04 | 诺和诺德股份有限公司 | Stable semaglutide compositions and uses thereof |
CN109456401A (en) * | 2018-12-03 | 2019-03-12 | 成都诺和晟泰生物科技有限公司 | A kind of synthetic method of Suo Malu peptide |
WO2020190757A1 (en) * | 2019-03-15 | 2020-09-24 | Novetide Ltd. | Improved processes for the preparation of semaglutide |
US20210252111A1 (en) * | 2020-02-18 | 2021-08-19 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
Non-Patent Citations (3)
Title |
---|
JINHUA ZHANG 等: "Efficient synthesis of Aib8-Arg34-GLP-1 (7–37) by liquid-phase fragment condensation", JOURNAL OF PEPTIDE SCIENCE : AN OFFICIAL PUBLICATION OF THE EUROPEAN PEPTIDE SOCIETY, vol. 28, no. 09, pages 3407 * |
MERUGU MANASA 等: "Stability Indicating Method Development and Validation of Semaglutide by RP-HPLC in Pharmaceutical substance and Pharmaceutical Product", RESEARCH J. PHARM. AND TECH, vol. 14, no. 03, pages 1385 - 1389 * |
SUBHA HARIKA PENMETSA 等: "METHOD DEVELOPMENT AND VALIDATION OF RP-UPLC METHOD FOR THE DETERMINATION OF SEMAGLUTIDE IN BULK AND PHARMACEUTICAL DOSAGE FORM", INTERNATIONAL JOURNAL OF RESEARCH AND ANALYTICAL REVIEWS, vol. 05, no. 04, pages 534 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115326956A (en) * | 2022-08-09 | 2022-11-11 | 成都普康生物科技有限公司 | Method for separating and detecting homologous impurities in Somalutide modifier |
CN115326956B (en) * | 2022-08-09 | 2024-02-27 | 成都普康生物科技有限公司 | Separation detection method for homolog impurities in cable Ma Lutai modifier |
CN116298027A (en) * | 2022-12-28 | 2023-06-23 | 江苏诺泰澳赛诺生物制药股份有限公司 | Liquid chromatography detection method and application of genotoxic impurities |
CN116425858A (en) * | 2023-03-01 | 2023-07-14 | 浙江大学 | Fluorescence-modified semaglutin derivative and preparation method and application thereof |
CN116425858B (en) * | 2023-03-01 | 2024-04-19 | 浙江大学 | Fluorescence-modified semaglutin derivative and preparation method and application thereof |
CN116500172A (en) * | 2023-06-29 | 2023-07-28 | 成都普康唯新生物科技有限公司 | Detection method of amine solvent in acidic substrate |
CN116500172B (en) * | 2023-06-29 | 2023-09-05 | 成都普康唯新生物科技有限公司 | Detection method of amine solvent in acidic substrate |
Also Published As
Publication number | Publication date |
---|---|
CN114660214B (en) | 2024-04-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114660214A (en) | Liquid chromatography detection method of semaglutide and application thereof | |
Koizumi et al. | Separation of cyclic (1→ 2)-β-D-glucans (cyclosophoraoses) produced by Agrobacterium and Rhizobium, and determination of their degree of polymerization by high-performance liquid chromatography | |
CN112684089A (en) | Method for separating and determining carnitine enantiomer in health food based on ultra-high performance synthetic phase chromatography technology | |
Xun et al. | Simultaneous determination of eight alkaloids and oleandrin in herbal cosmetics by dispersive solid‐phase extraction coupled with ultra high performance liquid chromatography and tandem mass spectrometry | |
Pan et al. | Preparative separation of isoquinoline alkaloids from Corydalis impatiens using a middle‐pressure chromatogram isolated gel column coupled with two‐dimensional liquid chromatography | |
Naidong et al. | Development and validation of a high-performance liquid chromatographic method for the quantitation of warfarin enantiomers in human plasma | |
CN115184497A (en) | Method for measuring content of 2, 4-epibrassinolide in dendrobium officinale | |
Hou et al. | Development of a method to screen and isolate bioactive constituents from Stellera chamaejasme by ultrafiltration and liquid chromatography combined with semi‐preparative high‐performance liquid chromatography and high‐speed counter current chromatography | |
CN108802230B (en) | Method for detecting tanshinol and metabolite thereof in biological sample | |
CN106226426A (en) | A kind of high performance liquid chromatography splits the method for canagliflozin five-membered ring impurity enantiomer | |
CN107703235B (en) | Supercritical fluid chromatographic separation method for lenalidomide enantiomer | |
CN113533548B (en) | Method for detecting 1-vinyl imidazole in chemical product | |
Zhao et al. | pH‐Zone‐refining counter‐current chromatography for two new lipo‐alkaloids separated from refined alkaline extraction of Kusnezoff monkshood root | |
Ren et al. | Prostate cell membrane chromatography–LC/MS method for screening α 1A-adrenoceptor antagonists from Lotus plumule | |
CN116642970A (en) | Sample pretreatment method for simultaneously detecting 6 drug concentrations in blood | |
Zhou et al. | Analysis of lignans in Magnoliae Flos by turbulent flow chromatography with online solid‐phase extraction and high‐performance liquid chromatography with tandem mass spectrometry | |
CN110824088B (en) | Method for determining content of suplatast tosilate in plasma by using HPLC-MS (high Performance liquid chromatography-Mass Spectrometry) | |
CN111721873A (en) | Method for separating dihydromyricetin and (2S,3S) chiral isomer thereof based on reversed-phase HPLC | |
CN113759048A (en) | Inspection method of mono-tert-butyl octadecanedioate | |
CN108362789B (en) | High performance liquid chromatography detection method for abamectin sodium optical isomer | |
CN111721874A (en) | HPLC method for separating tadalafil and chiral isomer thereof | |
CN1766605A (en) | Chromatography for simultaneous detection of four constituents in hydrogen-peroxide working solution | |
CN111024868B (en) | Method for detecting content of alpha-high nojirimycin in white tree medicinal material | |
CN113917027B (en) | Optical isomer separation detection method of avanafil and intermediate thereof | |
CN111735899B (en) | Analysis method of naphthalene ring containing substituent |
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 |