CN113866337B - Mass analysis method for separating and measuring oseltamivir phosphate isomer - Google Patents
Mass analysis method for separating and measuring oseltamivir phosphate isomer Download PDFInfo
- Publication number
- CN113866337B CN113866337B CN202111240912.2A CN202111240912A CN113866337B CN 113866337 B CN113866337 B CN 113866337B CN 202111240912 A CN202111240912 A CN 202111240912A CN 113866337 B CN113866337 B CN 113866337B
- Authority
- CN
- China
- Prior art keywords
- solution
- oseltamivir phosphate
- measuring
- sample
- separating
- 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
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical class CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 title claims abstract description 60
- 238000004458 analytical method Methods 0.000 title claims abstract description 22
- 239000012535 impurity Substances 0.000 claims abstract description 38
- 229960002194 oseltamivir phosphate Drugs 0.000 claims abstract description 28
- 239000012488 sample solution Substances 0.000 claims abstract description 20
- 238000001514 detection method Methods 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 43
- 239000013558 reference substance Substances 0.000 claims description 21
- 239000000523 sample Substances 0.000 claims description 18
- 239000000706 filtrate Substances 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000011550 stock solution Substances 0.000 claims description 10
- 239000012088 reference solution Substances 0.000 claims description 9
- 238000005303 weighing Methods 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- KBRZBBOTZJFKFH-UHFFFAOYSA-N (3,5-dichlorophenyl) carbamate Chemical compound NC(=O)OC1=CC(Cl)=CC(Cl)=C1 KBRZBBOTZJFKFH-UHFFFAOYSA-N 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000007983 Tris buffer Substances 0.000 claims description 5
- 238000007865 diluting Methods 0.000 claims description 5
- 239000000741 silica gel Substances 0.000 claims description 5
- 229910002027 silica gel Inorganic materials 0.000 claims description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000004949 mass spectrometry Methods 0.000 claims 2
- 239000000126 substance Substances 0.000 abstract description 5
- 229960003752 oseltamivir Drugs 0.000 description 9
- 230000035945 sensitivity Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- NENPYTRHICXVCS-YNEHKIRRSA-N oseltamivir acid Chemical compound CCC(CC)O[C@@H]1C=C(C(O)=O)C[C@H](N)[C@H]1NC(C)=O NENPYTRHICXVCS-YNEHKIRRSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 208000037797 influenza A Diseases 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- -1 ethanol-methanol-trifluoroacetic acid-diethylamine Chemical compound 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 208000037798 influenza B Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
-
- 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
- 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)
- Investigating Or Analysing Biological Materials (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a mass analysis method for separating and measuring oseltamivir phosphate isomer, relates to the technical field of mass analysis, and aims to solve the problem that an existing oseltamivir phosphate related substance detection method cannot effectively separate isomers. The invention prepares a sample solution, a control solution and an impurity control solution, oseltamivir phosphate isomer RSS, SRR, SSS, RRR, SSR and SRS, and adopts a high performance liquid chromatograph for detection. The oseltamivir phosphate isomer can be precisely separated. The invention is applied to the field of mass analysis.
Description
Technical Field
The invention relates to the technical field of mass analysis, in particular to a mass analysis method for separating and measuring oseltamivir phosphate isomers.
Background
Oseltamivir phosphate (seltamivirphospate), chemical name: (r, 4r,5 s) 4-acetamide-5-amino-3 (-propoxyethyl) 1-cyclohexane-1 carboxylic acid ethyl ester phosphate. Oseltamivir phosphate is an antiviral agent, and is mainly used for preventing or treating influenza A and B viruses. Has obvious anti-influenza A virus effect on adults and children over 1 year old.
Oseltamivir phosphate may produce impurities I, II, III and isomers during preparation and synthesis. Wherein the impurities I, II and III are degradation impurities, and the impurities I, II and III are determined by high performance liquid chromatography in the 2020 edition of the current Chinese pharmacopoeia. The oseltamivir phosphate isomer has no quality control requirement and no related detection method. Therefore, the separation and measurement of oseltamivir phosphate and isomers are very important for quality control of oseltamivir phosphate. Oseltamivir phosphate is used as a common drug for treating influenza, is frequently used in daily life, and a mass analysis method for separating and measuring oseltamivir phosphate isomers is developed for ensuring the drug quality and production research.
Disclosure of Invention
The invention aims to provide a mass analysis method for separating and measuring oseltamivir phosphate isomer, which aims to solve the problem that the existing oseltamivir phosphate related substance detection method cannot effectively separate the isomer.
The invention discloses a mass analysis method for separating and measuring oseltamivir phosphate isomer, which comprises the following steps:
step one, preparing a sample solution:
the sample solution contains oseltamivir phosphate 1-3 mg/mL; the preparation method comprises the following steps: precisely weighing a sample, placing the sample in a measuring flask, and quantitatively diluting the sample with a mobile phase to a scale; shaking, filtering, and taking the subsequent filtrate as a sample solution;
step two, preparing a control solution:
the control solution contains oseltamivir phosphate of 1-3 mug/mL; the preparation method comprises the following steps: taking the prepared sample solution, placing the sample solution into a measuring flask, and adding a mobile phase to dilute to a scale; precisely measuring the solution, placing in a measuring flask, adding mobile phase to dilute to scale, shaking, filtering, and collecting filtrate as control solution;
step three, impurity reference substance solution:
the impurity reference substance solution contains 15-25 mug/mL of impurity reference substance; the preparation method comprises the following steps: respectively taking oseltamivir phosphate isomer RSS, SRR, SSS, RRR, SSR and SRS, precisely weighing, respectively placing in a measuring flask, adding a mobile phase, quantitatively diluting to scale, and taking the mixed solution as a stock solution of each impurity reference substance; precisely measuring each impurity stock solution, placing the stock solution in a volumetric flask, and adding a mobile phase to dilute to a scale; shaking, filtering, and collecting the filtrate as impurity reference solution;
step four, sample analysis: and detecting by adopting a high performance liquid chromatograph according to the following conditions:
a silica gel surface is covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) or a chromatographic column with equivalent efficiency; n-hexane-absolute ethyl alcohol-methanol-trifluoroacetic acid-diethylamine with a volume ratio of 900:60:40:4:2 is used as a mobile phase; the detection wavelength is 240nm; column temperature is 35 ℃; the flow rate is 1.0mL/min; running for 60min; sample injection volume 25. Mu.L; controlling the temperature of the sample bin to be 4 ℃;
and carrying out mass analysis on chromatographic peaks of the obtained impurity reference substance solution, the reference solution and the sample solution, thereby completing the mass analysis method for separating and measuring oseltamivir phosphate isomers.
Further, the concentration of the impurity reference substance solution is 20 mug/mL.
Further, the oseltamivir phosphate is 2 mug/mL.
Further, the oseltamivir phosphate is 2mg/mL.
Further, the n-hexane, absolute ethanol, methanol, trifluoroacetic acid and diethylamine are all chromatographic pure.
Further, cellulose-tris (3, 5-dichlorophenyl carbamate) or a chromatographic column with equivalent performance is covalently bonded on the surface of the silica gel, and the specification of the chromatographic column is 4.6x150 mm and 3um.
The invention has the following beneficial effects:
the invention considers that oseltamivir phosphate has a plurality of isomers, and the oseltamivir phosphate related substances in the 2020 edition of Chinese pharmacopoeia are detected by a reverse C8 chromatographic column by high performance liquid chromatography, and isomer peaks are overlapped and cannot be separated. In the form of six isomers of oseltamivir phosphate (RSR): the oseltamivir phosphate isomer can be accurately separated by selecting high performance liquid chromatography forward chromatographic column detection based on oseltamivir Wei Fei enantiomer II (SRS), oseltamivir hydrochloride (SSR), oseltamivir impurity (SSS), oseltamivir impurity 17 (RRR), oseltamivir impurity (RSS) and Oseltamivir impurity 47 (SRR) to prepare a sample, a reference substance and an impurity reference substance.
Drawings
Fig. 1 is a liquid chromatogram of example 1.
Detailed Description
For further explanation of the technical scheme of the present invention, specific test data and the accompanying tables will be described in detail.
The mass analysis method for separating and measuring oseltamivir phosphate isomer comprises the following specific steps:
1. impurity control solution, control solution and test solution of the invention:
and detecting the impurity reference substance solution, the reference solution and the test sample solution by high performance liquid chromatography. Detection conditions: a silica gel surface is covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) or a chromatographic column with equivalent efficiency; n-hexane-absolute ethanol-methanol-trifluoroacetic acid-diethylamine (900:60:40:4:2) as mobile phase; the detection wavelength is 240nm; column temperature is 35 ℃; the flow rate is 1.0mL/min; running for 60min; sample volume 25. Mu.l; the temperature of the sample bin is controlled to be 4 ℃. And carrying out mass analysis on chromatographic peaks of the impurity reference substance solution, the reference solution and the test substance solution.
The impurity reference substance solution is 20 mug/mL of impurity reference substance, and the specific preparation method is as follows: respectively taking 5.0mg of oseltamivir phosphate isomer (RSS), (SRR), (SSS), (RRR), (SSR) and (SRS), precisely weighing, respectively placing into 25mL measuring bottles, adding mobile phase, quantitatively diluting to scale, and taking as stock solution of each impurity reference substance; precisely measuring 1.0mL of each impurity stock solution, placing the stock solution into a 10mL volumetric flask, and adding a mobile phase to dilute to a scale; shaking, filtering, and collecting filtrate as impurity reference solution.
The sample solution contains oseltamivir phosphate 2mg/mL, and the specific preparation method is as follows: weighing 500mg of a sample to be tested precisely, placing the sample into a 10mL measuring flask, and adding a mobile phase for quantitative dilution to a scale; shaking, filtering, and taking the subsequent filtrate as a sample solution.
The control solution contains oseltamivir phosphate of 2 mug/mL, and the specific preparation method is as follows: taking 1.0mL of the sample solution, placing the sample solution into a 100mL measuring flask, and adding a mobile phase to dilute to a scale; precisely measuring 1.0mL of the solution, placing a 10mL measuring flask, adding a mobile phase for dilution to a scale, shaking uniformly, filtering, and taking a subsequent filtrate as a control solution.
2. System applicability solution
1. Solution a: oseltamivir hydrochloride (SSR) is taken, 5.0mg is precisely weighed, placed in a 25mL volumetric flask, dissolved by a mobile phase and fixed to a scale, and used as an isomer stock solution.
2. Solution B: taking oseltamivir phosphate reference substance, precisely weighing 20mg, placing in a 10mL measuring flask, dissolving with 3-4mL of mobile phase, precisely weighing 1.0mL of solution A, placing in the 10mL measuring flask, metering the volume to scale with the mobile phase, shaking uniformly, filtering, and taking the subsequent filtrate as a resolution solution.
3. System applicability solution oseltamivir phosphate 1mg/mL: taking oseltamivir phosphate as a reference substance, precisely weighing 10mg, placing in a 10mL measuring flask, fixing the volume to a scale by using a mobile phase, shaking uniformly, filtering, and taking a subsequent filtrate as a system applicability solution.
3. System applicability requirement
Oseltamivir hydrochloride (SSR) should have a degree of separation from oseltamivir phosphate of not less than 1.5.
The system applicability solution is continuously injected for 5 times, and the area RSD of the oseltamium phosphate Wei Feng is not more than 10.0 percent.
4. The sensitivity solution contained oseltamivir phosphate 2 μg/mL: precisely measuring 1.0mL of the two-system applicability solution item 3, placing the two-system applicability solution item in a 50mL measuring flask, and fixing the volume to the scale; precisely measuring 1.0mL of the solution, placing a 10mL measuring flask, fixing the volume to a scale, shaking uniformly, filtering, and taking the subsequent filtrate as a sensitivity solution.
5. Sensitivity requirements: the sensitivity solution S/N should be greater than 10.
6. Taking a system applicability solution, a separation degree solution, a sensitivity solution, a reference substance solution, a reference solution and a test sample solution, respectively injecting into a liquid chromatograph, and recording a chromatogram.
7. And (3) calculating results: self-control method using oseltamivir phosphate as main component.
The results are shown in FIG. 1 and Table 1.
TABLE 1
Sample name | Retention time | Relative retention time |
Oseltamivir hydrochloride (SSR) | 6.805 | 0.84 |
Oseltamivir phosphate (RSR) | 8.117 | 1.00 |
Oseltamivir impurity 46(SSS) | 8.902 | 1.10 |
Oseltamivir impurity 17(RRR) | 9.307 | 1.15 |
Oseltamium Wei Fei enantiomer II (SRS) | 10.079 | 1.24 |
Oseltamivir impurity 20(RSS) | 11.322 | 1.39 |
Oseltamivir impurity 47(SRR) | 11.806 | 1.45 |
The above-mentioned experimental data are actual experimental result data of the present invention, and the experimental data cannot be used for limiting the scope of the present invention, and all the improvements and modifications made on the principles and methods of the present invention are considered to be within the scope of the present invention.
Claims (6)
1. A mass analysis method for separating and measuring oseltamivir phosphate isomer, which is characterized by comprising the following steps:
step one, preparing a sample solution:
the sample solution contains oseltamivir phosphate 1-3 mg/mL; the preparation method comprises the following steps: precisely weighing a sample, placing the sample in a measuring flask, and quantitatively diluting the sample with a mobile phase to a scale; shaking, filtering, and taking the subsequent filtrate as a sample solution;
step two, preparing a control solution:
the control solution contains oseltamivir phosphate of 1-3 mug/mL; the preparation method comprises the following steps: taking the prepared sample solution, placing the sample solution into a measuring flask, and adding a mobile phase to dilute to a scale; precisely measuring the solution, placing in a measuring flask, adding mobile phase to dilute to scale, shaking, filtering, and collecting filtrate as control solution;
step three, impurity reference substance solution:
the impurity reference substance solution contains 15-25 mug/mL of impurity reference substance; the preparation method comprises the following steps: respectively taking oseltamivir phosphate isomer RSS, SRR, SSS, RRR, SSR and SRS, precisely weighing, respectively placing in a measuring flask, adding a mobile phase, quantitatively diluting to scale, and taking the mixed solution as a stock solution of each impurity reference substance; precisely measuring each impurity stock solution, placing the stock solution in a volumetric flask, and adding a mobile phase to dilute to a scale; shaking, filtering, and collecting the filtrate as impurity reference solution;
step four, sample analysis: and detecting by adopting a high performance liquid chromatograph according to the following conditions:
a silica gel surface is covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) or a chromatographic column with equivalent efficiency; n-hexane-absolute ethyl alcohol-methanol-trifluoroacetic acid-diethylamine with a volume ratio of 900:60:40:4:2 is used as a mobile phase; the detection wavelength is 240nm; column temperature is 35 ℃; the flow rate is 1.0mL/min; running for 60min; sample injection volume 25. Mu.L; controlling the temperature of the sample bin to be 4 ℃;
and carrying out mass analysis on chromatographic peaks of the obtained impurity reference substance solution, the reference solution and the sample solution, thereby completing the mass analysis method for separating and measuring oseltamivir phosphate isomers.
2. The mass analysis method for separating and measuring oseltamivir phosphate isomer according to claim 1, wherein the concentration of the impurity reference solution is 20 μg/mL.
3. The mass analysis method for separating and measuring oseltamivir phosphate isomer according to claim 1, wherein the sample solution contains oseltamivir phosphate 2 μg/mL.
4. The mass analysis method for separating and measuring oseltamivir phosphate isomer according to claim 1, wherein the control solution contains oseltamivir phosphate 2mg/mL.
5. The mass spectrometry method for separating and determining oseltamivir phosphate isomer according to claim 1, wherein n-hexane, absolute ethanol, methanol, trifluoroacetic acid and diethylamine are all chromatographically pure.
6. The mass spectrometry method for separating and determining oseltamivir phosphate isomer according to claim 1, wherein the silica gel surface is covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) or equivalent performance chromatographic column with specification of 4.6 x 150mm, 3um.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111240912.2A CN113866337B (en) | 2021-10-25 | 2021-10-25 | Mass analysis method for separating and measuring oseltamivir phosphate isomer |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111240912.2A CN113866337B (en) | 2021-10-25 | 2021-10-25 | Mass analysis method for separating and measuring oseltamivir phosphate isomer |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113866337A CN113866337A (en) | 2021-12-31 |
CN113866337B true CN113866337B (en) | 2024-03-08 |
Family
ID=78997862
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111240912.2A Active CN113866337B (en) | 2021-10-25 | 2021-10-25 | Mass analysis method for separating and measuring oseltamivir phosphate isomer |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113866337B (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115326999B (en) * | 2022-10-12 | 2022-12-27 | 深圳市海滨制药有限公司 | Detection method of oseltamivir epoxy intermediate and isomer thereof |
CN117214369B (en) * | 2023-11-09 | 2024-02-02 | 山东百诺医药股份有限公司 | Liquid chromatography method for detecting related substances of oseltamium phosphate Wei Ganhun suspension |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108047076A (en) * | 2017-12-26 | 2018-05-18 | 杭州新博思生物医药有限公司 | A kind of preparation method of Oseltamivir enantiomter |
CN108047077A (en) * | 2017-12-27 | 2018-05-18 | 杭州新博思生物医药有限公司 | A kind of preparation method of Oseltamivir chiral impurity |
CN109580850A (en) * | 2019-01-29 | 2019-04-05 | 杭州新博思生物医药有限公司 | A kind of efficient liquid-phase chromatography method of separation and measurement Oseltamivir phosphate and its specific impurities |
CN109870521A (en) * | 2019-04-03 | 2019-06-11 | 杭州新博思生物医药有限公司 | A kind of method of normal phase chromatography separation Oseltamivir phosphate enantiomter |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102046592B (en) * | 2008-05-30 | 2014-12-10 | 住友化学株式会社 | Process for producing oseltamivir phosphate and intermediate compound |
-
2021
- 2021-10-25 CN CN202111240912.2A patent/CN113866337B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108047076A (en) * | 2017-12-26 | 2018-05-18 | 杭州新博思生物医药有限公司 | A kind of preparation method of Oseltamivir enantiomter |
CN108047077A (en) * | 2017-12-27 | 2018-05-18 | 杭州新博思生物医药有限公司 | A kind of preparation method of Oseltamivir chiral impurity |
CN109580850A (en) * | 2019-01-29 | 2019-04-05 | 杭州新博思生物医药有限公司 | A kind of efficient liquid-phase chromatography method of separation and measurement Oseltamivir phosphate and its specific impurities |
CN109870521A (en) * | 2019-04-03 | 2019-06-11 | 杭州新博思生物医药有限公司 | A kind of method of normal phase chromatography separation Oseltamivir phosphate enantiomter |
Also Published As
Publication number | Publication date |
---|---|
CN113866337A (en) | 2021-12-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113866337B (en) | Mass analysis method for separating and measuring oseltamivir phosphate isomer | |
CN112903838A (en) | Method for determining related substances in Favilavir | |
CN115097023A (en) | High performance liquid chromatography detection method for zolmitamine related substances | |
CN109387587B (en) | Detection method of L-2-amino-5-guanidino valeric acid enantiomer | |
CN113049687B (en) | Method for detecting ambroxol hydrochloride raw material and injection related substances | |
CN111721858B (en) | Method for determining genotoxic impurities in rivaroxaban | |
CN113702514A (en) | Method for determining atorvastatin calcium related impurity I | |
CN114689737B (en) | Analysis method of S-o-chlorophenylglycine methyl tartrate related substances | |
CN110208419B (en) | Method for detecting impurities in bivalirudin | |
CN112881538B (en) | Method for detecting impurities and enantiomers in fudosteine and fudosteine tablets | |
CN115032284A (en) | Method for separating and detecting related substances in chewable tablets | |
CN112611813A (en) | Method for testing genotoxic impurities of Sacubitril valsartan sodium starting material | |
CN115453014B (en) | Detection method of butylphthalide and related substances thereof | |
CN116124926B (en) | Method for determining content of 2-mercaptopyridine in plasmid | |
CN114740119B (en) | Method for detecting 11 components in compound amino acid injection | |
CN116593606B (en) | Method for separating and detecting related substances of lacosamide intermediate | |
CN115469039B (en) | Butylphthalide and detection method of related substances thereof | |
CN114200050B (en) | HPLC detection method for content of related substances in p-bromoanisole | |
CN117310022B (en) | Method for separating and detecting related substances of quinuclidine benzhydrol as intermediate of ubenimex | |
CN111380991B (en) | Method for detecting content of degradation impurities in vitamin C medicament | |
CN110850012B (en) | Detection method of 1- (2, 3-dichlorophenyl) piperazine hydrochloride and related substances thereof | |
CN115236255A (en) | Method for detecting loxoprofen sodium related substances | |
CN118191132A (en) | Analysis method for detecting impurities including nitrosamine in levosalbutamol hydrochloride | |
CN118225924A (en) | Etomidate starting material and separation detection method of enantiomer thereof | |
CN114428141A (en) | Method for detecting content of free hydrazine impurities in isoniazid |
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 |