CN111220727A - Method for detecting enantiomer in ivabradine hydrochloride intermediate and application - Google Patents
Method for detecting enantiomer in ivabradine hydrochloride intermediate and application Download PDFInfo
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- CN111220727A CN111220727A CN202010051898.0A CN202010051898A CN111220727A CN 111220727 A CN111220727 A CN 111220727A CN 202010051898 A CN202010051898 A CN 202010051898A CN 111220727 A CN111220727 A CN 111220727A
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- ivabradine hydrochloride
- enantiomer
- hydrochloride intermediate
- mobile phase
- solution
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- HLUKNZUABFFNQS-ZMBIFBSDSA-N ivabradine hydrochloride Chemical compound Cl.C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 HLUKNZUABFFNQS-ZMBIFBSDSA-N 0.000 title claims abstract description 87
- 229960000504 ivabradine hydrochloride Drugs 0.000 title claims abstract description 81
- 238000000034 method Methods 0.000 title claims abstract description 36
- 238000001514 detection method Methods 0.000 claims abstract description 68
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract description 30
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims abstract description 14
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012488 sample solution Substances 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 5
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- WLTIOQZDUHPQMO-IJHRGXPZSA-N CN(CCCC1C=CC2=CC=CC=C2NC1=O)C[C@@H]3CC4=CC(=C(C=C34)OC)OC Chemical compound CN(CCCC1C=CC2=CC=CC=C2NC1=O)C[C@@H]3CC4=CC(=C(C=C34)OC)OC WLTIOQZDUHPQMO-IJHRGXPZSA-N 0.000 claims description 37
- 239000000523 sample Substances 0.000 claims description 34
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 26
- WLTIOQZDUHPQMO-ROPPNANJSA-N CN(CCCC1C=CC2=CC=CC=C2NC1=O)C[C@H]3CC4=CC(=C(C=C34)OC)OC Chemical group CN(CCCC1C=CC2=CC=CC=C2NC1=O)C[C@H]3CC4=CC(=C(C=C34)OC)OC WLTIOQZDUHPQMO-ROPPNANJSA-N 0.000 claims description 25
- 238000005259 measurement Methods 0.000 claims description 23
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- 239000000945 filler Substances 0.000 claims description 8
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- 238000012360 testing method Methods 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 238000007865 diluting Methods 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
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- 229920002678 cellulose Polymers 0.000 claims description 4
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- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 abstract description 5
- 238000004445 quantitative analysis Methods 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
- 229960003825 ivabradine Drugs 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- -1 3-chloropropyl Chemical group 0.000 description 2
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- SAVVFXUMMFHSJC-UHFFFAOYSA-N 1-(3,4-dimethoxy-7-bicyclo[4.2.0]octa-1,3,5-trienyl)-n-methylmethanamine Chemical compound COC1=C(OC)C=C2C(CNC)CC2=C1 SAVVFXUMMFHSJC-UHFFFAOYSA-N 0.000 description 1
- SAVVFXUMMFHSJC-SECBINFHSA-N 1-[(7s)-3,4-dimethoxy-7-bicyclo[4.2.0]octa-1,3,5-trienyl]-n-methylmethanamine Chemical compound COC1=C(OC)C=C2[C@@H](CNC)CC2=C1 SAVVFXUMMFHSJC-SECBINFHSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
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- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 1
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 1
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- 238000007796 conventional method Methods 0.000 description 1
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- 238000009826 distribution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000020937 fasting conditions Nutrition 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
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- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 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
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
- G01N30/8679—Target compound analysis, i.e. whereby a limited number of peaks is analysed
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N2030/042—Standards
- G01N2030/047—Standards external
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- 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)
- Engineering & Computer Science (AREA)
- Library & Information Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
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CN202010051898.0A CN111220727B (en) | 2020-01-17 | 2020-01-17 | Method for detecting enantiomer in ivabradine hydrochloride intermediate and application |
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CN202010051898.0A CN111220727B (en) | 2020-01-17 | 2020-01-17 | Method for detecting enantiomer in ivabradine hydrochloride intermediate and application |
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CN111220727A true CN111220727A (en) | 2020-06-02 |
CN111220727B CN111220727B (en) | 2022-04-26 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114324714A (en) * | 2021-01-05 | 2022-04-12 | 海南鑫开源医药科技有限公司 | Method for detecting (1S) -4, 5-dimethoxy-1- [ (methylamino) methyl ] benzocyclobutane hydrochloride |
CN114778745A (en) * | 2022-06-21 | 2022-07-22 | 南京威凯尔生物医药科技有限公司 | Method for detecting Luneburgen intermediate and enantiomer impurities thereof by high performance liquid chromatography |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101609071A (en) * | 2008-06-16 | 2009-12-23 | 北京德众万全药物技术开发有限公司 | A kind of HPLC method analysis separates the method for ivabradine hydrochloride intermediate optical isomer |
CN103884783A (en) * | 2013-08-02 | 2014-06-25 | 山东新时代药业有限公司 | Method for analyzing and detecting ivabradine intermediate |
WO2014102827A1 (en) * | 2012-12-28 | 2014-07-03 | Glenmark Pharmaceuticals Limited; Glenmark Generics Limited | Process for preparation of ivabradine |
CN104447554A (en) * | 2013-09-22 | 2015-03-25 | 广东众生药业股份有限公司 | Preparation method for ivabradine and hydrochloride thereof |
-
2020
- 2020-01-17 CN CN202010051898.0A patent/CN111220727B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101609071A (en) * | 2008-06-16 | 2009-12-23 | 北京德众万全药物技术开发有限公司 | A kind of HPLC method analysis separates the method for ivabradine hydrochloride intermediate optical isomer |
WO2014102827A1 (en) * | 2012-12-28 | 2014-07-03 | Glenmark Pharmaceuticals Limited; Glenmark Generics Limited | Process for preparation of ivabradine |
CN103884783A (en) * | 2013-08-02 | 2014-06-25 | 山东新时代药业有限公司 | Method for analyzing and detecting ivabradine intermediate |
CN104447554A (en) * | 2013-09-22 | 2015-03-25 | 广东众生药业股份有限公司 | Preparation method for ivabradine and hydrochloride thereof |
Non-Patent Citations (3)
Title |
---|
MODEELEK FERENCZ 等: "Simultaneous determination of chiral and achiral impurities of ivabradine on a cellulose tris(3-chloro-4-methylphenylcarbamate) chiral column using polar organic mode", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
杨晓莉 等: "HPLC法测定盐酸伊伐布雷定及其片剂中有关物质", 《中国药事》 * |
赵爱慧 等: "盐酸伊伐布雷定有关物质的分离、结构鉴定及合成", 《中国医药工业杂志》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114324714A (en) * | 2021-01-05 | 2022-04-12 | 海南鑫开源医药科技有限公司 | Method for detecting (1S) -4, 5-dimethoxy-1- [ (methylamino) methyl ] benzocyclobutane hydrochloride |
CN114324714B (en) * | 2021-01-05 | 2023-06-30 | 海南鑫开源医药科技有限公司 | Method for detecting (1S) -4, 5-dimethoxy-1- [ (methylamino) methyl ] benzocyclobutane hydrochloride |
CN114778745A (en) * | 2022-06-21 | 2022-07-22 | 南京威凯尔生物医药科技有限公司 | Method for detecting Luneburgen intermediate and enantiomer impurities thereof by high performance liquid chromatography |
CN114778745B (en) * | 2022-06-21 | 2022-09-16 | 南京威凯尔生物医药科技有限公司 | Method for detecting Lobrazil intermediate and enantiomer impurities thereof by high performance liquid chromatography |
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Effective date of registration: 20220512 Address after: 570311 Building 1, 8 Yaogu erheng Road, Xiuying District, Haikou City, Hainan Province Patentee after: Hainan xinkaiyuan Pharmaceutical Technology Co.,Ltd. Address before: 570100 No.8, erheng Road, Yaogu, Xiuying District, Haikou City, Hainan Province Patentee before: Beijing Xin Kai Yuan Pharmaceutical Technology Co.,Ltd. Hainan branch |
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Denomination of invention: Detection method and application of enantiomers in intermediate of ivabradine hydrochloride Effective date of registration: 20220629 Granted publication date: 20220426 Pledgee: Huaxia Bank Co.,Ltd. Haikou Branch Pledgor: Hainan xinkaiyuan Pharmaceutical Technology Co.,Ltd. Registration number: Y2022980009495 |
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Date of cancellation: 20231116 Granted publication date: 20220426 Pledgee: Huaxia Bank Co.,Ltd. Haikou Branch Pledgor: Hainan xinkaiyuan Pharmaceutical Technology Co.,Ltd. Registration number: Y2022980009495 |
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Denomination of invention: Detection method and application of enantiomers in intermediate of Ivabradine hydrochloride Effective date of registration: 20231122 Granted publication date: 20220426 Pledgee: Huaxia Bank Co.,Ltd. Haikou Branch Pledgor: Hainan xinkaiyuan Pharmaceutical Technology Co.,Ltd. Registration number: Y2023980067130 |
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