CN105085481A - Recrystallization method of rabeprazole sodium - Google Patents
Recrystallization method of rabeprazole sodium Download PDFInfo
- Publication number
- CN105085481A CN105085481A CN201410211916.1A CN201410211916A CN105085481A CN 105085481 A CN105085481 A CN 105085481A CN 201410211916 A CN201410211916 A CN 201410211916A CN 105085481 A CN105085481 A CN 105085481A
- Authority
- CN
- China
- Prior art keywords
- organic solvent
- ketone
- sodium rabeprazole
- sodium
- rabeprazole
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention belongs to the field of pharmaceutical chemistry and specifically relates to a recrystallization method of rabeprazole sodium. A mixed solvent of a ketone organic solvent and a cyclic ether organic solvent is used for crystallization, wherein the ketone organic solvent is preferably selected from acetone, methyl ethyl ketone and cyclohexanone; and the cyclic ether organic solvent is preferably selected from tetrahydrofuran and 1,4-dioxane. The rabeprazole sodium prepared according to the method has high purity, contains less impurities and accords with crude drug standards.
Description
Technical field
The invention belongs to medicinal chemistry art, be specifically related to a kind of recrystallization method of Sodium rabeprazole.
Background technology
Sodium rabeprazole (SodiumReheprazole) is s-generation proton pump inhibitor, and it is by suppressing the effect of H+/K+-ATP enzyme system and gastric acid secretion inhibiting specifically.It is benzoglyoxaline proton pump inhibitor up-to-date after omeprazole, lansoprazole.Be applicable to treatment peptide ulceration clinically as stomach ulcer, duodenal ulcer etc., reflux esophagitis and gastrinoma.Sodium rabeprazole is researched and developed by Japanese Wei Cai company, and in 1997 in Japan's listing, formulation is enteric coated tablet.21 country's listings in the whole world at present, Chinese Ye Youduo company produces sodium rabeprazole enteric-coated, enteric coated capsule two kinds of formulations.Sodium rebeilazole for injection use is that Cadila pharmaceutical Co. Ltd of India ratifies listing in May, 2004 first in India, and specification is 20mg.Sodium rabeprazole has now become the leading product of proton pump inhibitor.
The chemistry of Sodium rabeprazole is called: 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridyl] methyl] sulfinyl]-1H – benzoglyoxaline sodium salt, molecular formula: C
18h
20n
3naO
3s, structural formula is as follows:
The common adverse reactions of Sodium rabeprazole is headache, other rare untoward reaction myasthenia, constipation, dizziness, feel sick, stomachache and urine abnormal, may be caused by impurity wherein.Starting raw material in Sodium rabeprazole building-up process, intermediate, end product analogue and degraded product etc. all may become its impurity, thus affect the quality of product.Therefore, it is very necessary for refining bulk drug, improving its purity.
Sodium rabeprazole synthetic method report is more, such as patent documentation CN102952119A, CN102219777A, CN102993179, but but rarely has report about the method for its recrystallization.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of recrystallization method of Sodium rabeprazole, to obtain the high bulk drug Sodium rabeprazole of purity.
A recrystallization method for Sodium rabeprazole, adopts the mixed solvent of organic solvent of ketone and ring ether organic solvent to carry out recrystallization.
Described organic solvent of ketone is selected from one or more in acetone, methylethylketone, pimelinketone, espeleton, mibk, preferred acetone, methylethylketone, pimelinketone.
Described ring ether organic solvent be selected from tetrahydrofuran (THF) or 1, one or both in 4-dioxane.
Sodium rabeprazole recrystallization method provided by the invention, specifically comprise the following steps: in a heated condition, by Sodium rabeprazole dissolving crude product in the mixed solvent of organic solvent of ketone and ring ether organic solvent, adopt the method for cooling to make Sodium rabeprazole crystallization, filter and obtain Sodium rabeprazole crystallization.The preferred Temperature fall of cooling method; The volume ratio of organic solvent of ketone and ring ether organic solvent is 3:1 ~ 8:1, preferred 4:1 ~ 6:1, more preferably 5:1.
Beneficial effect of the present invention: the bulk drug Sodium rabeprazole purity obtained according to technical solution of the present invention is high, foreign matter content is very low.
Embodiment
Further illustrate the present invention below by specific embodiment, but the present invention is not limited to these embodiments, it should be understood that embodiments of the invention are for illustration of the present invention instead of limitation of the present invention.The simple modifications that essence according to the present invention is carried out for the present invention all belongs to the scope of protection of present invention.
Sodium rabeprazole crude product of the present invention is purchased from Changzhou Kangli Pharmaceutical Co., Ltd.
The foreign matter content of the embodiment of the present invention adopts following methods to detect:
Get this product appropriate, add 0.001mol/L sodium hydroxide solution to make in every 1mL about containing the solution of 0.5mg Sodium rabeprazole as need testing solution; It is appropriate that precision measures reference substance, adds 0.001mol/L sodium hydroxide solution and make in every 1mL containing 5 μ g solution solution in contrast.Be weighting agent with octadecylsilane chemically bonded silica; Be moving phase with phosphate buffered saline buffer (get Sodium phosphate dibasic 1.119g and SODIUM PHOSPHATE, MONOBASIC 0.179g, the 1000mL that adds water dissolves, mixing)-acetonitrile (60:40); Determined wavelength is 286nm.Number of theoretical plate calculates should be not less than 2000 by rabeprazole peak.Get contrast solution 20 μ l injection liquid chromatography, regulate monitoring sensitivity, make the peak height of principal constituent chromatographic peak be about 20% of full range.Get need testing solution and each 20 μ L of contrast solution again, respectively injection liquid chromatography, record color atlas is to 2 times of main peak retention time.If any impurity peaks in the color atlas of need testing solution, measure each impurity peak area and, 1.0 times of contrast solution main peak area must not be greater than.
Reference example 1
Sodium rabeprazole crude product 10g is added in 500mL eggplant-shape bottle, under heating condition, adds acetone until crude product all dissolves.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 8.1g Sodium rabeprazole, HPLC analyzes, foreign matter content 0.8%.
Reference example 2
Just Sodium rabeprazole crude product 10g adds in 500mL eggplant-shape bottle, adds pimelinketone until crude product all dissolves under heating condition.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 8.3g Sodium rabeprazole, HPLC analyzes, foreign matter content 1.2%.Embodiment 1
Sodium rabeprazole crude product 10g is added in 500mL eggplant-shape bottle, adds acetone-tetrahydrofuran (THF) (3:1) mixed solvent under heating condition until crude product all dissolves.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 8.5g Sodium rabeprazole, HPLC analyzes, and foreign matter content is 0.4%.
Embodiment 2
Just Sodium rabeprazole crude product 10g adds in 500mL eggplant-shape bottle, adds acetone-Isosorbide-5-Nitrae-dioxane (3:1) mixed solvent until crude product all dissolves under heating condition.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 8.3g Sodium rabeprazole, HPLC analyzes, and foreign matter content is 0.28%.
Embodiment 3
Sodium rabeprazole crude product 10g is added in 500mL eggplant-shape bottle, adds acetone-tetrahydrofuran (THF) (5:1) mixed solvent under heating condition until crude product all dissolves.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 8.1g Sodium rabeprazole, HPLC analyzes, and foreign matter content is 0.21%.
Embodiment 4
Sodium rabeprazole crude product 10g is added in 500mL eggplant-shape bottle, adds pimelinketone-tetrahydrofuran (THF) (8:1) mixed solvent under heating condition until crude product all dissolves.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 7.8g Sodium rabeprazole, HPLC analyzes, and foreign matter content is 0.30%.
Embodiment 5
Sodium rabeprazole crude product 10g is added in 500mL eggplant-shape bottle, adds butanone-tetrahydrofuran (THF) (5:1) mixed solvent under heating condition until crude product all dissolves.Stop heating, leave standstill crystallization, spend the night.Filter, obtain 8.2g Sodium rabeprazole, HPLC analyzes, and foreign matter content is 0.20%.
Claims (7)
1. a Sodium rabeprazole recrystallization method, is characterized in that, adopts the mixed solvent of organic solvent of ketone and ring ether organic solvent to carry out recrystallization.
2. method according to claim 1, is characterized in that, described organic solvent of ketone is selected from one or more in acetone, methylethylketone, pimelinketone, butanone, espeleton, mibk.
3. method according to claim 2, is characterized in that, described organic solvent of ketone is selected from one or more in acetone, pimelinketone, methylethylketone, butanone.
4. method according to claim 1, is characterized in that, described ring ether organic solvent be selected from tetrahydrofuran (THF), 1, one or both in 4-dioxane.
5. method according to claim 1, it is characterized in that, specifically comprise the following steps: by Sodium rabeprazole dissolving crude product in the mixed solvent of organic solvent of ketone and ring ether organic solvent, adopt the method for cooling to make Sodium rabeprazole crystallization, filter and obtain Sodium rabeprazole crystallization.
6. method according to claim 1, is characterized in that, the volume ratio of organic solvent of ketone and ring ether organic solvent is 3:1 ~ 8:1.
7. method according to claim 6, is characterized in that, the volume ratio of organic solvent of ketone and ring ether organic solvent is 5:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410211916.1A CN105085481B (en) | 2014-05-19 | 2014-05-19 | A kind of recrystallization method of RABEPRAZOLE SODIUM |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410211916.1A CN105085481B (en) | 2014-05-19 | 2014-05-19 | A kind of recrystallization method of RABEPRAZOLE SODIUM |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105085481A true CN105085481A (en) | 2015-11-25 |
| CN105085481B CN105085481B (en) | 2017-09-29 |
Family
ID=54566898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410211916.1A Active CN105085481B (en) | 2014-05-19 | 2014-05-19 | A kind of recrystallization method of RABEPRAZOLE SODIUM |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105085481B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501238A (en) * | 2017-07-31 | 2017-12-22 | 上药康丽（常州）药业有限公司 | A kind of process for purification of Rabeprazole |
| CN112834628A (en) * | 2019-11-22 | 2021-05-25 | 扬子江药业集团有限公司 | Method for determining rabeprazole sodium and impurities thereof by high performance liquid chromatography |
| CN113336741A (en) * | 2021-05-07 | 2021-09-03 | 湖南德虹制药有限公司 | Rabeprazole sodium anhydrate crystal form and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008155780A2 (en) * | 2007-06-21 | 2008-12-24 | Matrix Laboratories Ltd | Improved process for the preparation of pure rabeprazole |
| WO2009116072A2 (en) * | 2008-02-08 | 2009-09-24 | Ipca Laboratories Limited | Process for preparation of pyridinylmethylsulphinyl benzimidazole compounds and pyridine intermediates |
| US20100121068A1 (en) * | 2008-11-11 | 2010-05-13 | Chin-Tsai Fan | Process for preparing rabeprazole sodium |
| CN102584793A (en) * | 2012-01-13 | 2012-07-18 | 山东罗欣药业股份有限公司 | Rabeprazole sodium crystal compound and preparing method thereof |
-
2014
- 2014-05-19 CN CN201410211916.1A patent/CN105085481B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008155780A2 (en) * | 2007-06-21 | 2008-12-24 | Matrix Laboratories Ltd | Improved process for the preparation of pure rabeprazole |
| WO2009116072A2 (en) * | 2008-02-08 | 2009-09-24 | Ipca Laboratories Limited | Process for preparation of pyridinylmethylsulphinyl benzimidazole compounds and pyridine intermediates |
| US20100121068A1 (en) * | 2008-11-11 | 2010-05-13 | Chin-Tsai Fan | Process for preparing rabeprazole sodium |
| CN102584793A (en) * | 2012-01-13 | 2012-07-18 | 山东罗欣药业股份有限公司 | Rabeprazole sodium crystal compound and preparing method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501238A (en) * | 2017-07-31 | 2017-12-22 | 上药康丽（常州）药业有限公司 | A kind of process for purification of Rabeprazole |
| CN112834628A (en) * | 2019-11-22 | 2021-05-25 | 扬子江药业集团有限公司 | Method for determining rabeprazole sodium and impurities thereof by high performance liquid chromatography |
| CN113336741A (en) * | 2021-05-07 | 2021-09-03 | 湖南德虹制药有限公司 | Rabeprazole sodium anhydrate crystal form and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105085481B (en) | 2017-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107957458B (en) | Detection method of related substances of omeprazole enteric capsule | |
| CN105085481A (en) | Recrystallization method of rabeprazole sodium | |
| CN106706768B (en) | Method for separating and measuring empagliflozin and related substances thereof | |
| CN103232438B (en) | Pantoprazole sodium and preparation method thereof | |
| CN105153124B (en) | A kind of preparation method of candesartan Cilexetil | |
| CN103087048B (en) | Method for purifying esomeprazole sodium | |
| CN104887673B (en) | A kind of pharmaceutical composition containing Esomeprazole sodium and preparation method thereof | |
| CN107628959A (en) | Choline eutectic solvent, preparation method and the application in trollflower flavone c-glycoside is extracted | |
| US20110046213A1 (en) | Production of Delta 9 Tetrahydrocannabinol | |
| CN102206218B (en) | Method for purifying high-purity pemetrexed disodium | |
| CN105130955A (en) | Preparation method of Vonoprazan fumarate | |
| CN108456168A (en) | The C of a kind of structure novel19Diterpene alkaloid and application thereof | |
| CN102351847B (en) | Industrial method for refining esomeprazole sodium salt | |
| CN105017218A (en) | R-lansoprazole crystal form and preparation method therefor | |
| CN104387393A (en) | Preparation method of sitagliptin impurity | |
| CN110927278B (en) | Improved method for separating imidapril hydrochloride related substances | |
| CN103664887B (en) | The preparation method of Esomeprazole sodium | |
| CN110927279A (en) | Method for separating imidapril hydrochloride related substances | |
| CN102952119B (en) | Sodium rabeprazole preparation method | |
| CN103788068B (en) | Dystectic chiral benzimidazole compound sodium salt, preparation method and its usage | |
| CN104535675A (en) | Method for determining cumene hydroperoxide impurity | |
| CN110627771B (en) | Preparation method of esomeprazole thioether | |
| CN108017601A (en) | A kind of method of refined ranitidine alkali | |
| CN105061398B (en) | A kind of refining methd of Esomeprazole sodium | |
| CN112321642A (en) | Ruidexiwei related substance and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |