CN109134430A - A kind of method that HPLC method prepares Rabeprazole impurity - Google Patents
A kind of method that HPLC method prepares Rabeprazole impurity Download PDFInfo
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- CN109134430A CN109134430A CN201810914157.3A CN201810914157A CN109134430A CN 109134430 A CN109134430 A CN 109134430A CN 201810914157 A CN201810914157 A CN 201810914157A CN 109134430 A CN109134430 A CN 109134430A
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- 238000000034 method Methods 0.000 title claims abstract description 50
- 229960004157 rabeprazole Drugs 0.000 title claims abstract description 37
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 239000012535 impurity Substances 0.000 title claims abstract description 35
- 238000004128 high performance liquid chromatography Methods 0.000 title claims abstract description 21
- 239000000126 substance Substances 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- 239000012071 phase Substances 0.000 claims description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000010790 dilution Methods 0.000 claims description 9
- 239000012895 dilution Substances 0.000 claims description 9
- 238000010828 elution Methods 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 7
- 239000005695 Ammonium acetate Substances 0.000 claims description 7
- 235000019257 ammonium acetate Nutrition 0.000 claims description 7
- 229940043376 ammonium acetate Drugs 0.000 claims description 7
- 238000004458 analytical method Methods 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 229910021538 borax Inorganic materials 0.000 claims description 5
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 5
- 239000004328 sodium tetraborate Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000012670 alkaline solution Substances 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 3
- 238000004262 preparative liquid chromatography Methods 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 229910052796 boron Inorganic materials 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 230000020477 pH reduction Effects 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 230000035484 reaction time Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000013076 target substance Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000001711 oxyntic cell Anatomy 0.000 description 2
- 229940126409 proton pump inhibitor Drugs 0.000 description 2
- 239000000612 proton pump inhibitor Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 1
- MCUYHRNUDDANSO-UHFFFAOYSA-N 4-chloro-2,3-dimethyl-1-oxidopyridin-1-ium Chemical compound CC1=C(C)[N+]([O-])=CC=C1Cl MCUYHRNUDDANSO-UHFFFAOYSA-N 0.000 description 1
- 208000012639 Balance disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 1
- 108010083204 Proton Pumps Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- CDMADVZSLOHIFP-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane;decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 CDMADVZSLOHIFP-UHFFFAOYSA-N 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 231100000880 dysequilibrium Toxicity 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention discloses a kind of methods that HPLC method prepares Rabeprazole impurity, belong to organic chemistry and pharmaceutical synthesis field, and preparation method provided by the invention, simple and convenient, the reaction time is short, and target substance purity is high is conducive to the miscellaneous Quality Research of Rabeprazole.The present invention prepares target impurity using Rabeprazole bulk pharmaceutical chemicals as raw material, using HPLC method, and analyzes the chemical property of the impurity, provides foundation for assessment the qualitative of Rabeprazole bulk pharmaceutical chemicals, safety and efficiency.
Description
Technical field
The invention belongs to organic chemistry and pharmaceutical synthesis fields more particularly to a kind of HPLC method to prepare Rabeprazole impurity
Method.
Background technique
Peptic ulcer is common, multiple disease of digestive system, takes place mostly in stomach and duodenum, is a kind of chronic
Ulcer.It is fallen ill and dysequilibrium between mucosa injury and protection mechanism is related.Rabeprazole is a kind of novel anti-ulcer medicament,
Belong to proton pump inhibitor, the type drug is the latest generation acid-suppressing medicine of current clinical use, and Acidinhibitor is powerful and holds
Long.Proton pump acts on the last one link during gastric acid secretion, is absorbed into blood in vivo and reaches parietal cell later
Secretory tubyle, be changed into active material under acidic environment, act on H+-K+-ATP enzyme and make its inactivation, lead to parietal cell
Interior hydrogen ion cannot be transferred to gastral cavity and reduce gastric acid secretion, so that pH value increases in gastric juice, to reach acid suppression
Effect.Compared with other proton pump inhibitors, the bioavilability of Rabeprazole is higher, active very fast, onset time faster, make
With more longlasting, since the advent of the world just endures concern to the fullest extent.Rabeprazole impurity be generated in Rabeprazole synthesis process one kind it is miscellaneous
Matter, type is complicated, causes certain influence to the quality of drug, safety, and also related with efficiency in a few cases.Cause
This, it can be bulk pharmaceutical chemicals that control impurity level, which carries out the research such as relevant physics, chemistry, biological property to Rabeprazole impurity,
The quality control of Rabeprazole provides control sample, to promote the research of Rabeprazole.The Rabeprazole impurity being currently known
It is several to have ten, but is seldom related to the method for preparing Rabeprazole impurity in the literature, has been short of the research to its physico-chemical property.
Only disclosed in 107663192 A of patent document CN it is a kind of with 2,3- dimethyl -4- chloropyridine-N- oxide and
2-Chlorobenzimidazole is the method for Material synthesis Rabeprazole impurity (X), and synthetic route is as follows:
Reaction route described in this method is too long, and the reaction time is long, is unfavorable for industrial production.
Summary of the invention
The present invention provides a kind of method that HPLC method prepares Rabeprazole impurity, this method simple process, reaction time
Short, target substance purity is high is conducive to the miscellaneous Quality Research of Rabeprazole.
In order to achieve the above object, the present invention uses following scheme:
A kind of method that HPLC method prepares Rabeprazole impurity, comprising the following steps:
(1) it takes Rabeprazole bulk pharmaceutical chemicals to be placed in volumetric flask, and acid solution is added, alkaline solution is added after the completion of acidification and carries out
It neutralizes, dilution constant volume is then added, obtains reaction solution；
(2) mobile phase is prepared, by the way of high performance liquid chromatography (HPLC) separation, reaction solution is analyzed；
(3) target impurity is prepared using preparative liquid chromatography instrument, and obtains target impurity pure material I after isolating and purifying, knot
Structure formula is as follows:
。
It is using Rabeprazole bulk pharmaceutical chemicals as raw material in above step.
Further, acid solution described in step (1) is hydrochloric acid, sulfuric acid, any one in nitric acid, preferably hydrochloric acid；
Alkaline solution is sodium hydroxide, sodium borohydride, any one in sodium carbonate, preferably sodium hydroxide.
Further, dilution described in step (1) is made of A and B, A be water, 0.1mol/L sodium hydroxide solution,
The mixed liquor of 0.1mol/L sodium tetraborate solution composition, the volume ratio of 3 kinds of components are as follows: 625:255:120；B is acetonitrile；A's and B
Volume ratio are as follows: 80:20.
Further, the 0.1mol/L sodium hydroxide solution of dilution described in step (1) or 0.1mol/L sodium tetraborate
Solution adjusts PH to 11.3.
Further, mobile phase described in step (2) is the water of 0.065mol/L ammonium acetate by two phase composition of C and D, C phase
The mixed liquor of solution and acetonitrile, volume ratio 95:5；D phase is the mixing of the aqueous solution and methanol of 0.065mol/L ammonium acetate
Liquid, volume ratio 15:85.
Further, reaction solution analysis condition in step (2) are as follows: the mixed phase of mobile phase C, D two-phase, C18 chromatographic column (column
Specification: 5 μm, 250*4.6mm or 5 μm, 150*4.6mm), Detection wavelength 290nm, flow velocity 1.0ml/min, column temperature is
35℃。
Further, gradient elution mode is taken in reaction solution analysis in step (2): time 30min, in 0 ~ 20min, C
Phase content in 100% ~ 0% even variation, D phase content in 0% ~ 100% even variation, keep later two minutes it is constant, 22 ~
It is 0% that C phase content, which is 100%, D phase content, in 30min.
Further, the gradient elution process is as follows:
。
Further, using C18 chromatographic column (column specification: 5 μm, 20*250 mm) in step (3), preparation method is such as step
(2) analyzing detecting method in carries out the separation and collection of target peak using gradient elution mode.
Further, target impurity need to improve stability in such a way that low temperature rotates removal organic phase, obtain high-purity height
The Rabeprazole target impurity I of stability, the revolving temperature are 15-35 DEG C, preferably 20 DEG C.
The beneficial effects of the present invention are: providing a kind of method that HPLC method prepares Rabeprazole impurity, this method technique
Simply, reaction condition is mild, and the reaction time is short, and yield is high, target substance purity is high, and is convenient for industrialized production.
Detailed description of the invention
Fig. 1 is the liquid chromatogram of reaction solution；
Fig. 2 is the purity detecting liquid chromatogram of object；
Fig. 3 is the purity of object1H-NMR spectrum；
Fig. 4 is object13C-NMR spectrogram.
Specific embodiment
Embodiment 1
Step 1: reaction solution is prepared
The configuration of dilution: weighing sodium hydroxide 0.84g, and sodium borate decahydrate 3.66g adds water to 800ml, uses 0.1mol/
L sodium hydroxide or 0.1mol/L sodium tetraborate solution adjust PH to 11.3, add acetonitrile 200ml, stir evenly to get dilution.
The preparation of reaction solution: taking Rabeprazole bulk pharmaceutical chemicals about 20mg, be placed in 100mL volumetric flask, and 0.2mol/L salt is added
Acid solution 2mL, stand ten minutes later be added 0.2mol/L sodium hydroxide solution 2mL neutralize, add dilution to scale to get
Reaction solution.
Step 2: analysis reaction solution
The preparation of mobile phase: it weighs 0.501g ammonium acetate and is placed in the volumetric flask of 100ml, and add water to graduation mark, obtain
The aqueous solution of 0.065mol/L ammonium acetate, and measure solution 95ml and 5ml acetonitrile and be mixed to get C phase；Similarly prepare
The aqueous solution of 0.065mol/L ammonium acetate, and measure solution 15ml and 85ml methanol and be mixed to get D phase.
Reaction solution analysis condition:
It selects the mixed phase of C, D two-phase as mobile phase, is being analyzed using C18 chromatographic column (column specification: 5 μm, 250*4.6mm)
Reaction solution is analyzed on type liquid chromatograph, Detection wavelength 290nm, flow velocity 1.0ml/min, column temperature is 35 DEG C, ladder
It is as shown in table 1 below to spend elution process:
Table 1
Gradient elution result data is as shown in table 2 below.
Table 2
Conclusion: it determines that target peak occurs at 11.342min, and is separated with other substances.
Step 3: preparation target impurity
According to step 1 the method in embodiment 1, reaction solution is prepared again, and using analysis condition and ladder described in step 2
Spend type of elution, using C18 chromatographic column (column specification: 5 μm, 20*250 mm) on preparative liquid chromatography instrument to target peak into
Row separation and collection, obtain target impurity (I), and carry out at freeze-drying after low temperature (20oC) backspin is boiled off except organic phase
Reason, is stablized and the target impurity of high-purity, HPLC detection target impurity purity are 92.25%.
1H NMR (500MHz, D2O-d6) δ: 8.79~8.78(s, 1H), 7.78~7.60 (s, 2H, Ar-H),
7.58~7.57 (s, 1H, Py-H), 7.37 (s, 2H, Ar-H),4.62~4.60(m, 3H, -CH2O-Py and -NH ),
3.82~3.80(m, 2H, -CH2O-), 3.49 (s, 3H, -OCH3), 2.42 (s, 3H, Py-CH3), 2.33~2.30
(m, 2H, -CH2-).
13C NMR (D2O-d6)δ: 171.1, 165.7, 152.5, 151.2, 143.5, 142.7, 122.2, 122.0,
121.7, 117.0, 110.0, 108.2, 68.8, 68.4, 57.9, 27.9, 23.3, 11.4。
Claims (10)
1. a kind of method that HPLC method prepares Rabeprazole impurity, which comprises the following steps:
It takes Rabeprazole bulk pharmaceutical chemicals to be placed in volumetric flask, and acid solution is added, be added after the completion of acidification in alkaline solution progress
With, it is subsequent that dilution constant volume is added, obtain reaction solution；
Mobile phase is prepared, by the way of high performance liquid chromatography (HPLC) separation, reaction solution is analyzed；
Target impurity is prepared using preparative liquid chromatography instrument, and the high target of acquisition purity high stability is miscellaneous after isolating and purifying
Matter I, structural formula is as follows:
。
2. the method that a kind of HPLC method according to claim 1 prepares Rabeprazole impurity, which is characterized in that step (1)
Described in acid solution be hydrochloric acid, sulfuric acid, any one in nitric acid, preferably hydrochloric acid, alkaline solution are sodium hydroxide, boron hydrogen
Change sodium, any one in sodium carbonate, preferably sodium hydroxide.
3. the method that a kind of HPLC method according to claim 1 prepares Rabeprazole impurity, which is characterized in that step (1)
Described in dilution be made of A and B, A is water, 0.1mol/L sodium hydroxide solution, 0.1mol/L sodium tetraborate solution composition
Mixed liquor, the volume ratio of 3 kinds of components are as follows: 625:255:120；B is acetonitrile；The volume ratio of A and B are as follows: 80:20.
4. the method that a kind of HPLC method according to claim 1 prepares Rabeprazole impurity, which is characterized in that step (1)
Described in dilution need to adjust PH to 11.3 with 0.1mol/L sodium hydroxide solution or 0.1mol/L sodium tetraborate solution.
5. the method that a kind of HPLC method according to claim 1 prepares Rabeprazole impurity, which is characterized in that step (2)
Described in mobile phase by two phase composition of C and D, C phase is the aqueous solution of 0.065mol/L ammonium acetate and the mixed liquor of acetonitrile, body
Product is than being 95:5；D phase is the aqueous solution of 0.065mol/L ammonium acetate and the mixed liquor of methanol, volume ratio 15:85.
6. the method that a kind of HPLC method according to claim 1 prepares Rabeprazole impurity, which is characterized in that step (2)
Middle reaction solution analysis condition are as follows: the mixed phase of mobile phase C, D two-phase, C18 chromatographic column, Detection wavelength 290nm, flow velocity are
1.0ml/min, column temperature are 35 DEG C.
7. the method that a kind of HPLC method according to claim 1 prepares Rabeprazole impurity, which is characterized in that step (2)
Gradient elution mode is taken in middle reaction solution analysis: time 30min, in 0 ~ 20min, C phase content uniformly becomes 100% ~ 0%
Change, D phase content is in 0% ~ 100% even variation, and holding later two minutes constant, and C phase content is 100%, D phase in 22 ~ 30min
Content is 0%.
8. the method that a kind of HPLC method according to claim 7 prepares Rabeprazole impurity, which is characterized in that the gradient
Elution process is as follows:
。
9. the method that a kind of HPLC method according to claim 1-8 prepares Rabeprazole impurity, which is characterized in that
C18 chromatographic column is used in step (3), preparation method is carried out such as analyzing detecting method in step (2) using gradient elution mode
The separation and collection of target peak.
10. according to a kind of method that HPLC method prepares Rabeprazole impurity described in claim 1, which is characterized in that target impurity
The mode of low temperature revolving removal organic phase need to be used to improve stability, the Rabeprazole target for obtaining high-purity high stability is miscellaneous
Matter I, the revolving temperature are 15-35 DEG C, preferably 20 DEG C.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112611815A (en) * | 2020-12-03 | 2021-04-06 | 珠海润都制药股份有限公司 | Method for detecting 2, 3-dimethyl-4-chloropyridine-N-oxidized hydrochloride in rabeprazole sodium |
| 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 |
| CN114609268A (en) * | 2022-02-10 | 2022-06-10 | 南京海纳医药科技股份有限公司 | Method for detecting related substances in dextral rabeprazole sodium bulk drug |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101627996A (en) * | 2009-08-20 | 2010-01-20 | 山东罗欣药业股份有限公司 | Rabeprazole sodium composition and preparation method thereof |
| CN101704811A (en) * | 2009-12-09 | 2010-05-12 | 陶灵刚 | High-purity sodium rabeprazole compound |
| CN107663192A (en) * | 2017-11-03 | 2018-02-06 | 梯尔希（南京）药物研发有限公司 | A kind of preparation method of Rabeprazole impurity |
-
2018
- 2018-08-13 CN CN201810914157.3A patent/CN109134430B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101627996A (en) * | 2009-08-20 | 2010-01-20 | 山东罗欣药业股份有限公司 | Rabeprazole sodium composition and preparation method thereof |
| CN101704811A (en) * | 2009-12-09 | 2010-05-12 | 陶灵刚 | High-purity sodium rabeprazole compound |
| CN107663192A (en) * | 2017-11-03 | 2018-02-06 | 梯尔希（南京）药物研发有限公司 | A kind of preparation method of Rabeprazole impurity |
Non-Patent Citations (1)
| Title |
|---|
| T.V. RAGHAVA RAJU ET AL.: "DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING HPLC METHOD FOR THE ESTIMATION OF RABEPRAZOLE IMPURITIES IN PHARMACEUTICAL DOSAGE FORMS BY DESIGN OF EXPERIMENTS", 《ASIAN J PHARM CLIN RES》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN112611815A (en) * | 2020-12-03 | 2021-04-06 | 珠海润都制药股份有限公司 | Method for detecting 2, 3-dimethyl-4-chloropyridine-N-oxidized hydrochloride in rabeprazole sodium |
| CN112611815B (en) * | 2020-12-03 | 2022-04-08 | 珠海润都制药股份有限公司 | Method for detecting 2, 3-dimethyl-4-chloropyridine-N-oxidized hydrochloride in rabeprazole sodium |
| CN114609268A (en) * | 2022-02-10 | 2022-06-10 | 南京海纳医药科技股份有限公司 | Method for detecting related substances in dextral rabeprazole sodium bulk drug |
| CN114609268B (en) * | 2022-02-10 | 2024-04-16 | 南京海纳医药科技股份有限公司 | Detection method for related substances in sodium rabeprazole bulk drug |
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