CN114942283B - Inspection method of 2-n-butyl-4-chloro-5-formyl related substances - Google Patents
Inspection method of 2-n-butyl-4-chloro-5-formyl related substances Download PDFInfo
- Publication number
- CN114942283B CN114942283B CN202210478281.6A CN202210478281A CN114942283B CN 114942283 B CN114942283 B CN 114942283B CN 202210478281 A CN202210478281 A CN 202210478281A CN 114942283 B CN114942283 B CN 114942283B
- Authority
- CN
- China
- Prior art keywords
- solution
- mzq
- chloro
- butyl
- formyl
- 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
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
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
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 Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
The invention belongs to the technical field of medicine analysis, in particular to a method for detecting 2-n-butyl-4-chloro-5-formyl related substances, which aims to solve the detection problem of the 2-n-butyl-4-chloro-5-formyl related substances, and provides a convenient, efficient and accurate detection method.
Description
Technical Field
The invention belongs to the technical field of medicine analysis, and particularly relates to a method for detecting 2-n-butyl-4-chloro-5-formyl related substances.
Background
Imidazole aldehyde, chinese name: 2-n-butyl-4-chloro-5-formyl is a key intermediate of sartan, namely an angiotensin II receptor Antagonist (ARB) antihypertensive drug, and is a novel antihypertensive drug subsequent to an angiotensin converting enzyme inhibitor. Through the specific binding with the AT1 receptor in the angiotensin II receptor, the angiotensin II can not be combined with the AT1 receptor, thereby blocking arterial vasoconstriction, inhibiting sympathetic nerve excitation and promoting blood pressure reduction. The medicament has the advantages of obvious antihypertensive effect, long acting time, high bioavailability, good tolerance, low adverse reaction incidence rate, protective effect on target organs and the like since 20 years ago, and becomes one of the antihypertensive medicaments commonly applied clinically.
In order to ensure the safety of a supply chain and improve the competitiveness, a plurality of large companies start to be self-sufficient and independently research and develop sartan raw material medicines, which puts higher requirements on the quality of an intermediate imidazole aldehyde of the sartan raw material medicines, and according to the general imidazole aldehyde synthesis process route, the easy-to-produce process impurity N- (1-iminopentyl) -glycine (MZQ-3) is neededAnd byproduct impurity 2-butyl-5-chloro-1H-imidazole (MZQ-IM-3)And the effective control is carried out, so that the quality control of the imidazole aldehyde is effectively ensured.
The detection method of related substances N- (1-iminopentyl) -glycine (MZQ-3) and 2-butyl-5-chloro-1H-imidazole (MZQ-IM-3) in imidazole aldehyde is not disclosed in any literature, the detection method of related substances of 2-N-butyl-4-chloro-5-formyl is disclosed for the first time, and a convenient, efficient and accurate detection method is provided for solving the detection problem of related substances of 2-N-butyl-4-chloro-5-formyl, and can detect the content of related substances of 2-N-butyl-4-chloro-5-formyl, so that the medication safety is effectively ensured, and the quality control of 2-N-butyl-4-chloro-5-formyl is facilitated.
Disclosure of Invention
The invention provides a detection method of 2-n-butyl-4-chloro-5-formyl related substances, which is convenient, efficient and accurate, and can be used for detecting the 2-n-butyl-4-chloro-5-formyl related substances, thereby effectively guaranteeing medication safety and facilitating quality control of the 2-n-butyl-4-chloro-5-formyl.
In order to achieve the above purpose, the present invention provides the following technical solutions:
a method for detecting a 2-n-butyl-4-chloro-5-formyl related substance, the method comprising the steps of:
(1) Preparing solutions, and respectively preparing a blank solution, a system applicability solution and a test solution.
(2) The measuring method comprises the following steps: measuring 2-n-butyl-4-chloro-5-formyl related substances by adopting a liquid chromatography, respectively adding a blank solution, a system applicability solution and a test solution after the system is stable, and recording a chromatogram;
the chromatographic conditions are as follows: waters Xbridge Shield RP18 column of 4.6X15mm3.5 μm or equivalent performance, sample injection amount: 15 μl, column temperature: 25 ℃, flow rate: 0.8ml/min, mobile phase acetonitrile: the water system is a mobile phase, and gradient elution is adopted.
Further, the blank solution was 5% acetonitrile, and the system applicability solution: taking a proper amount of 2-N-butyl-4-chloro-5-formyl standard substance, placing the standard substance into a volumetric flask, adding a proper amount of acetonitrile for dissolution, then transferring a proper amount of N- (1-iminopentyl) -glycine and 2-butyl-5-chloro-1H-imidazole impurity solution into the volumetric flask, diluting to a scale with purified water, and performing test on the solution: taking a proper amount of 2-n-butyl-4-chloro-5-formyl sample, placing the sample into a volumetric flask, adding a proper amount of acetonitrile for dissolving, diluting to a scale with purified water, and shaking uniformly.
Further, the mobile phase gradient process is as follows:
to ensure the accuracy of this method, methodological verification of this method was performed: system applicability, specificity (separation and sample recovery), limit of detection and quantification, linearity and range, precision and solution stability, and the methodological validation results are as follows:
the invention provides a convenient, efficient, economic and accurate detection method for detecting related substances and purity of an imidazole aldehyde which is a sartan intermediate, and the method can effectively detect the related substances of the imidazole aldehyde, so that the quality control of the imidazole aldehyde is effectively ensured.
Drawings
FIG. 1 is a blank solution chart of the present invention
FIG. 2 is a diagram of a solution for the applicability of the system of the present invention
FIG. 3 is a graph of a test solution according to the present invention
FIG. 4 is a liquid chromatogram of comparative example 1 of the present invention
FIG. 5 is a liquid chromatogram of comparative example 2 of the present invention
FIG. 6 is a liquid chromatogram of comparative example 3 of the present invention
FIG. 7 is a liquid chromatogram of comparative example 4 of the present invention
FIG. 8 is a liquid chromatogram of comparative example 5 of the present invention
Detailed Description
The invention is further illustrated by the following examples, which are not intended to be limiting.
Example 1:
(1) Preparing a solution:
dilution liquid: 5% acetonitrile
Blank solution: dilution liquid
MZQ-IM-3 stock: about 30mg of MZQ-IM-3 reference substance is weighed, precisely weighed, placed in a 200mL measuring flask, dissolved and diluted to a scale with a diluent, and shaken well. (MZQ-IM-3 concentration: 0.15 mg/ml)
MZQ-3 stock: about 30mg of MZQ-3 reference substance is weighed, precisely weighed, placed in a 200mL measuring flask, dissolved and diluted to a scale with a diluent, and shaken well. (MZQ-3 concentration: 0.15 mg/ml)
Impurity stock solution: 5.0ml of each of MZQ-IM-3 stock solution and MZQ-3 stock solution was measured separately, placed in a 50ml measuring flask, dissolved with the diluent and diluted to the scale, and shaken well. ( MZQ-IM-3 concentration: 15. Mu.g/ml; MZQ-3 concentration: 15. Mu.g/ml )
System applicability solution: about 30mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, 5.0mL of acetonitrile is added to dissolve, 10.0mL of impurity stock solution is precisely measured and placed in the measuring flask, diluted to a scale with purified water, and shaken well. (MZQ-IM-3 concentration: 1.5. Mu.g/ml; MZQ-3 concentration: 1.5. Mu.g/ml; MZQ concentration: 0.3 mg/ml);
MZQ positioning solution: about 30mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale and shaken well. (MZQ concentration: 0.3 mg/ml)
MZQ-IM-3 localization solution: accurately measuring MZQ-IM-3 stock solution 1.0ml, placing in a 100ml measuring flask, adding diluent, diluting to scale, and shaking. (concentration: 1.5. Mu.g/ml)
MZQ-3 positioning solution: accurately measuring MZQ-3 stock solution 1.0ml, placing in a 100ml measuring flask, adding diluent, diluting to scale, and shaking. (concentration: 1.5. Mu.g/ml)
Impurity control solution: accurately measuring MZQ-3 stock solution and MZQ-IM-3 stock solution, placing 1.0ml each in a 100ml measuring flask, adding diluent, diluting to scale, and shaking. ( MZQ-IM-3 concentration: 1.5. Mu.g/ml; MZQ-3 concentration: 1.5. Mu.g/ml )
MZQ test solution: about 30mg of a MZQ sample is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale, and shaken well. (MZQ concentration: 0.3 mg/ml)
Degree of separation solution: about 30mg of a MZQ sample is weighed, precisely weighed, placed in a 100mL measuring flask, 5mL of acetonitrile is added to dissolve the sample, 10.0mL of impurity stock solution is precisely measured and placed in the measuring flask, diluted to a scale with purified water, and shaken well. (MZQ-IM-3 concentration: 1.5. Mu.g/ml; MZQ-3 concentration: 1.5. Mu.g/ml; MZQ concentration: 0.3 mg/ml);
LOQ test solution: precisely measuring 5.0ml of MZQ stock solution, placing in a 100ml measuring flask, adding diluent to dilute to scale, and shaking; then precisely measuring 1.0ml of the solution and 1.0ml of the impurity stock solution, placing the solution into a 100ml measuring flask, adding the diluent to dilute to a scale, and shaking uniformly. ( MZQ-IM-3 concentration: 0.15 μg/ml; MZQ-3 concentration: 0.15 μg/ml; MZQ concentration: 0.15. Mu.g/ml )
LOQ solution: according to the S/N value obtained by the LOQ test solution, the dilution ratio is adjusted to the S/N value of each component not less than 10. From stock solution to LOQ solution, 6 parts were arranged in parallel.
LOD solution: precisely measuring 3.0ml of LOQ solution, placing into a 10ml measuring flask, adding diluent to dilute to scale, and shaking;
linear mixed stock: MZQ-IM-3 stock solution 10mL, MZQ-3 stock solution 10mL and MZQ stock solution 5mL were respectively measured, placed in a 100mL measuring flask, dissolved and diluted to scale with a diluent, and shaken well. (MZQ concentration: 15. Mu.g/ml; MZQ-IM-3 concentration: 15. Mu.g/ml; MZQ-3 concentration: 15. Mu.g/ml);
linear 50% solution: precisely measuring 1.0ml of the linear mixed stock solution in a 20ml measuring flask, adding the diluent to dissolve and dilute to a scale, and shaking uniformly. ( MZQ concentration: 0.75 μg/ml; MZQ-3 concentration: 0.75 μg/ml; MZQ-IM-3 concentration: 0.75 μg/ml )
Linear 120% solution: 3.0ml of the linear mixed stock solution is precisely measured in a 25ml measuring flask, diluted solution is added for dissolution and dilution to a scale, and shaking is carried out uniformly. ( MZQ concentration: 1.8. Mu.g/ml; MZQ-3 concentration: 1.8. Mu.g/ml; MZQ-IM-3 concentration: 1.8. Mu.g/ml )
Linear 150% solution: 3.0ml of the linear mixed stock solution is precisely measured in a 20ml measuring flask, diluted solution is added for dissolution and dilution to a scale, and shaking is carried out uniformly. (MZQ concentration: 2.25. Mu.g/ml; MZQ-3 concentration: 2.25. Mu.g/ml; MZQ-IM-3 concentration: 2.25. Mu.g/ml);
MZQ linear 80% solution: about 24mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale and shaken well. (MZQ concentration: 0.24 mg/ml)
MZQ linear 90% solution: about 27mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale and shaken well. (MZQ concentration: 0.27 mg/ml)
MZQ linear 100% solution: about 30mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale and shaken well. (MZQ concentration: 0.3 mg/ml)
MZQ linear 110% solution: about 33mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale and shaken well. (MZQ concentration: 0.33 mg/ml)
MZQ linear 120% solution: about 36mg of MZQ reference substance is weighed, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 5mL of acetonitrile, dissolved by purified water, diluted to a scale and shaken well. (MZQ concentration: 0.36 mg/ml)
Repetitive solution: about 30mg of a MZQ sample is weighed, precisely weighed, placed in a 100ml measuring flask, dissolved by adding 5ml of acetonitrile, diluted to a scale with purified water, and shaken well. (MZQ concentration: 0.3 mg/ml)
6 parts of a repetitive solution was prepared in the same manner.
Chromatographic conditions:
chromatographic column: waters Xbridge Shield RP 18A 4.6X105 mm3.5 μm or equivalent chromatography column
Mobile phase a: purified water
Mobile phase B: acetonitrile
Gradient elution procedure:
detection wavelength: column temperature at 210 nm: 25 DEG C
Sample injection volume: 15 μl flow rate: 0.8mL/min
(1) The measuring method comprises the following steps:
after the system is stable, at least 2 needles of blank solution are fed, 1 needle of test solution is fed, and finally 1 needle of system applicability solution is fed into the sequence, and the chromatogram is recorded.
And (3) calculating: calculated by an area normalization method. Wherein RRT is about 1.37 chromatographic peak is toluene peak, and does not participate in calculation of results.
And (3) judging results:
example 2: system applicability
The system applicability is realized by measuring the RSD of the peak areas of MZQ, MZQ-3 and MZQ-IM-3 in a 6-needle system applicability solution, wherein the RSD of the peak areas of a 6-needle reference solution is required to be less than or equal to 2.0% of the separation degree between each known component and adjacent peaks; MZQ-3, and RSD of the peak area of MZQ-IM-3 is less than or equal to 5.0%; the separation degree between each known component and the adjacent peak is not less than 1.5, at least 2 needles of blank solution and 6 needles of system applicability solution are added after the system is stable, and the chromatogram is recorded.
Example 3: specialization of
The specificity of the method is realized by testing whether the blank solution has interference to detection, the separation degree between each component in the separation degree solution and the adjacent peak, the peak purity of MZQ in the separation degree solution and the known impurity recovery rate, and the specificity is required to be realized without interference to detection, and the separation degree between each known component in the separation degree solution and the adjacent peak is not less than 1.5; the purity of MZQ peak in the separation degree solution is not less than 990, after the system is stable, the system applicability is established, at least 2 needles are fed into the blank solution, 1 needle is positioned for each solution, 1 needle is MZQ for the test solution, 3 needles are used for the impurity control solution, 3 needles are used for the separation degree solution, and finally 1 needle is fed into the system applicability solution for the sequence, and the chromatogram is recorded.
Example 4: limit of detection and limit of quantification
The detection limit is obtained by detecting that the ratio of the response signals of all components to the noise is more than or equal to 3, the quantitative limit is obtained by detecting that the ratio of the response signals of all components to the noise is more than or equal to 10, after the system is stable, the system applicability is established, at least 2 needles of blank solution, 1 needle of LOQ test solution, 1 needle of 6 parts of LOQ solution, 1 needle of LOD solution and finally 1 needle of system applicability solution are added into the sequence, and the chromatogram is recorded.
Example 5: linearity of
Impurity linearity: 6 concentration points in the LOQ-150% index concentration range are plotted by taking the concentration as an abscissa and the peak area as an ordinate, the linear correlation coefficient R2 and intercept deviation of the required curve accord with acceptable standards, wherein unknown impurities are replaced by MZQ, the impurities are required to be linear in the LOQ-150% index concentration range, and the linear correlation coefficient R of the required curve is required 2 And the absolute value of the Y-axis intercept is more than or equal to 0.99, the response value is less than 25.0% when the absolute value of the Y-axis intercept is relative to 100% concentration, after the system is stable, the system applicability is established, at least 2 needles of blank solution are fed, 3 needles of linear test solution with each concentration are fed, and finally 1 needle of system applicability solution is fed into the sequence, and a chromatogram is recorded.
Principal component linearity: 5 concentration points in the index concentration range of 80% -120%, wherein the concentration is taken as an abscissa, the peak area is taken as an ordinate to draw a curve, and the main requirement is thatThe components are linear within the concentration range of 80-120% of the sample, and the linear correlation coefficient R of the curve is required 2 And after the system is stable, establishing the applicability of the system, feeding at least 2 needles into a blank solution, feeding 3 needles into each concentration linear test solution, feeding 1 needle of system applicability solution into the sequence, and recording a chromatogram.
Example 6: precision of
Repeatability: repeatability is realized by testing RSD with purity and impurity content of 6 parts of repetitive solution MZQ, after the system is stable, establishing system applicability, feeding at least 2 needles into blank solution, feeding 1 needle into each of 6 parts of repetitive solution, feeding 1 needle into system applicability solution finally, and recording a chromatogram.
Reproducibility: reproducibility is to examine the influence of different laboratories, different times, different equipment and different detection personnel on the detection result.
Example 7: solution stability
And (3) observing the rule of time variation of the detection result after the test solution is placed for 0 day, 1 day, 2 days and 3 days at room temperature, and providing a basis for the placement time of the test solution during detection.
Comparative example 1: the following chromatographic conditions were used to determine the relevant material in imidazole aldehyde, and as seen in FIG. 4, impurity MZQ-3 and impurity MZQ-IM-3 were essentially absent, and the MZQ-IM-3 impurity peak was not peak-forming.
From the point of view of no retention of impurities in comparative example 1, the process optimization was considered from the following 4 aspects: 1) Enhancing impurity retention by using hydrophilic chromatography column HILIC; 2) Enhanced retention of impurities with a chromatographic column resistant to 100% aqueous phase; 3) Ion pairing agents (sodium octanesulphonate) are used to enhance impurity retention; 4) Ion pair reagent (triethylamine) was used to enhance impurity retention.
Comparative example 2: the retention of impurities was enhanced by using a chromatographic column HILIC having a hydrophilic effect, and the retention times of impurities MZQ-3 and MZQ-IM-3 were enhanced but the retention times of main peaks were weaker as seen in FIG. 5, using the following chromatographic conditions for measuring the related substances in imidazole aldehyde.
Comparative example 3: enhanced retention of impurities by chromatography with a 100% aqueous phase resistant column, the retention time of impurities MZQ-3 was enhanced but the impurity peaks were branched off and solvent effect was seen from figure 6 using the following chromatographic conditions to determine the related substances in imidazole aldehyde; the mobile phase is purified water and acetonitrile, which is convenient to operate, efficient and economical.
Comparative example 4: ion-pair reagent (sodium octanesulphonate) was used to enhance retention of impurities, and the following chromatographic conditions were used to determine the relevant materials in imidazole aldehyde, and as seen in FIG. 7, the retention time of impurities MZQ-3 and MZQ-IM-3 was enhanced, but the blank had a larger gradient peak under gradient conditions, and the economic cost of ion-pair reagent sodium octanesulphonate was higher.
Comparative example 5: ion-pair reagent (triethylamine) was used to enhance impurity retention, and the following chromatographic conditions were used to determine the relevant material in imidazole aldehyde, with substantially no impurity MZQ-3 retained as seen in fig. 8.
By comparing the comparative examples 1 to 5, the comparative example 3 (the retention of impurities is enhanced by a chromatographic column which can endure 100% aqueous phase) was further optimized from the comprehensive consideration of the retention time of impurities, economy and convenience and high efficiency, and the final analysis method was determined to be the detection method of the present invention.
Claims (2)
1. A method for inspecting a 2-n-butyl-4-chloro-5-formyl related substance, comprising the steps of:
(1) Preparing a solution, namely preparing a blank solution, a system applicability solution and a test solution respectively;
(2) The measuring method comprises the following steps: measuring 2-n-butyl-4-chloro-5-formyl related substances by adopting a liquid chromatography, respectively adding a blank solution, a system applicability solution and a test solution after the system is stable, and recording a chromatogram; the chromatographic conditions are as follows: waters Xbridge Shield RP18 sample introduction amount of 4.6X105 mm3.5 μm: 15 μl, column temperature: 25 ℃, flow rate: 0.8ml/min, mobile phase acetonitrile: the water system is a mobile phase, and gradient elution is adopted;
the mobile phase gradient process is as follows:
the related substances are N- (1-iminopentyl) -glycine and 2-butyl-5-chloro-1H-imidazole.
2. The method according to claim 1, characterized in that: the blank solution is 5% acetonitrile; the system applicability solution: taking a proper amount of 2-N-butyl-4-chloro-5-formyl standard substance, placing the standard substance into a volumetric flask, adding a proper amount of acetonitrile for dissolution, then transferring a proper amount of N- (1-iminopentyl) -glycine and 2-butyl-5-chloro-1H-imidazole impurity solution into the volumetric flask, and diluting the solution to a scale with purified water; the test solution: taking a proper amount of 2-n-butyl-4-chloro-5-formyl sample, placing the sample into a volumetric flask, adding a proper amount of acetonitrile for dissolving, diluting to a scale with purified water, and shaking uniformly.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210478281.6A CN114942283B (en) | 2022-05-05 | 2022-05-05 | Inspection method of 2-n-butyl-4-chloro-5-formyl related substances |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210478281.6A CN114942283B (en) | 2022-05-05 | 2022-05-05 | Inspection method of 2-n-butyl-4-chloro-5-formyl related substances |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114942283A CN114942283A (en) | 2022-08-26 |
CN114942283B true CN114942283B (en) | 2023-05-02 |
Family
ID=82908014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210478281.6A Active CN114942283B (en) | 2022-05-05 | 2022-05-05 | Inspection method of 2-n-butyl-4-chloro-5-formyl related substances |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114942283B (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06116243A (en) * | 1992-10-08 | 1994-04-26 | Nippon Synthetic Chem Ind Co Ltd:The | Production of 2-alkylformylimidazole |
CN103901117A (en) * | 2012-12-27 | 2014-07-02 | 江苏康缘药业股份有限公司 | Method for detecting dronedarone hydrochloride |
CN114216988A (en) * | 2021-12-23 | 2022-03-22 | 珠海润都制药股份有限公司 | Method for detecting 4- (methylamino) -1- (3-pyridyl) -1-butanone hydrochloride related substances |
-
2022
- 2022-05-05 CN CN202210478281.6A patent/CN114942283B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06116243A (en) * | 1992-10-08 | 1994-04-26 | Nippon Synthetic Chem Ind Co Ltd:The | Production of 2-alkylformylimidazole |
CN103901117A (en) * | 2012-12-27 | 2014-07-02 | 江苏康缘药业股份有限公司 | Method for detecting dronedarone hydrochloride |
CN114216988A (en) * | 2021-12-23 | 2022-03-22 | 珠海润都制药股份有限公司 | Method for detecting 4- (methylamino) -1- (3-pyridyl) -1-butanone hydrochloride related substances |
Non-Patent Citations (2)
Title |
---|
Gareth J. Griffiths等.Novel Syntheses of 2-Butyl-5-chloro-3H-imidazole-4-carbaldehyde:A Key Intermediate for the Synthesis of the Angiotensin II Antagonist Losartan.《J. Org. Chem》.1999,第64卷8084-8089. * |
丁逸梅 ; 陆春晓 ; 崔萍 ; 王德才 ; 邱江凯 ; .盐酸决奈达隆有关物质的HPLC法测定.中国医药工业杂志.2013,(10),1018-1020. * |
Also Published As
Publication number | Publication date |
---|---|
CN114942283A (en) | 2022-08-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108593831B (en) | HPLC detection method of fasudil hydrochloride related substances | |
CN112782327B (en) | Method for separating and determining carbocisteine and impurities thereof by liquid chromatography | |
CN113533552A (en) | Method for synchronously detecting ARR (arginine-citrate receptor) drugs influenced in renin activity detection process by liquid chromatography-tandem mass spectrometry | |
CN113433242A (en) | Detection method for Molnopiravir content and related substances | |
CN109580821B (en) | Method for detecting impurity succinic acid in S-benzylsuccinic acid | |
CN108152418A (en) | The HPLC detection methods of ketorolac tromethamine or/and impurity in ketorolac tromethamine or its preparation | |
CN111077232B (en) | Inspection method of Sacubitril valsartan sodium related substances | |
CN113125611B (en) | Method for detecting content of impurity 6-formyl pterin folic acid | |
CN114942283B (en) | Inspection method of 2-n-butyl-4-chloro-5-formyl related substances | |
CN113533578A (en) | Quality control method of related substances in bromhexine hydrochloride tablets | |
CN113702514A (en) | Method for determining atorvastatin calcium related impurity I | |
CN110824059B (en) | Detection method of formyl impurities in febuxostat | |
CN112924601B (en) | Method for detecting lincomycin impurity E in lincomycin hydrochloride injection by high performance liquid chromatography-evaporative light method | |
CN114689737A (en) | Analysis method of S-o-chlorophenyl glycine methyl ester tartrate related substances | |
CN113466360B (en) | Azilsartan 6 related substance detection method | |
CN110530992B (en) | Method for testing optical isomer of levobupivacaine hydrochloride injection | |
CN107884496B (en) | Method for determining content of succinic acid in trelagliptin succinate | |
CN102875449A (en) | Separation method for tirofiban hydrochloride isomer, and metering method for D-configuration tirofiban hydrochloride | |
CN114577913B (en) | Method for detecting rabeprazole chloride in sodium rabeprazole | |
CN117491548A (en) | Detection method of dyclonine hydrochloride related substances | |
CN112924602B (en) | Method for detecting lincomycin impurity F in lincomycin hydrochloride injection by high performance liquid chromatography-evaporative light method | |
CN112858527B (en) | Detection method of related substances of pramipexole dihydrochloride sustained-release tablets | |
CN109580822B (en) | Method for detecting cis-1, 2-cyclohexanediamine impurity in levo-trans-1, 2-cyclohexanediamine | |
CN114280168A (en) | HPLC method for detecting voriconazole concentration in serum | |
CN107870210A (en) | The method for determining Li Gelieting contents in Li Gelieting bulk drugs |
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 |