CN110045038B - Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method - Google Patents
Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method Download PDFInfo
- Publication number
- CN110045038B CN110045038B CN201910394249.8A CN201910394249A CN110045038B CN 110045038 B CN110045038 B CN 110045038B CN 201910394249 A CN201910394249 A CN 201910394249A CN 110045038 B CN110045038 B CN 110045038B
- Authority
- CN
- China
- Prior art keywords
- impurity
- atorvastatin
- impurities
- solution
- mobile phase
- 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
- G01N30/04—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
- G01N30/26—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
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- 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)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention belongs to the field of analytical chemistry, and particularly relates to a method for separating and determining atorvastatin and related impurities by using an HPLC (high performance liquid chromatography) method. The chromatographic column adopted by the method takes octadecylsilane chemically bonded silica as a filler, and adopts a mobile phase consisting of an inorganic salt buffer system and an organic solvent for gradient elution, and the mobile phase enters a detector for detection; the related impurities are one or more of impurities A, B, C, D, E, F, G and H. The method can effectively separate the atorvastatin and related impurities (impurities A to G), has good separation degree, strong specificity and high and accurate sensitivity, and has extremely important significance for realizing the quality control of the atorvastatin.
Description
Technical Field
The invention belongs to the field of analytical chemistry, and particularly relates to a method for separating and determining atorvastatin and related impurities by using an HPLC (high performance liquid chromatography) method.
Background
Acrivastine (Acrivastine), chemical name (E) -6- [ (E) -3- (1-pyrrolidinyl) -1-p-methylphenylpropenyl ] -2-pyridineacrylic acid, molecular formula as follows:
C22H24N2O2 348.44
(E) -6- [ (E) -3- (1-pyrrolidinyl) -1-p-methylphenylpropenyl ] -2-pyridineacrylic acid
Alvastigmine was originally developed as a new generation of antihistamines by Kurarin Schker, and was first marketed in the United kingdom in 1988Is named as
Is a strong competitive histamine H1 receptor antagonist and has no obvious anticholinergic effect. Has low penetration ability to the central nervous system. Avastin is suitable for relieving allergic rhinitis, including disease symptoms of hay fever, chronic spontaneous urticaria, skin scratch disease, cholinergic urticaria and idiopathic acquired cold urticaria.
Strict control is required for impurities generated in the process of preparing the atorvastatin or related substances introduced in the raw material medicaments or preparations. However, at present, the bulk drugs of the atorvastatin are not recorded in the national pharmacopoeia 2015 edition, the European pharmacopoeia 9.6 edition and the United states pharmacopoeia 41 edition, and a method for quickly and simultaneously separating various impurities of the atorvastatin is not disclosed and reported. Therefore, the method for simultaneously separating and determining the avastin and the impurities thereof is very important for realizing the quality control of the avastin.
In view of the above, the invention self-establishes a set of high performance liquid chromatography for separating the atorvastatin and the related impurities. The method has the advantages of simplicity, rapidness, high accuracy and the like, can realize effective separation of the atorvastatin and the impurity A, B, C, D, E, F, G, H thereof, has good specificity, is not interfered by blank and other impurities, can elute related impurities with small polarity in a sample, has the separation degree between impurity peaks larger than 1.5, and meets the requirements of related substances. Has instructive significance for the quality research of the medicine.
Disclosure of Invention
The invention aims to provide a method for separating and determining the atorvastatin and related impurities by using an HPLC method. The technical scheme is as follows:
a method for separating and determining atorvastatin and related impurities by an HPLC method comprises the steps of adopting a chromatographic column with octadecylsilane chemically bonded silica as a filler, carrying out gradient elution by taking an inorganic salt buffer system as a mobile phase A and an organic solvent as a mobile phase B, and detecting the elution by a detector, wherein the impurities comprise one or more of impurities A, impurities B, impurities C, impurities D, impurities E, impurities F, impurities G and impurities H, and the specific structural formula is as follows:
the specific information on the impurities is shown in the following table:
further, the inorganic salt buffer system is an acetate buffer system.
Further, the acetate is ammonium acetate, and the molar concentration of the ammonium acetate is 0.015-0.025 mol/L.
Preferably, the molar concentration of the ammonium acetate is 0.02 mol/L.
Further, the organic solvent is one or more of acetonitrile, ethanol and methanol.
Preferably, the organic solvent is acetonitrile.
Further, the gradient elution conditions were as follows:
0-5min, wherein the volume ratio of the mobile phase A to the mobile phase B is as follows: 83: 17;
35min, the volume ratio of the mobile phase A to the mobile phase B is as follows: 70: 30, of a nitrogen-containing gas;
40-63min, wherein the volume ratio of the mobile phase A to the mobile phase B is as follows: 20: 80;
63.1-70min, the volume ratio of the mobile phase A to the mobile phase B is as follows: 83: 17.
further, the particle size of the filler particles of the chromatographic column is 3-5 μm; the temperature of the chromatographic column is 25-35 ℃; the flow rate of the mobile phase is 0.5-1.5 ml/min; the detection wavelength of the detector is 250nm +/-2 nm.
Preferably, the particle size of the filler particles of the chromatographic column is 5 μm; the column temperature of the chromatographic column is 30 ℃; the flow rate of the mobile phase is 1.0 ml/min; the detection wavelength of the detector is 250 nm.
The second purpose of the invention is to provide a specific detection step for separating and measuring the atorvastatin and related impurities by the HPLC method. The technical scheme is as follows
The specific steps for separating and measuring the avastin and related impurities are as follows:
1) preparing a sample solution: taking a proper amount of an atorvastatin sample, adding a diluent to dissolve and dilute the atorvastatin sample into a solution containing 0.3mg of the atorvastatin in each 1ml of the atorvastatin sample, and shaking up to obtain a sample solution;
2) preparing a control solution: precisely measuring a proper amount of the sample solution in the step 1), diluting the sample solution with a diluent to prepare a solution containing 0.6 mu g of the sample solution in each 1ml, and shaking up to be used as a control solution;
3) respectively sampling the sample solution obtained in the step 1) and the control solution obtained in the step 2), carrying out high performance liquid chromatography analysis, recording a chromatogram, determining the retention time of the atorvastatin and related impurities, and calculating the content of the atorvastatin related impurities in the sample solution according to a self-control method of a correction factor.
Further, the diluent is acetonitrile water solution with the volume percentage concentration of 10-30%.
Preferably, the diluent is 20% acetonitrile in water by volume.
The third purpose of the invention is to provide a reagent composition for separating and determining the atorvastatin and related impurities. The technical scheme is as follows:
the reagent composition for determining the atorvastatin and related impurities through solid-liquid separation adopts octadecylsilane chemically bonded silica as a stationary phase, acetic acid buffer salt as a reagent A and one or more of acetonitrile, ethanol and methanol as a reagent B, wherein the impurities comprise one or more of impurities A, B, C, D, E, F, G and H, and the specific structure is as follows:
further, the acetate is ammonium acetate, and the molar concentration of the ammonium acetate is 0.015-0.025 mol/L.
The invention has the beneficial effects that:
1) the invention provides a method for separating and measuring atorvastatin and related impurities by using an HPLC (high performance liquid chromatography) method, which realizes effective separation of atorvastatin and impurities A, B, C, D, E, F, G and H thereof, has good specificity, is not interfered by blank and other impurities, has the separation degree between a main peak and each impurity peak being more than 1.5, and meets the requirements of related substances.
2) The method is simple, has strong specificity and high sensitivity and accuracy, and can effectively ensure the quality of the atorvastatin.
3) The reagent composition for measuring the atorvastatin and the related impurities through solid-liquid separation can effectively separate the atorvastatin and the related impurities, and has extremely important significance for realizing the quality control of the atorvastatin.
Drawings
FIG. 1 blank solvent positioning HPLC plot.
FIG. 2 localized HPLC profile of impurity A.
FIG. 3 localized HPLC profile of impurity B.
FIG. 4 localized HPLC profile of impurity C.
FIG. 5 localized HPLC profile of impurity D.
FIG. 6 localized HPLC profile of impurity E.
FIG. 7 localized HPLC profile of impurity F.
FIG. 8 localized HPLC profile of impurity G.
FIG. 9 localized HPLC profile of impurity H.
Figure 10 atorvastatin localization HPLC profile.
FIG. 11 HPLC chart of mixed solution.
Detailed Description
Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The experimental methods of the preferred embodiments, which do not indicate specific conditions, are generally performed according to conventional conditions, and the examples are given for better illustration of the present invention, but the present invention is not limited to the examples. Therefore, those skilled in the art should make insubstantial modifications and adaptations to the embodiments of the present invention in light of the above teachings and remain within the scope of the invention.
Example 1
1. Chromatographic conditions
A chromatographic column: octadecylsilane chemically bonded silica gel as filler (VP-ODS 4.6X 250mm, 5 μm or equivalent performance column)
Detection wavelength: flow rate at 250 nm: 1.0ml/min
Sample introduction amount: 20 μ l column temperature: 30 deg.C
Mobile phase A: ammonium acetate solution (0.02mol/L)
Mobile phase B: acetonitrile
Diluent agent: 20% acetonitrile Water
Gradient elution conditions:
2. chromatogram of avastin and related impurities
Preparing an impurity A-H positioning solution: respectively taking about 10mg of the impurity A-H reference substance, placing the reference substance into a 100ml measuring flask, adding a diluent to dissolve and dilute the reference substance to a scale, and shaking up to obtain the impurity A-H stock solution. Precisely transferring 1ml of each solution, putting the solution into a 10ml measuring flask, adding a diluent to dilute the solution to a scale, and shaking up to obtain the positioning solution of the impurities A-H.
Preparing a mixed solution: precisely transferring 0.75ml of each of the impurity A, the impurity B, the impurity C, the impurity D, the impurity E, the impurity F, the impurity G stock solution and the impurity H stock solution into a 50ml measuring flask filled with about 15mg of a test sample, adding a diluent to dissolve and dilute the solution to a scale, and shaking up to obtain the test sample.
And (3) respectively sampling the diluent, the impurity positioning solutions and the mixed solution according to the chromatographic conditions, recording a chromatogram, and determining results shown in the following table. The results are shown in FIGS. 1 to 11.
3. Results of the experiment
Example 2
1. Chromatographic conditions
A chromatographic column: octadecylsilane chemically bonded silica gel as filler (VP-ODS 4.6X 250mm, 5 μm or equivalent performance column)
Detection wavelength: flow rate at 250 nm: 0.5ml/min
Sample introduction amount: 20 μ l column temperature: 25 deg.C
Mobile phase A: ammonium acetate solution (0.015mol/L)
Mobile phase B: acetonitrile
Diluent agent: 10% acetonitrile Water
Gradient elution conditions:
2. sample and control solutions were prepared and tested according to the method and procedure of step 2) in example 1.
3. Results of the experiment
The avastin, the impurity A, the impurity B, the impurity C, the impurity D, the impurity E, the impurity F, the impurity G and the impurity H can be effectively separated without being interfered by blank and other impurities, and the separation degrees between the main peak and each impurity peak are more than 1.5, so that the requirement of related substances is met.
Example 3
1. Chromatographic conditions
A chromatographic column: octadecylsilane chemically bonded silica gel as filler (VP-ODS 4.6X 250mm, 5 μm or equivalent performance column)
Detection wavelength: flow rate at 252 nm: 1.0ml/min
Sample introduction amount: 20 μ l column temperature: 30 deg.C
Mobile phase A: ammonium acetate solution (0.02mol/L)
Mobile phase B: acetonitrile
Diluent agent: 20% acetonitrile Water
Gradient elution conditions:
2. sample and control solutions were prepared and tested according to the method and procedure of step 2) in example 1.
3. Results of the experiment
The avastin, the impurity A, the impurity B, the impurity C, the impurity D, the impurity E, the impurity F, the impurity G and the impurity H can be effectively separated without being interfered by blank and other impurities, and the separation degrees between the main peak and each impurity peak are more than 1.5, so that the requirement of related substances is met.
Example 4
1. Chromatographic conditions
A chromatographic column: octadecylsilane chemically bonded silica gel as filler (VP-ODS 4.6X 250mm, 3 μm or equivalent performance column)
Detection wavelength: flow rate at 248 nm: 1.5ml/min
Sample introduction amount: 20 μ l column temperature: 30 deg.C
Mobile phase A: ammonium acetate solution (0.015mol/L)
Mobile phase B: acetonitrile
Diluent agent: 20% acetonitrile Water
Gradient elution conditions:
2. sample and control solutions were prepared and tested according to the method and procedure of step 2) in example 1.
3. Results of the experiment
The avastin, the impurity A, the impurity B, the impurity C, the impurity D, the impurity E, the impurity F, the impurity G and the impurity H can be effectively separated without being interfered by blank and other impurities, and the separation degrees between the main peak and each impurity peak are more than 1.5, so that the requirement of related substances is met.
Example 5
1. Chromatographic conditions
A chromatographic column: octadecylsilane chemically bonded silica gel as filler (VP-ODS 4.6X 250mm, 3 μm or equivalent performance column)
Detection wavelength: flow rate at 250 nm: 1.0ml/min
Sample introduction amount: 20 μ l column temperature: 35 deg.C
Mobile phase A: ammonium acetate solution (0.025mol/L)
Mobile phase B: acetonitrile
Diluent agent: 30% acetonitrile Water
Gradient elution conditions:
2. sample and control solutions were prepared and tested according to the method and procedure of step 2) in example 1.
3. Results of the experiment
The avastin, the impurity A, the impurity B, the impurity C, the impurity D, the impurity E, the impurity F, the impurity G and the impurity H can be effectively separated without being interfered by blank and other impurities, and the separation degrees between the main peak and each impurity peak are more than 1.5, so that the requirement of related substances is met.
Comparative example 1
In this comparative example, the conditions were the same as in example 1 except that the mobile phase gradient elution procedure was inconsistent.
Gradient elution conditions:
the experimental results are as follows: the impurity under this condition is less separated from the main peak than in example 1, and impurity F remains less.
Finally, the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting, although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all of them should be covered in the claims of the present invention.
Claims (4)
1. A method for separating and determining atorvastatin and related impurities by an HPLC method is characterized in that a chromatographic column with octadecylsilane chemically bonded silica as a filler is adopted, an inorganic salt buffer system is used as a mobile phase A, an organic solvent is used as a mobile phase B for gradient elution, and the gradient elution enters a detector for detection, wherein the impurities comprise an impurity A, an impurity B, an impurity E, an impurity C, an impurity D, an impurity F, an impurity G and an impurity H, and the specific structural formula is as follows:
the inorganic salt buffer system is ammonium acetate, and the molar concentration of the ammonium acetate is 0.015-0.025 mol/L; the organic solvent is acetonitrile;
the gradient elution conditions were as follows:
the detection wavelength of the detector is 250nm +/-2 nm.
2. The method of claim 1, wherein the packing particles of the chromatography column have a particle size of 3-5 μ ι η; the temperature of the chromatographic column is 25-35 ℃; the flow rate of the mobile phase is 0.5-1.5 ml/min.
3. The method according to any one of claims 1-2, wherein the specific separation assay steps are as follows:
1) preparing a sample solution: taking an atorvastatin sample, adding a diluent to dissolve and diluting the atorvastatin sample to prepare a solution containing 0.3mg of the atorvastatin in each 1ml of the sample solution;
2) preparing a control solution: precisely measuring a proper amount of the sample solution in the step 1), diluting the sample solution with a diluent to prepare a solution containing 0.6 mu g of the sample solution in each 1ml, and shaking up to be used as a control solution;
3) respectively sampling the sample solution obtained in the step 1) and the control solution obtained in the step 2), carrying out high performance liquid chromatography analysis, recording a chromatogram, determining the retention time of the atorvastatin and related impurities, and calculating the content of the atorvastatin related impurities in the sample solution according to a self-control method of a correction factor.
4. The method of claim 3, wherein the diluent is an aqueous acetonitrile solution having a concentration of 10-30% by volume.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910394249.8A CN110045038B (en) | 2019-05-13 | 2019-05-13 | Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910394249.8A CN110045038B (en) | 2019-05-13 | 2019-05-13 | Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110045038A CN110045038A (en) | 2019-07-23 |
| CN110045038B true CN110045038B (en) | 2021-12-14 |
Family
ID=67281571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910394249.8A Active CN110045038B (en) | 2019-05-13 | 2019-05-13 | Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110045038B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113933401B (en) * | 2020-06-29 | 2023-07-21 | 重庆华邦制药有限公司 | Separation detection of atorvastatin intermediate Z 3 Method for the neutralization of genotoxic impurities |
| CN113024451A (en) * | 2021-02-26 | 2021-06-25 | 重庆医药高等专科学校 | Avastine photodegradation impurity and application and preparation method thereof |
| CN114280174B (en) * | 2021-12-07 | 2023-12-29 | 嘉实（湖南）医药科技有限公司 | Detection method of avanafil and related impurities thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4501893A (en) * | 1982-02-04 | 1985-02-26 | Findlay John W A | 3-{6-[3-Pyrrolidino-1-(4-tolyl)prop-1-enyl]-2-pyridyl}acrylic acid and pharmaceutically acceptable salts thereof |
| CN101838234A (en) * | 2009-06-17 | 2010-09-22 | 重庆华邦制药股份有限公司 | Synthesis method of alpha ethyl ester derivative |
| CN102311381A (en) * | 2010-07-06 | 2012-01-11 | 重庆华邦胜凯制药有限公司 | Method for synthesizing alpha ethyl ester derivative |
| CN104447516A (en) * | 2014-12-15 | 2015-03-25 | 重庆华邦制药有限公司 | Preparation method of acrivastine |
| CN104931599A (en) * | 2015-04-15 | 2015-09-23 | 北京嘉林药业股份有限公司 | Determining method of atorvastatin calcium related substance |
| CN109254097A (en) * | 2018-11-13 | 2019-01-22 | 重庆华邦胜凯制药有限公司 | The method of Z3 and relative substance in a kind of high performance liquid chromatography separation analysis Acrivastine bulk pharmaceutical chemicals intermediate Z3 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7973055B2 (en) * | 2006-03-09 | 2011-07-05 | Theravance, Inc. | Crystalline forms of a biphenyl compound |
-
2019
- 2019-05-13 CN CN201910394249.8A patent/CN110045038B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4501893A (en) * | 1982-02-04 | 1985-02-26 | Findlay John W A | 3-{6-[3-Pyrrolidino-1-(4-tolyl)prop-1-enyl]-2-pyridyl}acrylic acid and pharmaceutically acceptable salts thereof |
| CN101838234A (en) * | 2009-06-17 | 2010-09-22 | 重庆华邦制药股份有限公司 | Synthesis method of alpha ethyl ester derivative |
| CN102311381A (en) * | 2010-07-06 | 2012-01-11 | 重庆华邦胜凯制药有限公司 | Method for synthesizing alpha ethyl ester derivative |
| CN104447516A (en) * | 2014-12-15 | 2015-03-25 | 重庆华邦制药有限公司 | Preparation method of acrivastine |
| CN104931599A (en) * | 2015-04-15 | 2015-09-23 | 北京嘉林药业股份有限公司 | Determining method of atorvastatin calcium related substance |
| CN109254097A (en) * | 2018-11-13 | 2019-01-22 | 重庆华邦胜凯制药有限公司 | The method of Z3 and relative substance in a kind of high performance liquid chromatography separation analysis Acrivastine bulk pharmaceutical chemicals intermediate Z3 |
Non-Patent Citations (2)
| Title |
|---|
| Identification, synthesis and structural characterization of process related and degradation impurities of acrivastine and validation of HPLC method;Ajay 等;《Journal of Pharmaceutical and Biomedical Analysis》;20170130;第133卷;第12-26页 * |
| 阿伐斯汀胶囊人体药动学和生物等效性;周远大 等;《中国新药与临床杂志》;20070430;第26卷(第04期);第249-252页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110045038A (en) | 2019-07-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110045038B (en) | Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method | |
| CN108593831B (en) | HPLC detection method of fasudil hydrochloride related substances | |
| CN109254097B (en) | Method for separating and analyzing Z3 and related impurities in intermediate Z3 of bulk drug of atorvastatin through high performance liquid chromatography | |
| CN106146332B (en) | Method for separating and determining linezolid raw material X3 and process impurity X2 thereof | |
| CN107831230A (en) | The method of related impurities in separation determination Acrivastine and its preparation | |
| CN111024831B (en) | Method for separating moxifloxacin hydrochloride and impurities thereof by high performance liquid chromatography | |
| CN107782832B (en) | Method for separating and determining bepotastine besilate and potential genotoxic impurities thereof by HPLC (high performance liquid chromatography) | |
| CN103353492A (en) | Method of separating and measuring solifenacin succinate raw material and preparation thereof by using liquid chromatography | |
| CN107525877B (en) | Method for separating and determining brexpiprazole and impurities thereof by adopting liquid chromatography | |
| CN110865130B (en) | Olopatadine hydrochloride and detection method of related substances thereof | |
| CN116908347A (en) | Method for detecting bacteriostatic agent and flavoring agent of amisulpride oral solution | |
| CN109030653B (en) | Detection method of related substances in levofolinic acid | |
| CN110954629A (en) | Control method for measuring content of furfuryl amine in furosemide | |
| CN104764840B (en) | The separation of palonosetron Hcl and impurity and detection method | |
| CN114324642B (en) | Method for determining dextromethorphan hydrobromide related substances | |
| CN114354810A (en) | Method for detecting impurity N in clindamycin phosphate and method for separating impurity | |
| CN110412164B (en) | Method for detecting related substances of mexiletine hydrochloride | |
| CN114280191A (en) | Method for detecting related substances in bis-cysteine and preparation thereof | |
| CN108226340B (en) | Method for separating and measuring diflucortolone and 6 beta diflucortolone and 16 beta diflucortolone thereof | |
| CN113820417A (en) | Method for separating and measuring piroxicam and impurities thereof | |
| CN108181419B (en) | Detection method of diethyl naphthalene cholamine raw material or preparation related substances thereof | |
| CN108061765B (en) | Separation and determination of erlotinib hydrochloride intermediate M by HPLC method1And related impurities | |
| CN107860838B (en) | Method for separating and measuring Retapamulin and related substances by HP L C method | |
| CN107305199B (en) | Method for separating and measuring two components and related substances in compound nasal spray of azelastine hydrochloride and fluticasone propionate | |
| CN107656005B (en) | Method for separating and determining erlotinib hydrochloride and potential impurities |
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 |