CN111879868A - Method for determining related substances of valacyclovir hydrochloride - Google Patents
Method for determining related substances of valacyclovir hydrochloride Download PDFInfo
- Publication number
- CN111879868A CN111879868A CN202010617412.5A CN202010617412A CN111879868A CN 111879868 A CN111879868 A CN 111879868A CN 202010617412 A CN202010617412 A CN 202010617412A CN 111879868 A CN111879868 A CN 111879868A
- Authority
- CN
- China
- Prior art keywords
- solution
- mobile phase
- impurity
- methanol
- related substances
- 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.)
- Pending
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
- G01N30/30—Control of physical parameters of the fluid carrier of temperature
-
- 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
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
-
- 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
- G01N30/60—Construction of the column
-
- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
- G01N2030/324—Control of physical parameters of the fluid carrier of pressure or speed speed, flow rate
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)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a method for determining related substances of valacyclovir hydrochloride. The invention adopts a high performance liquid chromatography to measure related substances, and the chromatographic conditions are as follows: a chromatographic column: a C18 chromatography column; flow rate: 0.5-1.5 ml/min; detection wavelength: 200-300 nm; column temperature: 20-40 ℃; mobile phase A: potassium dihydrogen phosphate solution-methanol; mobile phase B: trifluoroacetic acid-methanol; and (3) an elution mode: gradient elution; preparing a sample solution from a sample to be detected by using a diluent. Compared with the original liquid chromatography, the method is simple and convenient in detection, and can detect other impurities which can be detected by multiple detection methods originally in the same chromatographic system, so that the working efficiency is improved; compared with the original measuring method, the method is simpler, more convenient and more economical, and has high accuracy and good precision.
Description
Technical Field
The invention belongs to the technical field of medicine quality detection, and particularly relates to a method for determining related substances of valacyclovir hydrochloride.
Background
Valacyclovir hydrochloride is a prodrug of acyclovir, is marketed in the United kingdom and Ireland in 1 month of 1995 and is approved by FDA in 6 months of the same year, and compared with the acyclovir, the bioavailability of the valacyclovir is 3-5 times higher than that of the acyclovir, and the curative effect is further improved. The virus killing agent is mainly used for infectious diseases with high morbidity, high harmfulness and high mortality caused by viruses. For example, acute and chronic hepatitis caused by hepatitis virus, eye, brain, mouth, lip and genital infection caused by herpes virus, tracheitis, pneumonia, measles, mumps and poliomyelitis caused by respiratory virus, acute enteritis diarrhea caused by enterovirus, global or local influenza pandemics caused by influenza virus, hemorrhagic fever and dengue fever caused by various viruses, and the like.
At present, the detection method of related substances of valacyclovir hydrochloride is high performance liquid chromatography carried in Chinese pharmacopoeia, and only acyclovir is used as a known impurity for research.
Disclosure of Invention
The invention aims to provide a method for measuring related substances of valacyclovir hydrochloride. Compared with the original liquid chromatography, the method is simple and convenient in detection, and can detect other impurities which can be detected by multiple detection methods originally in the same chromatographic system, so that the working efficiency is improved; compared with the original measuring method, the method is simpler, more convenient and more economical, and has high accuracy and good precision.
The method for determining related substances of valacyclovir hydrochloride comprises the following steps: the related substances are measured by adopting a high performance liquid chromatography, and the chromatographic conditions are as follows: a chromatographic column: a C18 chromatography column; flow rate: 0.5-1.5 ml/min; detection wavelength: 200-300 nm; column temperature: 20-40 ℃; mobile phase A: potassium dihydrogen phosphate solution-methanol; mobile phase B: trifluoroacetic acid-methanol; and (3) an elution mode: gradient elution; preparing a sample solution from a sample to be detected by using a diluent.
The chromatographic column is Ultimate XB-C18, 250 multiplied by 4.6mm, 5 μm.
The mobile phase A is a mixed solution of potassium dihydrogen phosphate solution and methanol with the volume ratio of 85:15, the concentration of the potassium dihydrogen phosphate solution is 0.01mol/L, and the pH value is adjusted to 3.0 by using phosphoric acid.
The mobile phase B is a mixed solution of trifluoroacetic acid and methanol with the volume ratio of 0.5: 100.
The flow rate was 1.0 ml/min.
The column temperature was 35 ℃.
The detection wavelength is 251 nm.
The diluent is 0.01mol/L potassium dihydrogen phosphate solution, and the pH value is adjusted to 3.0 by phosphoric acid.
The gradient elution is: the mobile phase a was first flushed for 8min and then the volume ratio of mobile phase a and mobile phase B was changed to 35:65 over an 18min linear gradient, held to 6 times the retention time of the main peak.
The method for determining related substances of valacyclovir hydrochloride has good specificity and high accuracy, can effectively separate a main peak from each impurity peak, can accurately detect the content of each impurity, and has good promotion effect on quality control and establishment of a unified standard for the product.
Drawings
Figure 1, valacyclovir localization solution profile.
FIG. 2, impurity A solution map.
FIG. 3, impurity B solution profile.
Fig. 4, impurity C solution profile.
FIG. 5, System suitability solution map.
FIG. 6, valacyclovir hydrochloride test solution chromatogram.
Figure 7, linear and range operating plots for valacyclovir.
Figure 8, impurity a linear and range operating plots.
Figure 9, impurity B linear and range operating plots.
Figure 10, impurity C linear and range operating plots.
Detailed Description
Test solution: taking 50mg of the product, accurately weighing, placing in a 100ml measuring flask, adding a diluent to dissolve and dilute to a scale, and shaking up to obtain a test solution.
Control solution: precisely measuring the sample solution lml, placing the sample solution lml into a 200ml measuring flask, diluting the sample solution lml to a scale with a diluent, and shaking up to be used as a control solution.
Acyclovir (impurity B) control stock solution: taking another acyclovir reference substance of about 13mg, precisely weighing, putting into a 50ml measuring flask, adding 2ml of 0.lmol/L sodium hydroxide solution to dissolve, diluting with water to scale, and shaking up to obtain acyclovir reference substance storage solution.
Acyclovir (impurity B) localization solution: accurately measuring 5ml of acyclovir reference substance stock solution, placing the acyclovir reference substance stock solution into a 20ml measuring flask, diluting the acyclovir reference substance stock solution to a scale with a diluent, and shaking up to obtain the acyclovir reference substance.
Acyclovir (impurity B) control solution: accurately measuring 5ml of acyclovir reference product stock solution, placing the acyclovir reference product stock solution into a 200ml measuring flask, diluting the acyclovir reference product stock solution to a scale by using a diluent, and shaking up to obtain acyclovir reference product solution.
Valacyclovir reference stock solution: valacyclovir hydrochloride reference substance of about 11.3mg (about equivalent to valacyclovir 10mg) is precisely weighed, placed in a 100ml measuring bottle, dissolved by adding a diluent and diluted to a scale, and used as a valacyclovir reference substance stock solution.
Valacyclovir positioning solution: and precisely measuring 5ml of valacyclovir reference product stock solution, putting the valacyclovir reference product stock solution into a 20ml measuring flask, diluting the valacyclovir reference product stock solution to a scale by using a diluent, and shaking up the valacyclovir reference product stock solution to obtain the valacyclovir reference product.
Impurity a control stock solution: precisely weighing about 10mg of impurity A reference substance, placing into a 100ml measuring flask, adding 10ml of 0.1mol/L sodium hydroxide solution to dissolve, adding 10ml of 0.1% phosphoric acid solution, diluting with water to scale, and collecting the reference substance as impurity A reference substance stock solution.
Impurity a localization solution: precisely measuring 1ml of impurity A reference substance stock solution, placing into a 10ml measuring flask, diluting with diluent to scale, and shaking.
Impurity C control stock solution: precisely weighing about 11.25mg (about equivalent to the impurity C10mg) of impurity C hydrochloride reference substance, placing into a 100ml measuring flask, adding a diluent to dissolve and dilute to scale, shaking up to obtain impurity C reference substance stock solution;
impurity C localization solution: precisely measuring 1ml of impurity C reference substance stock solution, placing the stock solution in a 10ml measuring flask, diluting the stock solution to a scale with a diluent, and shaking up to obtain an impurity C positioning solution.
System applicability solution: precisely measuring 5ml of valacyclovir reference product storage solution and 5ml of acyclovir reference product storage solution respectively, 2ml of impurity A reference product storage solution and 2ml of impurity C reference product storage solution respectively, putting the samples into the same 50ml measuring flask, adding a diluent to dissolve and dilute the samples to scale, and shaking up the samples to obtain system applicability solutions.
Respectively and precisely measuring 20 mul of each of the test solution, the acyclovir reference solution, the reference solution, each impurity positioning solution and the system applicability solution, respectively injecting into a liquid chromatograph, and recording the chromatogram until the retention time of valacyclovir peak is 6 times.
Limitation: if an impurity peak exists in a chromatogram of a test solution, calculating the content of acyclovir by the peak area according to an external standard method to be 1.3 percent; impurity a (relative retention time of about 0.6) should not be greater than 0.4 times (0.2%) the major peak area of the control solution, impurity C (relative retention time of about 1.1) should not be greater than 0.4 times (0.2%) the major peak area of the control solution, other impurities should not be greater than 0.2 times (0.1%) the major peak area of the control solution, and the sum of the peak areas of the other impurities should not be greater than 0.8 times (0.4%) the major peak area of the control solution.
1.1 specificity
The peaks in the solution with system applicability are completely separated, the separation degree of the impurity A and the impurity B is 7.50, the separation degree of the impurity B and valaciclovir is 6.10, the separation degree of the valaciclovir and the impurity C is 26.91, the theoretical plate number of the valaciclovir is 4582, and the separation effect and the column efficiency are good. The HPLC chromatogram is shown in figures 1-6.
1.2 limit of quantitation
Taking valacyclovir reference substance stock solution, impurity A reference substance stock solution, acyclovir (impurity B) reference substance stock solution and impurity C reference substance stock solution, gradually diluting, and taking the obtained solution as a quantitative limit solution when the signal-to-noise ratio (S/N) is about 10. Taking the quantitative limit concentration solution, continuously injecting 6 needles, and calculating the Relative Standard Deviation (RSD) of the peak area and retention time of each component. The results are shown in Table 1.
TABLE 1 results of quantitative limit tests on related substances (impurity A, B, C and valacyclovir hydrochloride)
| Name (R) | Impurity A | Impurity B | Impurity C | Valaciclovir |
| Quantitative limit (ng) | 0.6 | 0.8 | 1.2 | 1.6 |
| Quantitative limit concentration (mu g/ml) | 0.03 | 0.04 | 0.06 | 0.08 |
| About equivalent to the test solution (%) | 0.006 | 0.008 | 0.012 | 0.016 |
1.3 Linearity and Range
Accurately measuring valacyclovir reference substance storage solution, impurity A reference substance storage solution, acyclovir (impurity B) reference substance storage solution and impurity C reference substance storage solution by 0.2ml, 0.5ml, 1ml, 2ml, 3ml and 5ml respectively, placing in a 100ml measuring flask, diluting to scale with diluent, and shaking to obtain linear solutions 2#, 3#, 4#, 5#, 6#, and 7 #. The quantitative limiting solution is used as the linear solution 1 #.
Precisely measuring 20 μ l of each of the linear solutions 1# to 7# and injecting the linear solutions into a liquid chromatograph, and recording a chromatogram. The results of linear regression of the peak areas (A) with the concentrations (C) are shown in tables 2-5 and the linear curves are shown in FIGS. 7-10. The results show that: the valaciclovir has a good linear relation in the concentration range of 0.08-5.10 mug/ml; the impurity A has a good linear relation within the concentration range of 0.03-5.05 mu g/ml; the impurity B is in the concentration range of 0.04-13.10 mu g/ml, and the linear relation is good; the impurity C has a good linear relation within the concentration range of 0.06-4.95 mu g/ml.
TABLE 2 valacyclovir hydrochloride linearity and Range test results
TABLE 3 Linear and Range test results for impurity A
TABLE 4 impurity B linearity and Range test results
TABLE 5 impurity C Linear and Range test results
1.4 repeatability
Test solution: precisely weighing 50mg of the product, placing into a 100ml measuring flask, adding a diluent to dissolve and dilute to scale, and shaking up to obtain the product. 6 parts of test solution is prepared by the same method. The results of the measurements according to the method and the calculation according to the area normalization method are shown in Table 6.
TABLE 6 repeatability test results for related substances (impurity A, B, C)
From the results it can be seen that: the method has good repeatability.
1.5 intermediate precision
Test solution: precisely weighing 50mg of the product, placing into a 100ml measuring flask, adding a diluent to dissolve and dilute to scale, and shaking up to obtain the product.
The test solutions are prepared by 6 parts by the same method, different chromatographs are adopted by different experimenters on different dates, the measurement is carried out according to the method, the calculation is carried out according to the area normalization method, and the results are shown in the table 7.
TABLE 7 results of intermediate precision test on related substance (impurity A, B, C)
From the results it can be seen that: the method has good intermediate precision.
The chromatographic conditions in each of the above tests were: a chromatographic column: ultimate XB-C18, 250X 4.6mm, 5 μm; flow rate: 1 ml/min; detection wavelength: 251 nm; column temperature: 35 ℃; preparing a sample solution from a sample to be detected by using a diluent; the mobile phase A is a mixed solution of potassium dihydrogen phosphate solution and methanol with the volume ratio of 85:15, the concentration of the potassium dihydrogen phosphate solution is 0.01mol/L, and the pH value is adjusted to 3.0 by phosphoric acid; the mobile phase B is a mixed solution of trifluoroacetic acid and methanol with the volume ratio of 0.5: 100; the diluent is 0.01mol/L potassium dihydrogen phosphate solution, and the pH value is adjusted to 3.0 by phosphoric acid; gradient elution: the mobile phase a was first flushed for 8min and then the volume ratio of mobile phase a and mobile phase B was changed to 35:65 over an 18min linear gradient, held to 6 times the retention time of the main peak.
Claims (9)
1. A method for measuring related substances of valacyclovir hydrochloride is characterized in that the related substances are measured by a high performance liquid chromatography, and the chromatographic conditions are as follows: a chromatographic column: a C18 chromatography column; flow rate: 0.5-1.5 ml/min; detection wavelength: 200-300 nm; column temperature: 20-40 ℃; mobile phase A: potassium dihydrogen phosphate solution-methanol; mobile phase B: trifluoroacetic acid-methanol; and (3) an elution mode: gradient elution; preparing a sample solution from a sample to be detected by using a diluent.
2. The method of claim 1, wherein the chromatographic column is Ultimate XB-C18, 250 x 4.6mm, 5 μm.
3. The method of claim 1, wherein the mobile phase A is a mixed solution of potassium dihydrogen phosphate and methanol at a volume ratio of 85:15, the concentration of the potassium dihydrogen phosphate solution is 0.01mol/L, and the pH value is adjusted to 3.0 with phosphoric acid.
4. The method of claim 1, wherein the mobile phase B is a mixed solution of trifluoroacetic acid and methanol at a volume ratio of 0.5: 100.
5. The method of claim 1 wherein the flow rate is 1.0 ml/min.
6. The method of claim 1 wherein the column temperature is 35 ℃.
7. The method of claim 1 wherein the detection wavelength is 251 nm.
8. The method of claim 1 wherein the diluent is 0.01mol/L potassium dihydrogen phosphate solution, and the pH is adjusted to 3.0 with phosphoric acid.
9. The method of determining a valacyclovir hydrochloride related substance as claimed in claim 1 wherein the gradient elution is: the mobile phase a was first flushed for 8min and then the volume ratio of mobile phase a and mobile phase B was changed to 35:65 over an 18min linear gradient, held to 6 times the retention time of the main peak.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010617412.5A CN111879868A (en) | 2020-06-30 | 2020-06-30 | Method for determining related substances of valacyclovir hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010617412.5A CN111879868A (en) | 2020-06-30 | 2020-06-30 | Method for determining related substances of valacyclovir hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111879868A true CN111879868A (en) | 2020-11-03 |
Family
ID=73157600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010617412.5A Pending CN111879868A (en) | 2020-06-30 | 2020-06-30 | Method for determining related substances of valacyclovir hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111879868A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115745997A (en) * | 2022-11-30 | 2023-03-07 | 湖北省宏源药业科技股份有限公司 | Preparation method of high-purity valaciclovir impurity H |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060084668A1 (en) * | 2004-09-04 | 2006-04-20 | Amihai Eisenstadt | Isolated valacyclovir impurity, process for the preparation of valacyclovir impurity and use as a reference standard |
| CN104188928A (en) * | 2014-09-17 | 2014-12-10 | 山东新时代药业有限公司 | Valaciclovir hydrochloride tablet and preparation method thereof |
| CN110940754A (en) * | 2019-12-18 | 2020-03-31 | 湖北省宏源药业科技股份有限公司 | High performance liquid chromatography method for separating and measuring impurities in valacyclovir hydrochloride |
-
2020
- 2020-06-30 CN CN202010617412.5A patent/CN111879868A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060084668A1 (en) * | 2004-09-04 | 2006-04-20 | Amihai Eisenstadt | Isolated valacyclovir impurity, process for the preparation of valacyclovir impurity and use as a reference standard |
| CN104188928A (en) * | 2014-09-17 | 2014-12-10 | 山东新时代药业有限公司 | Valaciclovir hydrochloride tablet and preparation method thereof |
| CN110940754A (en) * | 2019-12-18 | 2020-03-31 | 湖北省宏源药业科技股份有限公司 | High performance liquid chromatography method for separating and measuring impurities in valacyclovir hydrochloride |
Non-Patent Citations (3)
| Title |
|---|
| GIRIJA B.BHAVAR 等: "Development and validation of RP-HPLC method for the determination of Valacyclovir hydrochloride and its related substances in tablet formulation", 《NT. J. PHARM. SCI. REV. RES.》 * |
| 周一萌 等: "盐酸伐昔洛韦含量及其有关物质的HPLC法测定", 《中国医药工业杂志》 * |
| 徐玉红 等: "RP-HPLC测定盐酸伐昔洛韦分散片的含量及有关物质", 《实用药物与临床》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115745997A (en) * | 2022-11-30 | 2023-03-07 | 湖北省宏源药业科技股份有限公司 | Preparation method of high-purity valaciclovir impurity H |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110940754B (en) | High performance liquid chromatography method for separating and measuring impurities in valacyclovir hydrochloride | |
| CN102798678B (en) | Detection method and content determining method of sodium calcium edetate in pantoprazole sodium for injecting | |
| CN112903838A (en) | Method for determining related substances in Favilavir | |
| CN109060973B (en) | Method for detecting ethylenediamine in lipoic acid injection | |
| WO2023124924A1 (en) | Method for detecting residual solvent in pingyangmycin hydrochloride bulk drug | |
| US20240044851A1 (en) | Method for detecting content of active ingredients of compound sophorae flavescentis radix injection and fingerprint spectrum thereof | |
| CN111879868A (en) | Method for determining related substances of valacyclovir hydrochloride | |
| CN111579704A (en) | Method for detecting content of N, N' -diacetyl-L-cystine in compound amino acid injection | |
| CN113484430B (en) | Method for measuring related substances of L-alanine isopropyl ester hydrochloride by adopting high performance liquid chromatography | |
| CN101658550A (en) | Method for measuring content of selfheal oral liquid | |
| CN111551645A (en) | Method for detecting hydroxychloroquine sulfate related substances and application thereof | |
| CN113030285A (en) | Method for detecting residual 2-bromomethyl-1, 3-dioxolane in doxofylline | |
| CN103185750A (en) | Mass control method for clopidogrel splitting agent | |
| CN115266998A (en) | Method for detecting content of sodium ions in sodium salt molecules | |
| CN110824059B (en) | Detection method of formyl impurities in febuxostat | |
| CN111380982B (en) | Method for detecting content of 2-chloroethanol in cloperamide hydrochloride raw material | |
| CN113063881A (en) | Related substance analysis method of entecavir oral solution | |
| CN110187021B (en) | Method for simultaneously determining contents of two main drugs in closantel sodium ivermectin injection | |
| CN114113402B (en) | Method for measuring pinanediol content in bortezomib by adopting high performance liquid chromatography | |
| CN110045045B (en) | Method for detecting content of hyaluronic acid in facial mask | |
| CN114152702B (en) | Method for determining content of potassium dehydroandrograpolide succinate for injection | |
| CN112730637B (en) | HPLC detection method for related substances of L-malic acid | |
| CN112394110A (en) | Method for detecting content of hydroxychloroquine sulfate ester impurities in hydroxychloroquine sulfate | |
| CN117890496A (en) | Method for detecting related substances of compound preparation of novel oral solution of guaifenesin | |
| CN112394112A (en) | Method for detecting content of hydroxychloroquine nitrogen oxide impurities in hydroxychloroquine sulfate |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201103 |