CN111175385B - Irbesartan isomer testing method in irbesartan - Google Patents
Irbesartan isomer testing method in irbesartan Download PDFInfo
- Publication number
- CN111175385B CN111175385B CN201811337972.4A CN201811337972A CN111175385B CN 111175385 B CN111175385 B CN 111175385B CN 201811337972 A CN201811337972 A CN 201811337972A CN 111175385 B CN111175385 B CN 111175385B
- Authority
- CN
- China
- Prior art keywords
- solution
- irbesartan
- isomer
- test
- blank
- 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
Abstract
The invention relates to the field of organic chemistry and pharmaceutical analysis, in particular to a test method for separating and determining irbesartan isomers in irbesartan by high performance liquid chromatography, which mainly comprises the following steps: (1) Determining chromatographic conditions through chromatographic columns, column temperature, detection wavelength and flow equality; (2) Preparing blank solution, reference substance, test sample and other solutions; (3) The measuring method comprises precisely measuring blank solution, reference solution and sample solution, respectively, injecting into a liquid chromatograph, and recording chromatogram; and (4) calculating. The detection method has high chromatographic peak separation degree and high system applicability, and meets the standards in the aspects of specificity, precision, quantitative limit, detection limit, accuracy, linearity, range, durability and the like.
Description
Technical Field
The invention relates to the field of organic chemistry and pharmaceutical analysis, in particular to a method for testing an irbesartan isomer.
Background
Irbesartan (irbesart) has the chemical name: 3- ((2 '- (1H-tetrazol-5-yl) - [1,1' -biphenyl ] -4-yl) methyl) -2-butyl-1, 3-diazaspiro [4,4] non-1-en-4-one, developed by Sanofi and marketed in the United kingdom at the earliest in 1997. Irbesartan is an angiotensin II receptor (AT 1 subtype) antagonist that blocks angiotensin II induced vasoconstriction and aldosterone secretion by selectively binding to the AT1 angiotensin II receptor. The medicine can be used for treating adult essential hypertension, and can be used as part of antihypertensive drug treatment scheme for treating nephropathy of adult patients with hypertension and type 2 diabetes.
At present, in the aspect of quality control of irbesartan raw material drugs, the irbesartan, an impurity I and other impurities in raw material drugs are mainly detected, and a potential process impurity, namely an irbesartan isomer exists in the irbesartan preparation process, and the irbesartan isomer has the chemical name: 1- ((2 '- (1H-tetrazol-5-yl) - [1,1' -biphenyl ] -4-yl) methyl) -2-butyl-1, 3-diazaspiro [4,4] non-1-en-4-one.
At present, reports about irbesartan isomers are few, only the preparation methods of irbesartan isomers and irbesartan condensation compound isomers as intermediates thereof are disclosed in patent document CN106083826A, and no detection method about irbesartan isomers is found.
Disclosure of Invention
The invention aims to provide a rapid and accurate method for testing irbesartan isomerides, which is implemented by high performance liquid chromatography and verified in the aspects of system adaptability, specificity, precision, quantitative limit, detection limit, durability and the like by referring to related contents of Chinese pharmacopoeia.
The method for testing the irbesartan isomeride mainly comprises the following steps:
(1) Chromatographic conditions
The instrument comprises: a chromatographic column: octadecylsilane chemically bonded silica is used as a filling agent; the flow rate is 1.0 plus or minus 0.2ml/min; detection wavelength: 220 +/-5 nm; sample introduction amount: 10 +/-2 mul; column temperature: 25 +/-2 ℃; operating time: 20 plus or minus 3min; mobile phase: mixing the following raw materials in a phosphoric acid solution: the volume of acetonitrile is 65:35;
the preparation method of the phosphoric acid solution comprises the steps of taking 5.5ml of 85 percent phosphoric acid, adding 950ml of water, and adjusting the pH value to 3.2 by triethylamine;
(2) Preparing a solution: the diluent is methanol; the blank solution is a diluent; irbesartan isomer stock solution: the irbesartan isomer control substance has the concentration of 5 mug/ml; control solution: irbesartan isomer control substance concentration is 0.5 mu g/ml; test solution: the irbesartan test sample concentration is 0.5mg/ml;
(3) Measuring method and calculation formula
Injecting the blank solution, the reference solution and the sample solution into a liquid chromatograph, recording the chromatogram, and obtaining the result% = (R) U /Rs)×(Cs/C U ) X 100, wherein: r U Peak areas of irbesartan isomers in a test sample solution spectrum; rs-5 reference mean peak area of irbesartan isomer in reference solution chromatogram; cs-Er in control solutionThe concentration of the besartan isomer is mg/ml; c U The concentration of the test solution is mg/ml.
Further, the irbesartan isomer limits are as follows:
| name (R) | Acceptability criteria% | LOQ％ | LOD％ |
| Irbesartan isomer (RRT ≈ 0.4) | ≤0.1 | 0.03 | 0.01 |
Further, the method for testing irbesartan isomer in irbesartan also comprises a method verification before detection, and the chromatographic conditions verified by the method are consistent with those in the test method, and the specific contents are as follows:
(1) System adaptability
Chromatographic conditions are as follows: as described above.
Solution preparation: diluent, blank solution and control solution were as described above
The measuring method comprises the following steps: and respectively injecting the blank solution and the reference solution into a liquid chromatograph, and recording the chromatogram.
(2) Specificity
Chromatographic conditions are as follows: as described above.
Solution preparation: besides the diluent, the blank solution, the stock solution, the reference solution and the test solution, the reagent kit also comprises a selective solution, and the preparation method comprises the following steps: taking an irbesartan sample of about 25mg, precisely weighing, placing in a 50ml volumetric flask, adding a proper amount of diluent for dissolution, precisely transferring 5.0ml of irbesartan isomer stock solution into the flask, adding the diluent for dilution to a scale, and shaking up uniformly. ( Concentration: irbesartan 0.5mg/ml; irbesartan isomer 0.5. Mu.g/ml )
The determination method comprises the following steps: and respectively injecting the blank solution, the reference solution, the test solution and the selective solution into a liquid chromatograph, and recording the chromatogram.
(3) Selectivity is
Chromatographic conditions are as follows: as described above.
Solution preparation: the diluent, blank solution, stock solution, control solution, test solution and optional solution are as described above.
The determination method comprises the following steps: and respectively injecting the reference solution, the test solution and the selective solution into a liquid chromatograph, and recording the chromatogram.
(4) Repeatability
Chromatographic conditions are as follows: as described above.
Solution preparation: the diluent, blank solution, stock solution, control solution and test solution are as described above.
The measuring method comprises the following steps: and respectively injecting the reference substance solution and the test solution into a liquid chromatograph, and recording the chromatogram.
(5) Limit of quantitation and limit of detection
Chromatographic conditions are as follows: as described above.
Solution preparation: the diluent, blank solution and stock solution are as above, and also include the following solutions,
test solution a: precisely transferring 6.0ml of irbesartan isomer stock solution, putting the irbesartan isomer stock solution into a 20ml volumetric flask, adding a diluent to dilute the irbesartan isomer stock solution to a scale, and shaking the solution uniformly.
LOQ solution: adjusting the dilution ratio according to the S/N value of the spectrum obtained by the test solution a until the S/N of the irbesartan isomer is approximately equal to 10; 6 parts of the solution is prepared by the same method.
LOD solution: precisely transferring 3.0ml of LOQ solution into a 10ml volumetric flask, adding diluent to dilute to the scale, and shaking up.
The determination method comprises the following steps: and respectively injecting the test sample solution a, the LOQ solution and the LOD solution into a liquid chromatograph, and recording the chromatogram.
(6) Stability of solution
Chromatographic conditions are as follows: as described above.
Solution preparation: the diluent, blank solution, control solution and test solution are as described above.
The measuring method comprises the following steps: taking 3 parts of the reference solution and the sample solution, respectively standing at room temperature for 0 day, 1 day and 2 days, respectively injecting into a liquid chromatograph, and recording chromatogram.
Further, the data acceptance criteria obtained in the method verification are as follows:
advantageous effects
According to the technical scheme, the detection method makes up the blank of the irbesartan isomer detection method in irbesartan, provides a quick and accurate irbesartan isomer detection method, and facilitates quality control of irbesartan raw material medicines. In addition, the detection method has high chromatographic peak separation degree and high system applicability, and simultaneously meets the standards on specificity, precision, quantitative limit, detection limit, accuracy, linearity, range and durability.
Drawings
FIG. 1: a blank solution spectrogram;
FIG. 2: a system suitability solution profile;
FIG. 3: a spectrogram of the control solution;
FIG. 4: a spectrogram of the test solution;
FIG. 5: a selective solution spectrum;
FIG. 6: detecting a spectrogram through precision;
FIG. 7 is a schematic view of: detecting a spectrogram through quantitative limit;
FIG. 8: verifying a spectrogram of the detection limit;
FIG. 9: solution stability verification-the control solution is placed for 0 day spectrogram;
FIG. 10: solution stability verification-the control solution was left for 2 days spectrogram;
FIG. 11: verifying the stability of the solution, namely placing the test solution in a 0-day spectrogram;
FIG. 12: verifying the stability of the solution, namely placing the test solution for 2 days;
Detailed Description
The following examples illustrate the invention in detail to aid understanding, but are not intended to limit the invention.
Example 1
Examination of irbesartan isomers in irbesartan:
(1) Chromatographic conditions
The instrument comprises the following steps: the high performance liquid chromatograph is provided with an ultraviolet detector, an electronic analytical balance and a pH meter
A chromatographic column: octadecylsilane chemically bonded silica is used as a filling agent; (e.g., thermo Acclaim 120C 18,5 μm, 4.6X 150mm or equivalent performance column);
flow rate: 1.0ml/min; detection wavelength: 220nm;
sample introduction amount: 10 mul; column temperature: 25 ℃;
operating time: 20min;
mobile phase: adding a phosphoric acid solution (5.5 ml of 85% phosphoric acid, 950ml of water and adjusting the pH value to 3.2 by triethylamine): acetonitrile =65:35 (V/V).
(2) Solution preparation:
diluting liquid: methanol;
blank solution: diluting the solution;
irbesartan isomer stock solution: taking an irbesartan isomer reference substance of about 10mg, precisely weighing, placing in a 100ml volumetric flask, adding a diluent to dissolve and dilute to a scale, and shaking up. Accurately transferring 5.0ml, placing in a 100ml volumetric flask, adding the diluent to dilute to the scale, and shaking up. (concentration: 5. Mu.g/ml)
Control solution, i.e. control solution: precisely transferring 5.0ml of irbesartan isomer stock solution, putting the irbesartan isomer stock solution into a 50ml volumetric flask, adding diluent to dilute the irbesartan isomer stock solution to a scale, and shaking the irbesartan isomer stock solution uniformly. (concentration: 0.5. Mu.g/ml)
Test solution, i.e. test solution: taking an irbesartan sample of about 25mg, precisely weighing, placing in a 50ml volumetric flask, adding a diluent to dissolve and dilute to a scale, and shaking uniformly. (concentration: 0.5 mg/ml)
(3) Measurement method
After the system is stabilized, respectively injecting blank solution 1 needle, reference solution 5 needle and sample solution 1 needle into liquid chromatograph, recording chromatogram
(4) Formula for calculation
Result% = (R) U /Rs)×(Cs/C U )×100
Wherein: r U : peak areas of irbesartan isomers in a test solution spectrum;
rs:5 mean peak areas of irbesartan isomers in a control solution map;
cs: concentration of irbesartan isomer (mg/ml) in a control solution;
C U : concentration of test solution (mg/ml).
(5) Limit of
Calculated from experimentally determined data, the irbesartan isomer limits are shown in the following table:
TABLE-1 Irbesartan isomeric limits
| Name (R) | Acceptable Standard% | LOQ％ | LOD％ |
| Irbesartan isomer (RRT ≈ 0.4) | ≤0.1 | 0.03 | 0.01 |
Example 2 system adaptability:
chromatographic conditions are as follows: as described in example 1.
Solution preparation: diluent, blank solution and control solution were as described in example 1
The determination method comprises the following steps: and after the system is stabilized, injecting 1 needle of the blank solution and 5 needles of the reference substance solution into the liquid chromatograph respectively, and recording the chromatogram.
And (3) measuring results: according to the measured spectrogram, the measurement results of the system applicability solution are shown in the following table:
TABLE-2 System applicability solution determination results
Example 3 specificity:
chromatographic conditions are as follows: as described in example 1.
Solution preparation: besides the diluent, blank solution, reference solution and test solution in the above example 1, the preparation method further comprises a selective solution, and the preparation method comprises the following steps: taking an irbesartan sample of about 25mg, precisely weighing, placing in a 50ml volumetric flask, adding a proper amount of diluent for dissolution, precisely transferring 5.0ml of irbesartan isomer stock solution into the flask, adding the diluent for dilution to a scale, and shaking up. ( Concentration: irbesartan 0.5mg/ml; irbesartan isomer 0.5. Mu.g/ml )
The determination method comprises the following steps: and after the system is stable, injecting a blank solution 1 needle, a reference solution 3 needle, a sample solution 1 needle and a selective solution 3 needle into the liquid chromatograph respectively, and recording the chromatogram.
And (3) measuring results: the results of the specificity test are shown in the following table:
TABLE-3 results of specificity test
Example 4 selectivity:
chromatographic conditions are as follows: as described in example 1.
Solution preparation: the control solution, test solution, and selection solution were as described in example 3.
The determination method comprises the following steps: and after the system is stable, respectively injecting 3 needles of the reference solution, 1 needle of the test solution and 3 needles of the selective solution into a liquid chromatograph, and recording the chromatogram.
And (3) measuring results: results of the specificity selectivity measurements are shown in the following table:
TABLE-4 results of specificity selectivity determination
Remarking: carry-in peak area = test sample solution peak area x test sample amount ÷ test sample amount in test sample solution
Example 5 repeatability:
chromatographic conditions are as follows: as described in example 1.
Solution preparation: the diluent, blank solution, stock solution, control solution and test solution were as described in example 1.
The measuring method comprises the following steps: and after the system is stabilized, respectively injecting 1 needle of the reference solution and 1 needle of each of 6 parts of the test solution into a liquid chromatograph, and recording the chromatogram.
And (3) measuring results: the results of the reproducibility measurements are shown in the following table,
TABLE-5 measurement of precision
Note: the control solution referencing system is applicable to a first needle.
Example 6 limits of quantitation and detection
Chromatographic conditions are as follows: as described in example 1.
Solution preparation: dilutions, blank solutions, isomer stocks as described in example 1, also included the following solutions,
test solution a: precisely transferring 6.0ml of irbesartan isomer stock solution, putting the irbesartan isomer stock solution into a 20ml volumetric flask, adding a diluent to dilute the irbesartan isomer stock solution to a scale, and shaking the solution uniformly.
LOQ solution: adjusting the dilution ratio according to the S/N value of the spectrum obtained by the test solution a until the S/N of the irbesartan isomer is approximately equal to 10; 6 parts of the solution is prepared by the same method.
LOD solution: precisely transferring 3.0ml of LOQ solution into a 10ml volumetric flask, adding diluent to dilute to the scale, and shaking up.
The determination method comprises the following steps: and after the system is stabilized, injecting the sample solution a 1, 6 parts of LOQ solution and LOD solution into a liquid chromatograph, and recording the chromatogram. And (3) measuring results:
TABLE-6 results of measurement of quantitative limit and detection limit
TABLE-7 LOQ repeatability results
EXAMPLE 7 solution stability
Chromatographic conditions are as follows: as described in example 1.
Solution preparation: the diluent, blank solution, control solution, and test solution were as described in example 1.
The determination method comprises the following steps: after the reference solution and the sample solution are placed at room temperature for 0 day, 1 day and 2 days, respectively injecting 1 needle of the reference solution for 0 day, 1 day and 2 days and 1 needle of the sample solution for 0 day, 1 day and 2 days into a liquid chromatograph when the system is stable, and recording the chromatogram.
And (3) measuring results:
TABLE-8 results of solution stability measurements
Claims (3)
1. A method for testing irbesartan isomer 1- ((2 '- (1H-tetrazol-5-yl) - [1,1' -biphenyl ] -4-yl) methyl) -2-butyl-1, 3-diazaspiro [4,4] non-1-en-4-one in irbesartan, the structure of which is shown as the following figure, is characterized by comprising the following steps of:
(1) Chromatographic conditions
The apparatus comprises: and (3) chromatographic column: octadecylsilane chemically bonded silica is used as a filling agent; the flow rate is 1.0 plus or minus 0.2ml/min; detection wavelength: 220 +/-5 nm; sample injection amount: 10 +/-2 mul; column temperature: 25 +/-2 ℃; operating time: 20 +/-3 min; mobile phase: mixing the following components in a phosphoric acid solution: the volume of acetonitrile is 65:35; the preparation method of the phosphoric acid solution comprises the steps of taking 5.5ml of 85% phosphoric acid, adding 950ml of water, and adjusting the pH value to 3.2 by using triethylamine;
(2) Preparing a solution: the diluent is methanol; the blank solution is a diluent; irbesartan isomer stock solution: the irbesartan isomer control substance has the concentration of 5 mug/ml; control solution: the irbesartan isomer control substance concentration is 0.5 mug/ml; test solution: the irbesartan test sample concentration is 0.5mg/ml;
(3) The measurement method and the calculation formula respectively inject a blank solution, a reference solution and a sample solution into a liquid chromatograph, record a chromatogram, and obtain the result of% = (RU/Rs) × (Cs/CU) × 100, wherein: RU-peak area of irbesartan isomer in a test sample solution map; the average peak area of irbesartan isomer in an Rs-5 reference substance solution spectrum; cs-concentration mg/ml of irbesartan isomer in control solution; CU refers to the concentration mg/ml of the test solution.
2. The assay of claim 1, wherein the irbesartan isomer limit is:
。
3. The test method according to claim 1, further comprising a method validation prior to the detection, wherein the chromatographic conditions validated by the method are consistent with the chromatographic conditions of the test method as follows:
(1) System adaptability
Chromatographic conditions are as follows: as claimed in claim 1;
solution preparation: the diluent, blank solution and control solution are as described in claim 1;
the measuring method comprises the following steps: respectively injecting the blank solution and the reference solution into a liquid chromatograph, and recording a chromatogram;
(2) Specificity property
Chromatographic conditions are as follows: as claimed in claim 1;
solution preparation: besides the diluent, the blank solution, the stock solution, the reference solution and the test solution, the selective solution also comprises a selective solution, wherein the irbesartan concentration is 0.5mg/ml, and the irbesartan isomer concentration is 0.5 mu g/ml;
the measuring method comprises the following steps: respectively injecting the blank solution, the reference solution, the test solution and the selective solution into a liquid chromatograph, and recording a chromatogram;
(3) Selectivity is
Chromatographic conditions are as follows: as claimed in claim 1;
solution preparation: diluting solution, blank solution, stock solution, reference solution, sample solution and optional solution as described in (2) specificity step;
the determination method comprises the following steps: injecting the reference solution, the test solution and the selective solution into a liquid chromatograph, and recording the chromatogram;
(4) Repeatability of
Chromatographic conditions are as follows: as claimed in claim 1;
solution preparation: diluting solution, blank solution, stock solution, reference solution, and sample solution as described in (2) specificity step;
the determination method comprises the following steps: respectively injecting the reference substance solution and the test solution into a liquid chromatograph, and recording chromatograms;
(5) Limit of quantitation and limit of detection
Chromatographic conditions are as follows: as claimed in claim 1;
solution preparation: the diluent, blank solution and stock solution as described in (2) the specific steps further include the following solutions:
test solution a: precisely transferring 6.0ml of irbesartan isomer stock solution, placing the irbesartan isomer stock solution into a 20ml volumetric flask, adding a diluent to dilute the irbesartan isomer stock solution to a scale, and shaking the solution uniformly;
LOQ solution: adjusting the dilution ratio according to the S/N value of the spectrum obtained by the test solution a until the S/N of the irbesartan isomer is approximately equal to 10; preparing 6 parts of the solution by the same method;
LOD solution: precisely transferring 3.0ml of LOQ solution into a 10ml volumetric flask, adding diluent to dilute to a scale, and shaking up;
the measuring method comprises the following steps: respectively injecting the test sample solution a, the LOQ solution and the LOD solution into a liquid chromatograph, and recording a chromatogram;
(6) Stability of solution
Chromatographic conditions are as follows: as claimed in claim 1;
solution preparation: diluting solution, blank solution, reference solution, and sample solution as described in (2);
the determination method comprises the following steps: taking 3 parts of the reference solution and the sample solution, respectively standing at room temperature for 0 day, 1 day and 2 days, respectively injecting into a liquid chromatograph, and recording chromatogram.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811337972.4A CN111175385B (en) | 2018-11-12 | 2018-11-12 | Irbesartan isomer testing method in irbesartan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811337972.4A CN111175385B (en) | 2018-11-12 | 2018-11-12 | Irbesartan isomer testing method in irbesartan |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111175385A CN111175385A (en) | 2020-05-19 |
| CN111175385B true CN111175385B (en) | 2023-02-07 |
Family
ID=70648099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811337972.4A Active CN111175385B (en) | 2018-11-12 | 2018-11-12 | Irbesartan isomer testing method in irbesartan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111175385B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114577971A (en) * | 2020-11-30 | 2022-06-03 | 珠海润都制药股份有限公司 | Method for detecting biphenyl imidazoline isomer in irbesartan |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2886642B1 (en) * | 2005-06-06 | 2008-05-30 | Sanofi Aventis Sa | IRBESARTAN ALKALINE-EARTH SALTS AND THEIR PREPARATION |
| EA014585B1 (en) * | 2005-09-14 | 2010-12-30 | Арес Трейдинг С.А. | Method for the determination of poloxamers |
| CN106083826A (en) * | 2016-06-22 | 2016-11-09 | 浙江华海药业股份有限公司 | A kind of irbesartan isomer and the preparation method of intermediate thereof |
| CN106706785B (en) * | 2016-12-23 | 2019-02-26 | 东药集团沈阳施德药业有限公司 | A method of using substance related in high performance liquid chromatography detection irbesartan and hydrochlorthiazide piece |
| CN107028912B (en) * | 2017-05-31 | 2019-03-19 | 珠海润都制药股份有限公司 | A kind of preparation method of Irbesartan Capsules |
| CN108191836A (en) * | 2018-01-17 | 2018-06-22 | 珠海润都制药股份有限公司 | A kind of preparation method of low electrostatic Irbesartan bulk pharmaceutical chemicals |
-
2018
- 2018-11-12 CN CN201811337972.4A patent/CN111175385B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN111175385A (en) | 2020-05-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111693633B (en) | Method for detecting 3,4-dimethoxy benzoyl chloride in itopride hydrochloride | |
| CN111103372A (en) | Method for detecting related substances of procaterol hydrochloride intermediate | |
| CN115453012B (en) | Reversed-phase HPLC method for simultaneously measuring multiple positional isomers in voathixetine hydrobromide | |
| CN111089907B (en) | Method for testing irbesartan cyano impurity isomer | |
| CN111175385B (en) | Irbesartan isomer testing method in irbesartan | |
| CN107870209B (en) | Method for determining impurity content in linagliptin bulk drug | |
| CN108061767B (en) | Method for separating and measuring rivaroxaban intermediate and related impurities thereof by HP L C method | |
| CN111077232B (en) | Inspection method of Sacubitril valsartan sodium related substances | |
| CN111679029B (en) | Method for detecting p-hydroxybenzaldehyde in itopride hydrochloride | |
| Ghosh et al. | Development of stability indicating RP-HPLC method and validation for the estimation of vilazodone hydrochloride | |
| CN113484430A (en) | Method for determining L-alanine isopropyl ester hydrochloride related substances by adopting high performance liquid chromatography | |
| CN106546689A (en) | A kind of HPLC analysis methods of amber love song Ge Lieting bulk drugs and its preparation enantiomter | |
| CN114544842B (en) | Method for detecting N-bromosuccinimide in voriconazole | |
| CN114646701A (en) | HPLC (high Performance liquid chromatography) test method for related substances in L-prolinamide | |
| CN115774061A (en) | Method for detecting acetic acid in 1-cyclohexyl piperazine | |
| CN114594168A (en) | Method for detecting indobufen impurity | |
| CN109239214B (en) | Method for detecting Shakubiqu isomers in Shakubiqu sodium | |
| CN114624339A (en) | Analysis method for determining indobufen impurities | |
| CN114354780B (en) | Method for detecting impurity content in ammonia bromine terro oral solution | |
| CN113219105B (en) | Detection method of 2-nitro-4-methoxyaniline in esomeprazole magnesium and intermediate thereof | |
| CN112014479A (en) | Method for detecting n-valeryl chloride in valsartan | |
| CN117310021B (en) | Method for separating and detecting related substances of ubenimex by high performance liquid chromatography | |
| CN113466360B (en) | Azilsartan 6 related substance detection method | |
| CN115494183B (en) | Method for detecting 1,2, 4-triazole in triazole medicines | |
| CN114235972B (en) | Method for determining content of linagliptin impurity RBP-1 |
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 |