CN119224184B - A gas chromatography detection method for 2,5-dimethoxytetrahydrofuran related substances - Google Patents
A gas chromatography detection method for 2,5-dimethoxytetrahydrofuran related substances Download PDFInfo
- Publication number
- CN119224184B CN119224184B CN202411754707.1A CN202411754707A CN119224184B CN 119224184 B CN119224184 B CN 119224184B CN 202411754707 A CN202411754707 A CN 202411754707A CN 119224184 B CN119224184 B CN 119224184B
- Authority
- CN
- China
- Prior art keywords
- impurity
- dimethoxytetrahydrofuran
- solution
- related substances
- gas chromatography
- 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
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
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/64—Electrical detectors
- G01N30/68—Flame ionisation detectors
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 Analysing Biological Materials (AREA)
Abstract
The invention solves the problems existing in the prior art, provides a gas chromatography detection method of 2, 5-dimethoxy tetrahydrofuran related substances, has simple and convenient operation, good specificity, linearity and precision, high sensitivity and good method durability, can be used for quality control of compound (Va), namely 2, 5-dimethoxy tetrahydrofuran, and meets the process requirements.
Description
Technical Field
The invention belongs to the technical field of medicine analysis, and particularly relates to a gas chromatography method for separating and detecting 2, 5-dimethoxy tetrahydrofuran related substances.
Background
Ilaprazole is known as 2- [ (RS) - [ (4-methoxy-3-methylpyridin-2-yl) methyl ] sulfinyl ] -5- (1H-pyrrol-1-yl) -1H-benzimidazole (CAS: 172152-36-2), is a powerful proton pump inhibitor, acts by interfering with the proton pump secreting gastric acid on cells of the stomach wall, has the strongest gastric acid inhibition effect in similar drugs, and is mainly used for duodenal ulcers, gastric ulcers, reflux esophagitis and the like in adults.
The compound (Va), namely 2, 5-dimethoxy tetrahydrofuran (CAS number: 696-59-3), is a key starting material for preparing ilaprazole bulk drug, and has the following structural formula:
Compound (Va) is usually obtained by catalytic hydrogenation of 2, 5-dimethoxydihydrofuran (CAS number 332-77-4), and consists of a mixture of cis and trans isomers. According to the chemical structure and the preparation process of the compound (Va), process impurities and degradation impurities possibly exist, and the compound directly participates in the reaction in the synthesis process to generate process byproduct impurities corresponding to ilaprazole. Is difficult to remove during the synthesis process, thereby possibly affecting the quality of the final product ilaprazole. Since the compound (Va) and its related impurities are low boiling point substances which are not absorbed by ultraviolet rays, it is necessary to establish a method for detecting the compound (Va) in the gas phase.
The existing method is to search the enterprise standard (standard number: Q/420682GL 02-2023) of the Laohou optical-coupling technology Co., ltd.) for 2, 5-dimethoxy tetrahydrofuran quality standard, wherein the content determination method of 2, 5-dimethoxy tetrahydrofuran is gas chromatography, and the main component content is determined by using an area normalization method. The method has short retention time of main peaks and impurity peaks, can only roughly examine the content of the main component of the 2, 5-dimethoxy tetrahydrofuran, combines other impurities after the main peaks to form peaks, has poor separation degree from the main peaks, and cannot realize the quality control of ilaprazole.
Disclosure of Invention
The invention solves the problems existing in the prior art, provides a gas chromatography detection method of 2, 5-dimethoxy tetrahydrofuran related substances, has simple and convenient operation, good specificity, linearity and precision, high sensitivity and good method durability, can be used for quality control of ilaprazole initial material compound (Va), namely 2, 5-dimethoxy tetrahydrofuran, and meets the process requirements.
The invention provides a gas chromatography detection method of 2, 5-dimethoxy tetrahydrofuran related substances, which comprises the following steps of respectively taking a separation degree solution and a sample solution for sample injection, detecting according to gas chromatography conditions, recording a chromatogram, and calculating the detection amount of single impurities and total impurities according to a peak area normalization method;
the structures of the related substances are as follows:
;
Wherein the impurity Va-1 is a starting material of the compound (Va), the impurities Va-2, va-3 and Va-4 are process impurities of the compound (Va), and succinyl aldehyde and methanol are degradation impurities of the compound (Va).
The chromatographic conditions are as follows:
instrument, agilent gas chromatograph, hydrogen Flame Ionization Detector (FID);
A chromatographic column is a capillary column taking 6% cyanopropylphenyl-94% dimethylpolysiloxane as a fixing solution;
The column temperature is that the initial temperature is 35-70 ℃, the temperature is maintained for 0-5 minutes, the temperature is raised to 200-240 ℃ at the rate of 10-20 ℃ per minute, the temperature is maintained for 10-20 minutes, the temperature is preferably 55-65 ℃ for 2 minutes, the temperature is raised to 240 ℃ at the rate of 12-18 ℃ per minute, and the temperature is maintained for 12 minutes;
the temperature of the sample inlet is 150-250 ℃, preferably 200 ℃;
Carrier gas, nitrogen;
the flow rate of carrier gas is 0.9-1.1 ml/min;
The temperature of the detector is 200-300 ℃, preferably 250 ℃;
The split ratio is 50:1-150:1, preferably 100:1;
The sample amount was 1. Mu.l.
Wherein the chromatographic column is DB-624, the inner diameter is 0.32mm, the length is 60m, and the film thickness is 1.8 mu m.
The preparation method of the test solution comprises dissolving compound (Va) in solvent, and diluting to obtain solution containing 0.1g per 1 ml.
The preparation method of the separation degree solution comprises taking appropriate amounts of methanol, impurity Va-2 reference substance, succinaldehyde reference substance, impurity Va-3 reference substance, impurity Va-1 reference substance and impurity Va-4 reference substance, placing into the same measuring flask, diluting with solvent to scale, shaking, and collecting as impurity stock solution. Putting a proper amount of the compound (Va) into a measuring flask, adding a proper amount of an impurity stock solution, diluting to a scale with a solvent, and shaking uniformly to obtain the compound (Va).
The solvent is selected from one or more of acetonitrile, ethanol, acetone and dichloromethane, preferably acetonitrile.
The invention provides a gas chromatography detection method of 2, 5-dimethoxy tetrahydrofuran related substances, which comprises the following steps of respectively taking a separation degree solution and a sample solution for sample injection, detecting according to gas chromatography conditions, recording a chromatogram, and calculating the detection amount of single impurities and total impurities according to a peak area normalization method;
the structures of the related substances are as follows:
;
the chromatographic conditions are as follows:
instrument, agilent gas chromatograph, hydrogen Flame Ionization Detector (FID);
A chromatographic column is a capillary column taking 6% cyanopropylphenyl-94% dimethylpolysiloxane as a fixing solution;
Column temperature, which is to raise the temperature to 240 ℃ at a rate of 15 ℃ per minute for 12 minutes, at an initial temperature of 60 ℃ for 2 minutes;
The temperature of the sample inlet is 200 ℃;
Carrier gas, nitrogen;
Carrier gas flow rate 1.0ml/min;
detector temperature 250 ℃;
the split ratio is 100:1;
The sample amount was 1. Mu.l.
Wherein the chromatographic column is DB-624, the inner diameter is 0.32mm, the length is 60m, and the film thickness is 1.8 mu m.
The preparation method of the test solution comprises placing 1.0g of compound (Va) in a 10ml measuring flask, adding acetonitrile, dissolving to scale, and shaking.
The preparation method of the separation degree solution comprises taking methanol, impurity Va-2 reference substance, succinaldehyde reference substance, impurity Va-3 reference substance, impurity Va-1 reference substance and impurity Va-4 reference substance respectively 25mg, placing into the same 5ml measuring flask, diluting with acetonitrile to scale, shaking, and collecting as impurity stock solution. Taking 0.2g of compound (Va), placing the compound (Va) into a 2ml measuring flask, adding 0.2ml of impurity stock solution, diluting to a scale with acetonitrile, and shaking uniformly to obtain the compound.
The invention further provides an application of the gas chromatography detection method of the 2, 5-dimethoxy tetrahydrofuran related substance in ilaprazole quality control.
The beneficial technical effects of the invention are as follows:
(1) The invention provides a detection method of a related substance of ilaprazole starting material compound (Va), namely 2, 5-dimethoxy tetrahydrofuran, which can realize effective separation of two components and impurities of the compound (Va), namely 2, 5-dimethoxy tetrahydrofuran (cis-trans isomer mixture).
(2) The detection method disclosed by the invention is simple and convenient to operate, good in specificity, linearity and precision, high in sensitivity and good in method durability, can be used for quality control of ilaprazole starting material compound (Va), namely 2, 5-dimethoxy tetrahydrofuran, and meets the process requirements.
Drawings
FIG. 1 is a chromatogram of example 1 under conditions ①.
FIG. 2 is a chromatogram of example 1 under conditions ②.
FIG. 3 is a chromatogram of example 1 under conditions ③.
FIG. 4 is a chromatogram of the resolution solution of example 2.
FIG. 5 is a chromatogram of the resolution solution of example 2.
FIG. 6 is a graph of the linear test of example 3.
FIG. 7 is a quantitative limit chromatogram of compound (Va) of example 4.
FIG. 8 is a quantitative limit chromatogram of impurity Va-3 of example 4.
FIG. 9 is a quantitative limit chromatogram of other impurities in example 4.
FIG. 10 is a detection limit chromatogram of Compound (Va) of example 4.
FIG. 11 is a diagram showing the detection limit of the impurity Va-3 in example 4.
Fig. 12 is a diagram showing the detection limits of other impurities in example 4.
FIG. 13 is a chart of the precision test of example 5.
FIG. 14 is a stability test chart of example 6.
FIG. 15 is a chromatogram of example 7 with different chromatographic conditions and durability.
Fig. 16 is a chromatogram of example 7 for different carrier gas flow rates for chromatographic conditions durability.
FIG. 17 is a graph of column temperature chromatograms of example 7 with different chromatographic condition durability.
Detailed Description
The following detailed description of specific embodiments of the invention is provided for purposes of illustration only and is not to be construed as limiting the invention.
Preparing a solution:
The preparation of test solution comprises dissolving compound (Va) in acetonitrile, and diluting to obtain solution containing 0.1g per 1 ml.
Preparing a separation degree solution, namely taking 25mg of methanol, an impurity Va-2 reference substance, a succinyl aldehyde reference substance, an impurity Va-3 reference substance, an impurity Va-1 reference substance and an impurity Va-4 reference substance respectively, placing the methanol, the impurity Va-2 reference substance, the succinyl aldehyde reference substance, the impurity Va-3 reference substance and the impurity Va-4 reference substance into the same 5ml measuring flask, diluting with acetonitrile to scale, and shaking uniformly to serve as an impurity stock solution. Taking 0.2g of compound (Va), placing the compound (Va) into a 2ml measuring flask, adding 0.2ml of impurity stock solution, diluting to a scale with acetonitrile, and shaking uniformly to obtain the compound.
Example 1 chromatographic condition selection
① Reference is made to chromatographic conditions in the Laohou optical coupling technology Co., ltd (standard number: Q/420682GL 02-2023): 2, 5-dimethoxy tetrahydrofuran quality standard:
instrument, agilent gas chromatograph, hydrogen Flame Ionization Detector (FID);
Chromatographic column A capillary column with 5% phenyl-95% dimethylpolysiloxane as stationary liquid is used as chromatographic column (HP-5, 0.32 mm. Times.60 m,1.0 μm);
Column temperature, namely, 150 ℃ and 30min;
Carrier gas, nitrogen;
Carrier gas flow rate 1.0ml/min;
The temperature of the sample inlet is 200 ℃;
detector temperature 250 ℃;
the split ratio is 100:1;
The sample amount was 1. Mu.l.
Preparing separation solution, namely taking 25mg of impurity Va-1 reference substance and 25mg of impurity Va-4 reference substance respectively, placing the mixture into a 5ml measuring flask, diluting the mixture to a scale with acetonitrile, and shaking the mixture uniformly to obtain an impurity stock solution. Taking 1.0g of compound (Va), placing into a 10ml measuring flask, adding 1ml of impurity stock solution, diluting to scale with acetonitrile, and shaking to obtain the final product.
1 Μl of the separation solution was precisely measured, injected into a gas chromatograph, and the chromatogram was recorded.
As a result, the retention time of the main peak in the chromatogram of the separation solution was 1.990 minutes, the number of the impurity outlet peaks was less than the number of the added impurities, and the impurities Va-1, va-4 and the unknown peaks were combined to give peaks, the degree of separation between the main peak and the adjacent impurity peaks was 1.38, less than 1.5, and the degree of separation was poor, as shown in FIG. 1.
② The programming temperature was changed to an initial temperature of 50 ℃ for 5 minutes and at a rate of 15 ℃ per minute to 240 ℃ for 8 minutes. The other conditions were the same as those of the condition ①.
1 Μl of the separation solution was precisely measured, injected into a gas chromatograph, and the chromatogram was recorded.
As a result, the separation degree between the peaks of the impurity Va-1 and the impurity Va-4 in the chromatogram of the separation solution was 1.42, less than 1.5, the separation degree was poor, and the tailing factor of the main peak of the compound (Va) was 0.65, less than 1.2, the peak shape was poor, as shown in FIG. 2.
③ Chromatographic column a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane as fixing solution is used as chromatographic column (model DB-624, inner diameter 0.32mm, length 60m, and film thickness 1.8 μm);
Column temperature, which is to raise the temperature to 240 ℃ at a rate of 15 ℃ per minute for 12 minutes, at an initial temperature of 60 ℃ for 2 minutes;
The other conditions were the same as those of the condition ①.
1 Μl of the separation solution was precisely measured, injected into a gas chromatograph, and the chromatogram was recorded.
As a result, the sample solution chromatogram has two main peaks (cis-trans isomers and two main peaks), the minimum theoretical plate number of the main peaks is 818204, the peak shape is good, the minimum separation degree between the main peaks and the adjacent peaks is 4.58 and is more than 1.5, and the separation is good, as shown in figure 3.
Example 2 separation test
The separation test was continued with the chromatographic conditions selected in conditions ③ of example 1.
Preparing impurity locating solution, namely taking methanol, impurity Va-2 reference substance, succinyl aldehyde reference substance, impurity Va-3 reference substance, impurity Va-1 reference substance and impurity Va-4 reference substance respectively by 20mg, placing into 6 10ml measuring flasks, respectively adding acetonitrile for dissolving and diluting to scale, and shaking up to obtain locating solution of each impurity.
The sample solution, the positioning solution and the separation degree solution were measured precisely and 1.0. Mu.l each, and were injected into a gas chromatograph, and the chromatogram was recorded, and the results are shown in Table 1, FIG. 4 and FIG. 5.
The result shows that the butanedial and the impurity Va-3 in the separation degree solution chromatogram have the same peak, the two impurities are combined and controlled in the method, the minimum separation degree between the two main peaks and the adjacent impurity peak is 4.56, the minimum separation degree between the impurity peaks is 5.10, both are more than 1.5, the separation is good, the tailing factor of the main peak in the sample solution chromatogram is 1.04 and less than 2.0, and the method has good specificity.
TABLE 1 positioning and separation test results
Example 3 Linear test
The preparation of the linear solution comprises the steps of taking 1.2g of a compound (Va), precisely weighing, placing in a 10ml measuring flask, adding acetonitrile for dissolution and dilution to a scale, shaking up to obtain a linear solution 1, taking 1.0g of another compound (Va), precisely weighing, placing in a 10ml measuring flask, adding acetonitrile for dissolution and dilution to a scale, shaking up, precisely weighing 5ml, 1ml and 0.1ml of the solution, placing in 310 ml measuring flasks, diluting with acetonitrile to a scale, shaking up to obtain a linear solution 2, a linear solution 3 and a linear solution 4, precisely weighing 0.1ml of the linear solution 3, placing in a 10ml measuring flask, diluting with acetonitrile to a scale, shaking up to obtain a linear solution 5.
Preparing quantitative limiting solution, namely taking 1.0019g of the compound (Va), precisely weighing, placing in a 10ml measuring flask, adding acetonitrile for dissolution and dilution to a scale, shaking uniformly, precisely weighing 0.1ml, placing in the 10ml measuring flask, diluting to the scale with acetonitrile, shaking uniformly, measuring 0.3ml of the sensitive stock solution of the compound (Va), placing in the 10ml measuring flask, diluting to the scale with acetonitrile, and shaking uniformly to obtain the compound (Va).
And precisely measuring 1 mu l of each of the linear solution and the quantitative limiting solution, respectively injecting into a gas chromatograph, recording a chromatogram, taking a curve of peak area versus concentration, and calculating a regression equation and a correlation coefficient by using a least square method, wherein the results are shown in Table 2 and FIG. 6.
TABLE 2 examination of Compound (Va) related substances Linear test results
Example 4 quantitative limit and detection limit
Preparing a sensitive stock solution of the compound (Va), namely taking 1.0019g of the compound (Va), precisely weighing, placing into a 10ml measuring flask, adding acetonitrile for dissolving and diluting to a scale, shaking uniformly, precisely measuring 0.1ml, placing into a 10ml measuring flask, diluting to the scale with acetonitrile, and shaking uniformly.
Preparing quantitative limiting solution of compound (Va), namely weighing 0.3ml of sensitive stock solution of the compound (Va), placing the stock solution into a 10ml measuring flask, diluting to a scale with acetonitrile, and shaking uniformly to obtain the compound (Va).
Preparing a compound (Va) detection limit solution, namely weighing 0.1ml of a compound (Va) sensitivity stock solution, placing the solution into a 10ml measuring flask, diluting to a scale with acetonitrile, and shaking uniformly to obtain the compound (Va).
Preparing impurity stock solution, namely taking 41.8mg of methanol, 38.58mg of impurity Va-2 reference substance, 101.63mg of succinyl aldehyde reference substance, 29.63mg of impurity Va-3 reference substance, 39.98mg of impurity Va-1 reference substance and 40.97mg of impurity Va-4 reference substance, placing the mixture into a 5ml measuring flask, adding acetonitrile solvent, diluting to a scale, shaking up, precisely measuring 1ml, placing the mixture into a 10ml measuring flask, diluting to the scale with acetonitrile, and shaking up.
The impurity stock solution is measured and diluted with acetonitrile to different concentrations, and 1 μl of the impurity stock solution is precisely measured and injected into a gas chromatograph to record a chromatogram. The measured response values are 10 times higher and 3 times higher than the noise signals, namely the quantitative limit and the detection limit of the corresponding compounds, and the results are shown in tables 3, 4 and 7-12.
TABLE 3 quantitative limit results table for examination of Compound (Va) related substances
TABLE 4 examination limit of substances for Compound (Va) results Table
EXAMPLE 5 precision test
The sample solutions were prepared in parallel in 6 parts. 1 μl of each of the single impurities was precisely measured, injected into a gas chromatograph, the chromatogram was recorded, and the detected amounts of the single impurities and the total impurities were analyzed and compared by an area normalization method, the results are shown in Table 5 and FIG. 13, the detected amounts of the single impurities and the total impurities are the same, and the test results of the inspection precision of the substances related to the compound (Va) are good.
TABLE 5 results of Compound (Va) related substance examination precision test
Example 6 stability test
And placing the sample solution under room temperature natural light, precisely measuring 1 μl at 0,2, 4, 6, 8 and 24 hours, injecting into a gas chromatograph, recording a chromatogram, analyzing and comparing the maximum single impurity and the detection amount of total impurities, wherein the result is shown in table 6 and fig. 14, the maximum change rate of the maximum single impurity detection amount is 5.26%, the maximum change rate is less than 20%, the detection amount of total impurities is consistent, no newly added impurities are generated at each time point, and the sample solution is stable within 24 hours.
TABLE 6 test results of stability of examination solution for substances related to Compound (Va)
Example 7 durability test
Based on standard chromatographic conditions, the related substances of the sample are respectively measured by adopting different chromatographic columns, different carrier gas flow rates and different column temperature conditions according to the table 7, 1 μl of the sample solution is precisely measured, the sample solution is injected into a gas chromatograph, the chromatograms are recorded, and the measurement results are compared.
1 Μl of the sample solution is precisely measured, injected into a gas chromatograph, and the chromatogram is recorded, and the results are shown in Table 8 and FIGS. 15-17.
The result shows that the chromatographic columns with the same model and different numbers are used, the carrier gas flow rate is in the range of 0.9-1.1 ml/min, the initial temperature is in the range of 55-65 ℃ and the heating rate is in the range of 12-18 ℃/min, the system applicability results are good, and compared with standard conditions, the maximum variation value of single impurity and total impurity detection quantity is 0.01% at the maximum, so that the durability of the detection method of the related substances of the compound (Va) is good.
TABLE 7 durability of Compound (Va) related substance inspection method
TABLE 8 results of durability test for Compound (Va) related substances
Note that ① samples have cis-trans isomers, and have two main peaks, the theoretical plate number of the main peak is calculated by the minimum value, the tailing factor of the main peak is calculated by the maximum value, and ② is the standard condition.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411754707.1A CN119224184B (en) | 2024-12-03 | 2024-12-03 | A gas chromatography detection method for 2,5-dimethoxytetrahydrofuran related substances |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411754707.1A CN119224184B (en) | 2024-12-03 | 2024-12-03 | A gas chromatography detection method for 2,5-dimethoxytetrahydrofuran related substances |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN119224184A CN119224184A (en) | 2024-12-31 |
| CN119224184B true CN119224184B (en) | 2025-03-25 |
Family
ID=94069029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411754707.1A Active CN119224184B (en) | 2024-12-03 | 2024-12-03 | A gas chromatography detection method for 2,5-dimethoxytetrahydrofuran related substances |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN119224184B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118191134A (en) * | 2024-03-13 | 2024-06-14 | 宿州亿帆药业有限公司 | Method for detecting residual solvent in eptazocine hydrobromide bulk drug |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114563487A (en) * | 2020-11-27 | 2022-05-31 | 杭州中美华东制药有限公司 | A kind of method for determining residual solvent in indobufen bulk drug |
| CN114646694A (en) * | 2020-12-18 | 2022-06-21 | 重庆药友制药有限责任公司 | Method for separating and detecting brexpiprazole impurity by adopting gas chromatography |
| CN114705769B (en) * | 2022-03-04 | 2022-10-28 | 石家庄四药有限公司 | Method for detecting related substances in isopropyl tropine |
| CN114740113B (en) * | 2022-04-12 | 2023-10-20 | 四川汇宇制药股份有限公司 | Separation and detection method for residual solvent and/or related substances in polyacrylic acid |
| CN115636737B (en) * | 2022-09-30 | 2024-02-23 | 洛阳师范学院 | Alkyl functionalized column hexaarene stationary phase, capillary gas chromatographic column, and preparation methods and applications thereof |
| CN115728416B (en) * | 2022-11-15 | 2024-07-12 | 远大生命科学(鞍山)有限公司 | Gas chromatography detection method for 1-bromoethyl acetate and impurities thereof |
| CN117368376A (en) * | 2023-11-21 | 2024-01-09 | 苏州二叶制药有限公司 | Detection method of residual solvent of butylphthalide compound |
| CN118311162A (en) * | 2024-03-19 | 2024-07-09 | 上海司太立制药有限公司 | Gas-phase detection method for (S) - (+) -3-hydroxytetrahydrofuran enantiomer |
-
2024
- 2024-12-03 CN CN202411754707.1A patent/CN119224184B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118191134A (en) * | 2024-03-13 | 2024-06-14 | 宿州亿帆药业有限公司 | Method for detecting residual solvent in eptazocine hydrobromide bulk drug |
Also Published As
| Publication number | Publication date |
|---|---|
| CN119224184A (en) | 2024-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104655751B (en) | A kind of detect the method for organic solvent residual in dapoxetine | |
| CN106645497A (en) | Obeticholic acid and detection method for related substances in preparation of obeticholic acid | |
| CN115453012B (en) | Reversed-phase HPLC method for simultaneously measuring multiple positional isomers in voathixetine hydrobromide | |
| CN119224184B (en) | A gas chromatography detection method for 2,5-dimethoxytetrahydrofuran related substances | |
| CN111679010A (en) | High performance liquid chromatography detection method of remdesivir intermediate GS-441524 | |
| CN109142586B (en) | Method for determining content of atorvastatin calcium intermediate ATS-9 and impurity B thereof by liquid chromatography | |
| CN117647607B (en) | HPLC detection method for simultaneously determining related substances in 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde | |
| CN114778714B (en) | 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl GC-FID purity analysis method | |
| CN113933424B (en) | Method for detecting impurities in apixaban starting material | |
| CN112710762A (en) | Method for measuring residual quantity of dimethyl sulfate | |
| CN115932107B (en) | Method for detecting impurity content in vanillyl ethanone sample | |
| CN115901972B (en) | A chiral chromatographic analysis method for detecting enantiomers | |
| CN114544842A (en) | Method for detecting N-bromosuccinimide in voriconazole | |
| CN114200067B (en) | High performance liquid chromatography analysis method for 6-bromo-3-hydroxy pyrazine-2-carboxamide and impurities | |
| CN116068101B (en) | A method for quantitatively analyzing dimethyl sulfate content by derivatization method | |
| CN115656356B (en) | Determination of 4-hydroxy-7-phenoxyisoquinoline-3-carboxylic acid methyl ester and its related substances | |
| CN115792071B (en) | A method for analyzing related substances of thiocarbamide bromide intermediates | |
| CN114965770B (en) | Method for detecting starting material, impurity D and impurity F in ifosfamide bulk drug | |
| CN109917045A (en) | An HPLC method for the simultaneous determination of the contents of 5 components in Decoction Pieces of Gouji | |
| RU2756549C1 (en) | Method for quantitative determination of the content of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl in the air of the working area by high performance liquid chromatography | |
| CN118759090B (en) | GC-MS method for simultaneously measuring ammonia, dimethylamine and trimethylamine content in methylamine solution | |
| CN112305100B (en) | Method for detecting content of genotoxic impurity benzyl bromide in medicine | |
| CN116297908B (en) | Analysis method of indobufen isomer impurity | |
| CN114324673B (en) | Analysis method for simultaneously determining clemastine fumarate and isomer thereof | |
| CN111103374B (en) | Method for measuring content of 2, 6-tetramethylpiperidine oxide in cinacalcet hydrochloride |
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 |