CN115754042B - Method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide - Google Patents
Method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide Download PDFInfo
- Publication number
- CN115754042B CN115754042B CN202211363858.5A CN202211363858A CN115754042B CN 115754042 B CN115754042 B CN 115754042B CN 202211363858 A CN202211363858 A CN 202211363858A CN 115754042 B CN115754042 B CN 115754042B
- Authority
- CN
- China
- Prior art keywords
- alpha
- impurity
- methyl acetate
- ipratropium bromide
- solution
- 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
Abstract
The invention relates to the technical field of medicine analysis, in particular to a detection method of impurity alpha-formylphenyl methyl acetate in ipratropium bromide. The detection method adopts a liquid chromatography-mass spectrometry to detect the impurity alpha-formylphenyl methyl acetate with lower content in the ipratropium bromide, and can realize the accurate quantification of the impurity alpha-formylphenyl methyl acetate with lower content by adopting specific liquid chromatography conditions and mass spectrometry conditions. The standard curve established by the detection method has good linearity, lower detection limit and quantitative limit and good precision, accuracy and stability, and can be used for quality monitoring in the production process of ipratropium bromide.
Description
Technical Field
The invention relates to the technical field of medicine analysis, in particular to a detection method of impurity alpha-formylphenyl methyl acetate in ipratropium bromide.
Background
The ipratropium bromide has an English name of Ipratropium Bromide, and the name is [ (1R, 5S) -8-methyl-8-isopropyl-8-azabicyclo [3.2.1] oct-3-yl ] 3-hydroxy-2-phenylpropionate bromide or ipratropium bromide, which is a medicament for treating bronchiectasis, can be clinically used for relieving bronchospasm and wheezing symptoms caused by chronic obstructive pulmonary disease and preventing and treating asthma, and is particularly suitable for patients intolerance to the medicament due to muscle tremor and tachycardia caused by using beta receptor agonists. The structural formula is as follows:
however, in the current process for producing ipratropium bromide, a process impurity alpha-formylphenyl methyl acetate is easily remained, and the CAS number is 5894-79-1, and the structural formula is as follows:
according to ICH M7 guidelines, the acceptable limit of impurity alpha-formylphenyl methyl acetate in the ipratropium bromide raw material is 75.0ppm (ng/mg), but the sensitivity of a conventional liquid chromatograph cannot meet the detection requirement of impurity alpha-formylphenyl methyl acetate in the ipratropium bromide raw material, and a detection method capable of accurately determining the content of impurity alpha-formylphenyl methyl acetate with lower concentration in the ipratropium bromide raw material is not found at present.
Disclosure of Invention
In view of the above, an object of the embodiments of the present invention is to provide a method for detecting impurity α -formylphenylacetic acid methyl ester in ipratropium bromide, which can accurately detect impurity α -formylphenylacetic acid methyl ester with low concentration in ipratropium bromide by using a liquid chromatography-mass spectrometry technology.
In order to achieve the above purpose, the embodiment of the invention adopts the following technical scheme:
the method for detecting the impurity alpha-formylphenyl methyl acetate in ipratropium bromide adopts a liquid chromatography-mass spectrometry method to detect the impurity alpha-formylphenyl methyl acetate in ipratropium bromide, and the chromatographic conditions of the liquid chromatography in the liquid chromatography-mass spectrometry method comprise:
chromatographic column: an octadecyl bonded silica gel column,
mobile phase: the mobile phase A is an aqueous solution containing 0.05-0.20% v/v formic acid, the mobile phase B is acetonitrile containing 0.05-0.20% v/v formic acid, and the elution is carried out by adopting a gradient elution mode:
| time min | Mobile phase A% | Mobile phase B% |
| 0.10 | 90 | 10 |
| 2.00 | 90 | 10 |
| 9.00 | 7～13 | 87～93 |
| 15.00 | 7～13 | 87～93 |
| 15.10 | 90 | 10 |
| 17.00 | 90 | 10 |
Total flow rate: 0.55-0.65 mL/min.
According to the invention, specific liquid chromatography conditions are adopted to separate the impurity alpha-formylphenyl methyl acetate from other related substances in the ipratropium bromide raw material, and the liquid chromatograph is combined with a mass spectrometer to realize trace-level detection of the impurity alpha-formylphenyl methyl acetate. The standard curve established by the detection method has good linearity, the linear correlation coefficient can reach 0.995, the recovery rate is between 80% and 120%, the higher accuracy is realized, the detection limit and the quantitative limit are lower, the precision reproducibility is good, and the detection method can accurately quantify the impurity alpha-formylphenylacetic acid methyl ester with trace-level concentration in the ipratropium bromide.
With reference to the first aspect, the specification of the octadecyl bonded silica gel column is: 150X 4.6mm, filler particle size of 5 μm, length of column and size of filler particle size directly affect separation effect of target chromatographic peak.
With reference to the first aspect, the octadecyl bonded silica gel column is model YMC Triart-C18 chromatographic column.
With reference to the first aspect, the column temperature of the chromatographic column is 28-32 ℃, preferably 30 ℃; the flow rate of the mobile phase is 0.60mL/min, and the separation degree of the to-be-detected object is better by selecting proper chromatographic column temperature and the flow rate of the mobile phase, so that the chromatographic peak shape is symmetrical.
With reference to the first aspect, in the method for detecting the impurity α -formyl phenylacetic acid methyl ester in ipratropium bromide, the mass spectrometry conditions in the liquid chromatography-mass spectrometry method include:
ion mode: the positive ion mode of the ESI,
detection mode: the MRM multi-reaction detection is carried out,
air curtain gas: 30 to 40L/min of the total weight of the product,
ionization voltage: 5500-4500V of the total voltage of the power supply,
ionization temperature: 500-600 ℃,
detection ion pair of compound and optimal collision voltage:
ion pairs and collision voltage are key parameters of the detection method, and are directly related to the specificity and response intensity of impurity alpha-formylphenyl methyl acetate in mass spectrum.
With reference to the first aspect, the mass spectrometry conditions in the liquid chromatography-mass spectrometry further include:
collision gas: the Medium (or media) is used to control the processing speed,
cluster removal voltage: 40 to 60V of the total voltage of the electric motor,
injection voltage: 5 to 15V of the total voltage of the power supply,
collision cell ejection voltage: 5 to 15volts of the total weight of the product,
ion source gas: 50 to 60psi of the pressure of the water,
auxiliary heating gas: 50-60 psi.
With reference to the first aspect, the method for detecting the impurity alpha-formylphenyl methyl acetate in ipratropium bromide comprises the following steps: and (3) preparing a standard sample solution, and accurately measuring the content of the impurity alpha-formylphenylacetic acid methyl ester in the ipratropium bromide by using a liquid phase-mass spectrometer and adopting a standard curve method.
And (3) selecting a standard solution with a lower concentration level for measurement and drawing a standard curve, so that the content of the trace-level impurity alpha-formylphenyl methyl acetate can be measured more accurately.
With reference to the first aspect, the method for detecting the impurity alpha-formylphenyl methyl acetate in ipratropium bromide specifically comprises the following steps:
step a, preparing a sample solution and a reference substance solution of the impurity alpha-formylphenyl methyl acetate by taking methanol as a solvent;
step b, determining the reference substance solution by using the liquid chromatography-mass spectrometry, and drawing a standard curve according to the peak area and the concentration of the reference substance solution;
and c, measuring the test solution by using the liquid chromatography-mass spectrometry, and calculating the concentration of the alpha-formylphenyl methyl acetate in the test solution by using the standard curve obtained in the step b.
The solvent methanol is used as a blank solution, and the methanol has no influence on chromatographic peaks of impurity alpha-formylphenyl methyl acetate and can well dissolve a test sample.
With reference to the first aspect, the concentration of the reference solution ranges from 0.050 to 1.50 μg/ml, and when the concentration of the reference solution is measured in the concentration range, the concentration of the alpha-formylphenyl methyl acetate has an optimal linear relation with the mass spectrum peak area.
In a second aspect, the application of a detection method for impurity alpha-formylphenyl methyl acetate in ipratropium bromide can realize accurate quantification of impurity alpha-formylphenyl methyl acetate in ipratropium bromide.
The invention has the beneficial effects that: the liquid chromatography-mass spectrometry has the advantages of strong specificity, good linear relation, high sensitivity, accurate and reliable quantification, and good precision and durability, and can be used for trace detection of alpha-formylphenylacetic acid methyl ester as a potential process impurity in the ipratropium bromide raw material, and used as a basis for monitoring the quality of the ipratropium bromide raw material.
Drawings
FIG. 1 is a standard curve of impurity alpha-formylphenyl methyl acetate control solution;
FIG. 2 is a mass spectrum of a methanol blank solution;
FIG. 3 is a mass spectrum of impurity alpha-formylphenyl methyl acetate control solution;
FIG. 4 is a mass spectrum of a sample solution of impurity methyl-formylphenylacetate;
FIG. 5 is a mass spectrum of a mixed solution of an impurity of alpha-formylphenyl methyl acetate as a control and a test sample.
Detailed Description
The present invention will be described in further detail below in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
In the following examples:
alpha-formylphenylacetic acid methyl ester is purchased from the apo-chemical engineering (Shanghai) limited company and has a purity of 97.9%;
the mass spectrometer was a 4000QTRAP mass spectrometer manufactured by AB SCIEX.
Example 1
The embodiment of the invention provides a method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide, which comprises the steps of preparing a reference substance solution and a test substance solution by taking methanol as a solvent, and measuring by using a liquid chromatography-mass spectrometry.
1. The measurement conditions of the liquid chromatograph are:
chromatographic column: YMC Triart-C18 (4.6mm.times.150mm, filler particle size 5 μm),
mobile phase: mobile phase a was an aqueous solution containing 0.10% formic acid, mobile phase B was acetonitrile containing 0.10% formic acid, gradient elution conditions:
| time min | Mobile phase A% | Mobile phase B% |
| 0.10 | 90 | 10 |
| 2.00 | 90 | 10 |
| 9.00 | 10 | 90 |
| 15.00 | 10 | 90 |
| 15.10 | 90 | 10 |
| 17.00 | 90 | 10 |
Total flow rate: the concentration of the solution is 0.60mL/min,
column temperature: 30 ℃,
sample injection volume: 10 mu L.
2. The measurement conditions of the mass spectrometer are as follows:
ion mode: the positive ion mode of the ESI,
detection mode: the MRM multi-reaction detection is carried out,
air curtain gas: the concentration of the solution is 35L/min,
collision gas: the Medium (or media) is used to control the processing speed,
cluster removal voltage: the voltage of the air is 50V, and the air is heated,
injection voltage: the voltage of the steel is 10V,
collision cell ejection voltage: the temperature of the liquid is 10volts, and the temperature of the liquid is 10volts,
ionization voltage: the temperature of the air is 5000V,
ion source gas: 55psi of the total pressure of the mixture,
auxiliary heating gas: 55psi of the total pressure of the mixture,
ionization temperature: 550 c,
detection ion pair of compound and optimal collision voltage:
3. preparing a control solution and a test sample solution:
(1) Control stock solution: weighing a proper amount of impurity alpha-formylphenyl methyl acetate, precisely weighing, and preparing a solution containing about 15 mug of impurity alpha-formylphenyl methyl acetate per 1mL by using methanol as a reference substance stock solution for later use;
(2) Control solution: precisely transferring 0.5mL of the reference substance stock solution into a 10mL volumetric flask, and diluting with methanol to scale to obtain reference substance solution;
(3) Test solution: weighing about 100mg of a test sample, precisely weighing, placing in a 10mL volumetric flask, and diluting with methanol to scale to obtain a test sample solution for later use;
(4) Control solution + test solution: precisely transferring 0.5mL of reference stock solution, precisely weighing about 100mg of test sample, placing into a 10mL volumetric flask, and diluting with methanol to scale to obtain reference solution and test sample solution.
4. And (3) methodological verification:
(1) Specialization of
In order to determine the peak time of impurity alpha-formylphenyl methyl acetate under the measuring conditions of the method, the prepared reference substance solution and the prepared sample solution are sequentially detected according to the liquid chromatography and mass spectrum conditions, and the detection results are sequentially shown in figures 2-5. The mass spectrum obtained by analyzing the detection result can be shown as follows: the methanol is taken as a blank solution and other components in the test sample, so that the determination of the impurity alpha-formylphenyl methyl acetate is not interfered, and the impurity alpha-formylphenyl methyl acetate can be normally detected in the test sample, which proves that the determination method provided by the invention can realize qualitative detection of the impurity alpha-formylphenyl methyl acetate.
(2) Linear validation
A certain amount of alpha-formylphenyl methyl acetate is weighed, precisely weighed, dissolved by methanol and fixed in volume, and a series of standard solutions of about 75ng, 150ng, 300ng, 600ng, 750ng, 1200ng and 1500ng in each 1ml are prepared. The detection was performed according to the above conditions of liquid chromatography and mass spectrometry, and the detection results are shown in table 1. And drawing a standard curve by taking the concentration (ng/mL) of the alpha-formylphenyl acetic acid methyl ester as an abscissa and the area of a mass spectrum peak as an ordinate, and calculating a regression equation. The standard curve is shown in fig. 1, and the linear regression equation is: y= 328.59x-420.65, and the linear correlation coefficient r= 0.9958.
TABLE 1 Linear test results
(3) Detection limit
Measuring a certain volume of the reference substance solution, gradually and quantitatively diluting with methanol, and detecting according to the conditions of liquid chromatography and mass spectrometry. After detection, the detection limit of the solution is 37.59ng/ml according to the signal-to-noise ratio not lower than 3:1, and the detection limit of the solution is 0.376ng/mg after conversion into the test sample.
(4) Quantitative limit
Measuring a certain volume of the reference substance solution, gradually and quantitatively diluting with methanol, and detecting according to the conditions of liquid chromatography and mass spectrometry. The detection shows that the quantitative limit of the solution is 75.17ng/ml according to the signal to noise ratio not lower than 10:1, and the quantitative limit of the solution is 0.752ng/mg after being converted into the test sample.
6 parts of quantitative limit concentration solutions (solution 1 to solution 6) were prepared in parallel, and the 6 parts of solutions were detected according to the above conditions of liquid chromatography and mass spectrometry, and the quantitative limit precision was analyzed, and the results are shown in Table 2.
TABLE 2 quantitative limit concentration solution reproducibility test results
As can be seen from Table 1, the relative standard deviation of the above 6 parallel determinations is 5.64%, which meets the detection requirements, and shows that the quantitative determination of trace level of impurity alpha-formylphenylacetic acid methyl ester can be realized by adopting the liquid chromatography and mass spectrometry combined technology.
(5) Repeatability of
The sample solution was measured, 6 parallel samples (1 to 6) were prepared, and the 6 parallel samples were examined under the conditions of liquid chromatography and mass spectrometry, and the examination results are shown in Table 3.
TABLE 3 repeatability test results
As shown in the test results of Table 3, the results of the 6 parallel test solutions were all undetected, indicating that the reproducibility of the test method of the present invention was good.
(6) Precision of
The control solution was measured, 6 parallel samples (1 to 6) were prepared, and the 6 parallel samples were examined under the conditions of liquid chromatography and mass spectrometry, and the examination results are shown in Table 4.
TABLE 4 precision measurement results
As shown in the test results of Table 4, the relative standard deviation of the peak areas corresponding to 6 parallel reference solutions is 2.49%, and the requirement that the relative standard deviation of the precision in the field is smaller than or equal to 10% is met, which indicates that the precision of the test method of the invention is good.
(7) Accuracy of
The accuracy test of impurity α -formylphenylacetic acid methyl ester is expressed as the following recovery (%).
The preparation method comprises the steps of respectively measuring different volumes of the reference substance solutions according to the following preparation method, respectively mixing the reference substance solutions with a certain amount of test substances, and preparing to obtain three different concentration test substance labeling solutions of low concentration labeling, medium concentration labeling and high concentration labeling, wherein the specific preparation method is as follows:
low concentration addition of the standard solution (80% limit recovery solution): accurately transferring 0.4mL of the reference substance stock solution into a 10mL volumetric flask, adding about 10mg of the test substance, diluting to scale with methanol, and preparing three parts in parallel;
medium concentration standard adding solution (100% limit recovery solution): accurately transferring 0.5mL of the reference substance stock solution into a 10mL volumetric flask, adding about 10mg of the test substance, diluting to scale with methanol, and preparing three parts in parallel;
high concentration labeling solution (160% limit recovery solution): accurately transferring 0.8mL of the reference substance stock solution into a 10mL volumetric flask, adding about 10mg of the test substance, diluting to scale with methanol, and preparing three parts in parallel.
Detecting the labeling solutions of the three samples with different concentrations according to the conditions of the liquid chromatography and the mass spectrum, wherein the detection results are shown in a table 5, and the labeling recovery rates are respectively calculated according to the formula: the addition recovery (%) = (recovery amount-background amount)/addition amount×100%.
TABLE 5 accuracy test results
As shown in the results of Table 5, the impurity alpha-formylphenyl methyl acetate was in the range of 80% -160% of the limit concentration, and the recovery rate was 91.85% -94.79%, which indicates that the detection method of the present invention has good accuracy.
Example 2
The embodiment of the invention provides a detection method of impurity alpha-formylphenyl methyl acetate in ipratropium bromide, which mainly examines the durability of the detection method to impurity alpha-formylphenyl methyl acetate.
The chromatographic conditions in example 1 were subjected to fine adjustment in terms of flow rate, column temperature and mobile phase, and the control solutions were each examined according to the detection conditions after fine adjustment, and the detection results are shown in table 6.
TABLE 6 durability test results
As is clear from Table 6, the chromatographic conditions of the fine-tuning liquid chromatograph have substantially no influence on the detection of impurity alpha-formylphenyl methyl acetate, indicating that the detection method has good durability.
Example 3
The embodiment of the invention provides a detection method of impurity alpha-formylphenyl methyl acetate in ipratropium bromide, which mainly examines the intermediate precision of the detection method, namely the detection dates of the repeated detection of the embodiment and the embodiment 1 (5) are different, the detection personnel are different, but the conditions of liquid chromatography and mass spectrum are the same as the embodiment 1.
The sample solution was measured, 6 parallel samples were prepared, and the 6 parallel samples were tested under the same test conditions as in example 1, and the test results are shown in Table 7.
TABLE 7 intermediate precision test results
As is clear from Table 7, the results of the detection of 6 parallel samples prepared from the sample solution were all undetected, and they were consistent with the results of the repeated detection in example 1 (5), indicating that the intermediate precision of the detection method was good.
Example 4
The embodiment of the invention provides a detection method of impurity alpha-formylphenyl methyl acetate in ipratropium bromide, and the embodiment mainly examines the stability of a solution used in the detection method.
The above reference solution and the test solution were left standing at room temperature, and were detected at intervals of 0h, 2h, 4h, 6h, 8h and 24h according to the detection conditions in example 1, and the detection results of the reference solution and the test solution after different standing times are shown in tables 10 and 11, respectively.
Table 10 results of stability test of control solution
TABLE 11 test sample solution stability test results
As can be seen from the detection results in Table 10, the reference substance solution is kept stand for 0 to 24 hours at room temperature, and the relative standard deviation of the mass spectrum peak areas of the alpha-formylphenyl methyl acetate kept stand for different times is 5.69 percent, so that the requirements of less than or equal to 10 percent are met; as can be seen from the detection results in Table 11, the test solution is kept stand for 0 to 24 hours at room temperature, and the detection results of the alpha-formylphenyl methyl acetate in the test solution which is kept stand for different times are all undetected; the test results in tables 10 and 11 show that the solutions used in the test methods have good stability.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (9)
1. The method for detecting the impurity alpha-formylphenyl methyl acetate in ipratropium bromide is characterized by detecting the impurity alpha-formylphenyl methyl acetate in ipratropium bromide by using a liquid chromatography-mass spectrometry, wherein chromatographic conditions of liquid chromatography in the liquid chromatography-mass spectrometry comprise:
chromatographic column: an octadecyl bonded silica gel column,
mobile phase: the mobile phase A is an aqueous solution containing 0.05-0.20% v/v formic acid, the mobile phase B is acetonitrile containing 0.05-0.20% v/v formic acid, and the elution is carried out by adopting a gradient elution mode:
total flow rate: 0.55-0.65 mL/min;
the mass spectrum conditions in the liquid chromatography-mass spectrometry method comprise:
ion mode: the positive ion mode of the ESI,
detection mode: the MRM multi-reaction detection is carried out,
air curtain gas: 30 to 40L/min,
ionization voltage: 5500 to 4500v of the total voltage of the battery,
ionization temperature: 500-600 ℃,
detection ion pair of compound and optimal collision voltage:
2. the method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide according to claim 1, wherein said octadecyl bonded silica gel column has the following specification: 150X 4.6mm, filler particle size 5 μm.
3. The method for detecting alpha-formylphenylacetic acid methyl ester impurity in ipratropium bromide according to claim 1, wherein said octadecyl bonded silica gel column is model number YMC Triart-C18 chromatographic column.
4. The method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide according to claim 1, wherein the chromatographic column temperature is 28-32 ℃; and/or
The mobile phase flow rate was 0.60mL/min.
5. The method for detecting alpha-formylphenylacetic acid methyl ester as defined in claim 1, wherein the mass spectrometry conditions in the liquid chromatography-mass spectrometry further comprise:
collision gas: the Medium (or media) is used to control the processing speed,
cluster removal voltage: 40 to 60V of the total voltage of the power supply,
injection voltage: 5 to 15V of the total voltage of the power supply,
collision cell ejection voltage: 5 to 15volts of the total content of the product,
ion source gas: 50 to 60psi of the pressure of the oil,
auxiliary heating gas: 50-60 psi.
6. The method for detecting alpha-formylphenyl methyl acetate as an impurity in ipratropium bromide according to any one of claims 1-5, comprising the steps of: preparing a control solution and a sample solution of a sample to be detected of ipratropium bromide, and detecting impurity alpha-formylphenylacetic acid methyl ester in the sample solution of the sample to be detected of ipratropium bromide by adopting a liquid chromatography-mass spectrometry method through a standard curve method.
7. The method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide according to claim 6, comprising the following steps:
step a, preparing a sample solution and a reference substance solution of the impurity alpha-formylphenyl methyl acetate by taking methanol as a solvent;
step b, determining the reference substance solution by using the liquid chromatography-mass spectrometry, and drawing a standard curve according to the peak area and the concentration of the reference substance solution;
and c, measuring the test solution by using the liquid chromatography-mass spectrometry, and calculating the concentration of the alpha-formylphenyl methyl acetate in the test solution by using the standard curve obtained in the step b.
8. The method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide according to claim 7, wherein said reference solution concentration range is 0.050-1.50 μg/ml.
9. Use of the method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide according to any one of claims 1-8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211363858.5A CN115754042B (en) | 2022-11-02 | 2022-11-02 | Method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211363858.5A CN115754042B (en) | 2022-11-02 | 2022-11-02 | Method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115754042A CN115754042A (en) | 2023-03-07 |
| CN115754042B true CN115754042B (en) | 2023-06-09 |
Family
ID=85355513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211363858.5A Active CN115754042B (en) | 2022-11-02 | 2022-11-02 | Method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115754042B (en) |
-
2022
- 2022-11-02 CN CN202211363858.5A patent/CN115754042B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN115754042A (en) | 2023-03-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114460188A (en) | Kit for detecting human plasma catecholamine intermediate metabolite and testing method | |
| CN112697933A (en) | Method for measuring content of hydroxypropyl tetrahydropyrane triol and diastereoisomer ratio thereof | |
| CN115754042B (en) | Method for detecting impurity alpha-formylphenyl methyl acetate in ipratropium bromide | |
| CN112098527B (en) | Detection method of ticagrelor starting material | |
| CN115097023B (en) | High performance liquid chromatography detection method for zomib amine related substances | |
| CN112611813B (en) | Method for testing genotoxic impurities of Sacubitril valsartan sodium starting material | |
| CN113588837B (en) | Detection method of moxifloxacin hydrochloride related substance | |
| CN111595961B (en) | Detection method of vitamin B2 related substances | |
| CN110836930A (en) | Method for measuring content of dichlorobutane in levetiracetam by gas chromatography-mass spectrometry | |
| CN114689737A (en) | Analysis method of S-o-chlorophenyl glycine methyl ester tartrate related substances | |
| CN114660183A (en) | High performance liquid chromatography analysis method for separating and measuring L-alanine isopropyl ester hydrochloride enantiomer | |
| CN113777204B (en) | Detection method of p-hydroxyacetophenone related substances | |
| CN115963217B (en) | Detection method of imidapril intermediate and impurity | |
| CN111624276B (en) | Method for simultaneously detecting genotoxic impurities 5-isoquinoline methyl sulfonate and 5-isoquinoline ethyl sulfonate in fasudil hydrochloride | |
| CN115015457B (en) | Method for analyzing bromoacetic acid impurity in selapage by high performance liquid chromatography | |
| CN117191997A (en) | Analytical method for quantitatively detecting alpha-phenethylamine content in pitavastatin calcium | |
| CN112986449A (en) | Method for detecting 2-amino-5-nitrothiazole genotoxic impurities in nitazoxanide | |
| CN114705790B (en) | Detection method of ethyl (2R, 4R) -4-methyl-2-piperidinecarboxylate isomer | |
| CN114088830B (en) | Method for detecting isomer in 4- (3-fluorobenzyloxy) benzaldehyde | |
| CN114935615B (en) | Method for detecting 2-methylimidazole impurity in metronidazole raw material | |
| CN112034058B (en) | Method for detecting isomer impurities in vincamine | |
| CN116879428B (en) | High performance liquid analysis method for residual content of phosphorylcholine in L-alpha-phosphorylcholine | |
| CN114200067B (en) | High performance liquid chromatography analysis method for 6-bromo-3-hydroxy pyrazine-2-carboxamide and impurities | |
| CN117990817A (en) | Method for measuring impurity content in pharmaceutical intermediate acyl chloride iminodibenzyl by utilizing HPLC | |
| CN112986405A (en) | Ultra-high performance liquid phase fingerprint detection method for traditional Chinese medicine injection |
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 |