CN112067733B - Method for detecting trifluoroacetic acid in vildagliptin - Google Patents
Method for detecting trifluoroacetic acid in vildagliptin Download PDFInfo
- Publication number
- CN112067733B CN112067733B CN202010806723.6A CN202010806723A CN112067733B CN 112067733 B CN112067733 B CN 112067733B CN 202010806723 A CN202010806723 A CN 202010806723A CN 112067733 B CN112067733 B CN 112067733B
- Authority
- CN
- China
- Prior art keywords
- vildagliptin
- trifluoroacetic acid
- column
- detecting
- detection
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/64—Electrical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—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
- G01N30/96—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 using ion-exchange
-
- 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
- G01N2030/645—Electrical detectors electrical conductivity 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for detecting trifluoroacetic acid in vildagliptin, belonging to the technical field of chemical substance detection. The detection method has strong specificity and high sensitivity, the trifluoroacetic acid and other components in the sample can be well separated, the linear relation (r = 0.9975) is good in the range of 0.25-7.56 mu g/mL, the detection limit is 1ng/mL, and the quantification limit is 5ng/mL; the detection method can be used as an effective detection method for trifluoroacetic acid in vildagliptin.
Description
Technical Field
The invention relates to detection of impurities in a medicine, in particular to detection of trifluoroacetic acid impurities in vildagliptin, and belongs to the technical field of chemical substance detection.
Background
Vildagliptin is a hypoglycemic drug and can effectively control the content of blood sugar of patients with type 2 diabetes. Trifluoroacetic acid impurities are easily introduced in the synthesis process of vildagliptin, and trifluoroacetic acid has certain toxicity in clinic and the content of trifluoroacetic acid needs to be controlled. At present, some pharmaceutical enterprises in China adopt liquid chromatography to detect and control the content of trifluoroacetic acid, however, the response value of trifluoroacetic acid in liquid phase is extremely low, and the content of trifluoroacetic acid is difficult to accurately determine by adopting liquid chromatography.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a method for detecting trifluoroacetic acid in vildagliptin, so that the separation degree of the trifluoroacetic acid and other components in vildagliptin samples is improved, and the accuracy of trifluoroacetic acid detection is improved.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a method for detecting trifluoroacetic acid in vildagliptin adopts ion chromatography for detection.
The technical scheme of the invention is further improved in that the method comprises the following steps: firstly, carrying vildagliptin into a protective column of an ion chromatographic column by using leacheate, conveying the vildagliptin into an analytical column of the ion chromatographic column after the vildagliptin is treated by the protective column, treating the vildagliptin in the analytical column after the vildagliptin is treated by the protective column, and carrying out conductivity detection by a conductivity detector after the vildagliptin is treated by an inhibitor; the leacheate is a sodium hydroxide solution.
The technical scheme of the invention is further improved as follows: the ion chromatographic column is a DIonex Ionpac AS22 anion exchange chromatographic column with the specification of 4mm multiplied by 250mm; the protective column is an Ionpac AG22 chromatographic column, and the specification is 4mm multiplied by 50mm.
The technical scheme of the invention is further improved as follows: the eluent is sodium hydroxide solution with the concentration of 7-8 mmol/L, and the flow rate of the eluent is 0.95-1.05 ml/min.
The technical scheme of the invention is further improved as follows: the eluent is sodium hydroxide solution with the concentration of 7.5mmol/L, and the flow rate of the eluent is 1.00ml/min.
The technical scheme of the invention is further improved as follows: the temperature of the conductivity cell in the conductivity detection process of the conductivity detector is 34-36 ℃.
The technical scheme of the invention is further improved as follows: the temperature of the conductivity cell in the conductivity detection process of the conductivity detector is 35 ℃.
The technical scheme of the invention is further improved as follows: the temperature of the ion chromatographic column is 30 ℃ in the using process, and the sample injection amount is 10 mu L in the detection of the ion chromatographic method.
The technical scheme of the invention is further improved as follows: and further comprises the step of adding water to the vildagliptin for dissolving and diluting, and then adding the vildagliptin into a protective column of the ion chromatographic column.
The technical scheme of the invention is further improved as follows: the detection limit of the trifluoroacetic acid in the method is 1ng/ml, and the quantification limit is 5ng/ml.
Due to the adoption of the technical scheme, the invention has the technical progress that:
the detection method disclosed by the invention is strong in specificity and high in sensitivity, trifluoroacetic acid and other components in a sample can be well separated, a good linear relation (r = 0.9975) is realized in a range of 0.25-7.56 mug/mL, the detection limit is 1ng/mL, and the quantification limit is 5ng/mL; the linearity and accuracy of the detection method can meet the requirement of quantitative test, and the detection result of the method is accurate and reliable and can be used as an effective method for detecting trifluoroacetic acid in vildagliptin.
According to the detection method, a sodium hydroxide solution with the concentration of about 7.5mmol/L is used as the leacheate, trifluoroacetic acid cannot be well separated from other components in vildagliptin when the concentration of the sodium hydroxide solution is too low, the precision of the area of the peak of the trifluoroacetic acid is reduced during chromatographic detection when the concentration of the sodium hydroxide solution is too high, and the leacheate with too high concentration can obstruct an ion exchange process between a mobile phase and an ion exchange group bonded on a matrix.
Drawings
FIG. 1 is a chromatogram of a trifluoroacetic acid control solution according to an example of the invention;
FIG. 2 is a chromatogram of a test solution in an example of the present invention.
Detailed Description
The present invention is further illustrated in detail below with reference to examples:
a method for detecting trifluoroacetic acid in vildagliptin adopts ion chromatography for detection, and specifically comprises the following steps: firstly, carrying vildagliptin into a protective column of an ion chromatographic column by using leacheate, conveying the vildagliptin into an analytical column of the ion chromatographic column after the vildagliptin is treated by the protective column, treating the vildagliptin in the analytical column after the vildagliptin is treated by the protective column, and carrying out conductivity detection by a conductivity detector after the vildagliptin is treated by an inhibitor; the leacheate is a sodium hydroxide solution.
Wherein, the preferable ion chromatographic column is a Dionex Ionpac AS22 anion exchange chromatographic column with the specification of 4mm multiplied by 250mm; the protective column is an Ionpac AG22 chromatographic column, and the specification is 4mm multiplied by 50mm; the leacheate is a sodium hydroxide solution with the concentration of 7-8 mmol/L, the flow rate of the leacheate is 0.95-1.05 ml/min, the leacheate is preferably a sodium hydroxide solution with the concentration of 7.5mmol/L, and the flow rate of the leacheate is 1.00ml/min; preferably, the temperature of the conductance cell in the conductance detection process of the conductance detector is 34-36 ℃, and further preferably, the temperature of the conductance cell in the conductance detection process of the conductance detector is 35 ℃; the temperature of the ion chromatographic column is 30 ℃ in the using process, and the sample injection amount is 10 mu L in the detection of the ion chromatographic method.
Preferably, the detection method further comprises the step of adding water to dissolve and dilute vildagliptin, and then adding the vildagliptin into a protective column of the ion chromatographic column. The detection limit of the trifluoroacetic acid in the method is 1ng/ml, and the quantification limit is 5ng/ml.
Examples
1 instruments and reagents
1.1 Instrument ion chromatograph (Dionex AQUION, chromeleon workstation), electronic balance (Mettler-Tollido, XS 105).
1.2 reagent trifluoroacetic acid reference (AR, allantin, lot number 11620036); sodium hydroxide (GR, tianjin Yongda chemical reagents, inc., batch number 20181031); vildagliptin samples (Zhejiang, meinuohua pharmaceutical chemistry, inc., lot number: VGT-3-181102); water for injection (home made).
2 detection step
2.1 chromatographic conditions ion chromatography: dionex aquaion; a detector: a conductance detector; column temperature: 30 ℃; temperature of the conductivity cell: 35 ℃; a suppressor: an anion suppressor; and (3) chromatographic column: anion exchange chromatography column (Dionex Ionpac As22,4 mm. Times.250 mm); flow rate: 1.0ml/min; leacheate: every 1000ml of water contains 7.5mmol of sodium hydroxide; diluent agent: water; sample introduction amount: 10 μ L.
2.2 preparation of solution control solution: taking about 50mg of trifluoroacetic acid reference substance, placing in a 100ml measuring flask, adding water to dissolve and dilute to the scale, shaking uniformly, precisely measuring 1ml, placing in a 100ml measuring flask, adding water to dilute to the scale, and shaking uniformly.
Test solution: weighing about 38.4mg of vildagliptin, precisely weighing, placing in a 10mL volumetric flask, adding water to dissolve and dilute to a scale, and shaking up to obtain a test solution.
3 results of detection
3.1 preparing 7.5mmol/L sodium hydroxide leacheate, taking trifluoroacetic acid reference solution, injecting the trifluoroacetic acid reference solution into an ion chromatograph according to the chromatography method of the part 2.1, and recording a chromatogram. The sample introduction was repeated 6 times, and the retention time of the trifluoroacetic acid peak and the RSD of the peak area are shown in Table 1.
TABLE 1
3.2 System applicability test trifluoroacetic acid as reference solution and test solution are injected into ion chromatograph according to the chromatography method of part 2.1, and chromatogram is recorded. The retention time of trifluoroacetic acid is about 7.8min, the separation degree of the trifluoroacetic acid peak and the unknown impurity peak in the reference substance spectrum is 4.55 (shown in figure 1), the separation degree of the trifluoroacetic acid peak and the unknown impurity peak in the sample spectrum is 4.59, and the trifluoroacetic acid peak and other impurity peaks can be effectively separated (shown in figure 2).
3.3 precision trifluoroacetic acid control solution was injected into ion chromatograph according to the above 2.1 part of chromatography method, and chromatogram was recorded. The sample introduction was repeated 6 times, and the retention time of the trifluoroacetic acid peak and the RSD of the peak area were 0.07% and 1.49%, respectively.
3.4 limits of detection and quantitation trifluoroacetic acid controls were diluted with water to make solutions containing 5ng/mL trifluoroacetic acid per 1mL, injected into an ion chromatograph according to the chromatography method described above for section 2.1, and chromatograms were recorded, with trifluoroacetic acid detection limit of 1ng/mL, calculated as S/N =3, and quantitation limit of 5ng/mL, calculated as S/N = 10.
3.5 Linear in the predetermined 0.25 ~ g/mL ~ 7.56 ~ g/mL, i.e. impurity limit of 5% -150% concentration range, respectively preparation of 5% (0.25 ~ g/mL), limit 10% (0.50 ~ g/mL), limit 25% (1.26 ~ g/mL), limit 50% (2.52 ~ g/mL), limit 75% (3.78 ~ g/mL), limit 100% (5.04 ~ g/mL), limit 150% (7.56 ~ g/mL) 7 concentration solution. Injecting into ion chromatograph according to the chromatography method of part 2.1, recording chromatogram, and calculating regression equation and regression coefficient by taking peak area versus concentration as curve. The linear regression equation was y =7.6466X-1.4515 with a correlation coefficient of 0.9975.
3.6 repeatedly weighing a proper amount of sample, adding a solvent to dilute the sample into a solution of 3.84mg/ml, preparing 6 parts in parallel, respectively taking 50.3mg and 49.7mg of trifluoroacetic acid reference substances, respectively placing the reference substances into a 100ml measuring flask, adding water to dissolve the reference substances and diluting the reference substances to a scale, shaking up, respectively precisely measuring 1ml, placing the reference substances into the 100ml measuring flask, adding water to dilute the reference substances to the scale, shaking up to obtain 2 parts of parallel reference solution, and injecting the sample according to the chromatographic conditions of the 2.1 parts, wherein the results are shown in Table 2.
TABLE 2
3.6 recovery rate, precisely weighing a proper amount of trifluoroacetic acid reference substance, preparing 3 solutions with different concentrations, and preparing 3 parts of each concentration. Separately adding vildagliptin samples into the 3 solutions with different concentrations, respectively carrying out experiments according to the chromatographic conditions of the 2.1 parts, and calculating the recovery rate range of the trifluoroacetic acid by an external standard method to be 93.3-111.8%, wherein the results are shown in table 3.
TABLE 3
Comparative example 1
Comparative example 1 is a comparative test of the above examples except that the content of trifluoroacetic acid in vildagliptin is measured by high performance liquid chromatography in comparative example 1. Comparative experiment the samples tested were vildagliptin sample 1 lot (manufacturer: zhejiang melanowa pharmaceutical chemistry, ltd.: lot: VGT-3-181102), and the test results are shown in Table 5.
The specific operation steps of the high performance liquid chromatography are as follows:
taking a proper amount of the product, precisely weighing, dissolving by using a mobile phase A, and quantitatively diluting to prepare a solution containing 10mg of the product in each 1ml, wherein the solution is used as a test solution; in addition, a proper amount of a trifluoroacetic acid reference substance is precisely measured, precisely weighed and quantitatively diluted by a mobile phase A to prepare a solution containing about 13 mu g of trifluoroacetic acid in each 1ml of trifluoroacetic acid reference substance as a reference substance solution. Performing high performance liquid chromatography test with octadecylsilane chemically bonded silica as filler (Innoval ODS-2.6X 250mm,5 μm or equivalent chromatographic column); taking a phosphoric acid solution (0.7 mL of phosphoric acid is precisely measured, adding water to dilute to 1000mL, adjusting the pH to 3.0 by using a 10% sodium hydroxide solution), taking methanol (98; linear gradient elution was performed as in table 4 below; the flow rate was 1.0ml per minute; the column temperature was 25 ℃; the detection wavelength was 210nm. Respectively and precisely weighing appropriate amount of vildagliptin and trifluoroacetic acid reference substances, adding a solvent for dissolving, and quantitatively diluting to prepare a mixed solution containing 10mg of vildagliptin and 13 mu g of trifluoroacetic acid in each 1ml, taking the mixed solution as a system applicability solution, precisely measuring 10ul of the mixed solution, injecting the mixed solution into a liquid chromatograph, recording a chromatogram, and ensuring that the separation degree between a trifluoroacetic acid peak and a main component peak meets the requirement. And precisely measuring 10ul of each of the test solution and the reference solution, respectively injecting into a liquid chromatograph, recording a chromatogram, and calculating peak area according to an external standard method if a chromatographic peak consistent with the retention time of the trifluoroacetic acid peak exists in the chromatogram of the test solution.
TABLE 4
TABLE 5
As can be seen from the above table, ion chromatography has higher detection sensitivity than high performance liquid chromatography.
Comparative examples 2, 3 and 4
Comparative examples 2, 3 and 4 are comparative tests of the above examples, except that the eluent in comparative example 2 was a sodium hydroxide solution having a concentration of 5mmol/L, the eluent in comparative example 3 was a sodium hydroxide solution having a concentration of 10mmol/L, the eluent in comparative example 4 was a sodium hydroxide solution having a concentration of 15mmol/L, the remaining operational steps and parameters were the same as in the examples, and the samples were also repeated 6 times for each comparative test, and the peak retention time of trifluoroacetic acid and the RSD of the peak area are shown in Table 6.
TABLE 6
As can be seen from Table 6, as the concentration of the sodium hydroxide leacheate increased, the retention time was advanced and the peak area decreased. When the sodium hydroxide leacheate concentration was increased to 15mmol/L, the RSD was 6.19%, over 2%.
Comparative example 5
Comparative example 5 is a comparative test of an example, and is different in that the leacheate of the comparative example 5 is a mixed solution of sodium carbonate and sodium bicarbonate, the volume concentration of the mixed solution is 2%, the volume ratio of the sodium carbonate to the sodium bicarbonate in the mixed solution is 7, and the rest parameters are the same as the parameters of the example, so that the trifluoroacetic acid peak in the comparative example 5 cannot be separated from other components in vildagliptin, the peaks are staggered with each other, and the content detection of the trifluoroacetic acid cannot be realized.
Claims (6)
1. A method for detecting trifluoroacetic acid in vildagliptin is characterized by comprising the following steps: detecting by ion chromatography;
the method comprises the following steps: firstly, carrying vildagliptin into a protective column of an ion chromatographic column by using leacheate, conveying the vildagliptin into an analytical column of the ion chromatographic column after the vildagliptin is treated by the protective column, treating the vildagliptin in the analytical column after the vildagliptin is treated by the protective column, and then carrying out conductivity detection by a conductivity detector after the vildagliptin is treated by an inhibitor; the leacheate is a sodium hydroxide solution;
the ion chromatographic column is a DIonex Ionpac AS22 anion exchange chromatographic column with the specification of 4mm multiplied by 250mm; the protective column is an Ionpac AG22 chromatographic column, and the specification is 4mm multiplied by 50mm;
the temperature of the conductance cell is 34-36 ℃ in the process of conducting conductance detection by the conductance detector;
the eluent is a sodium hydroxide solution with the concentration of 7-8 mmol/L, and the flow rate of the eluent is 0.95-1.05 ml/min;
the vildagliptin is a test solution, and the preparation method comprises the following steps: weighing about 38.4mg of vildagliptin, precisely weighing, placing in a 10mL volumetric flask, adding water to dissolve and dilute to a scale, and shaking up.
2. The method for detecting trifluoroacetic acid in vildagliptin according to claim 1, wherein the method comprises the following steps: the eluent is a sodium hydroxide solution with the concentration of 7.5mmol/L, and the flow rate of the eluent is 1.00ml/min.
3. The method for detecting trifluoroacetic acid in vildagliptin according to claim 1, wherein the method comprises the following steps: the temperature of the conductivity cell in the conductivity detection process of the conductivity detector is 35 ℃.
4. The method for detecting trifluoroacetic acid in vildagliptin according to claim 1, wherein the method comprises the following steps: the temperature of the ion chromatographic column is 30 ℃ in the using process, and the sample injection amount is 10 mu L during the detection of the ion chromatographic column.
5. The method for detecting trifluoroacetic acid in vildagliptin according to any of claims 1 to 4, wherein: and further comprises the step of adding water to the vildagliptin for dissolving and diluting, and then adding the vildagliptin into a protective column of the ion chromatographic column.
6. The method for detecting trifluoroacetic acid in vildagliptin according to claim 5, wherein: the detection limit of the trifluoroacetic acid in the method is 1ng/ml, and the quantification limit is 5ng/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010806723.6A CN112067733B (en) | 2020-08-12 | 2020-08-12 | Method for detecting trifluoroacetic acid in vildagliptin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010806723.6A CN112067733B (en) | 2020-08-12 | 2020-08-12 | Method for detecting trifluoroacetic acid in vildagliptin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112067733A CN112067733A (en) | 2020-12-11 |
| CN112067733B true CN112067733B (en) | 2022-12-30 |
Family
ID=73661288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010806723.6A Active CN112067733B (en) | 2020-08-12 | 2020-08-12 | Method for detecting trifluoroacetic acid in vildagliptin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112067733B (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108760946A (en) * | 2018-04-10 | 2018-11-06 | 开封康诺药业有限公司 | A kind of method of trifluoroacetic acid in detection Coenzyme I |
-
2020
- 2020-08-12 CN CN202010806723.6A patent/CN112067733B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN112067733A (en) | 2020-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110031573B (en) | Method for measuring vitamin D content by two-dimensional column switching high performance liquid chromatography | |
| CN114994212A (en) | High performance liquid chromatography detection method for hydroxylamine residue in medicine | |
| CN109580821B (en) | Method for detecting impurity succinic acid in S-benzylsuccinic acid | |
| CN108061767B (en) | Method for separating and measuring rivaroxaban intermediate and related impurities thereof by HP L C method | |
| CN112067733B (en) | Method for detecting trifluoroacetic acid in vildagliptin | |
| CN117092251A (en) | Detection method of taurine and sulfoalanine in cysteine raw material and application thereof | |
| CN110954629A (en) | Control method for measuring content of furfuryl amine in furosemide | |
| CN113325118B (en) | Method for measuring sodium content in parecoxib sodium | |
| CN111044640B (en) | Method for determining content of gamma-aminobutyric acid in feed additive by GC (gas chromatography) method | |
| CN112903836B (en) | Method for determining isopropyl-beta-D-thiogalactopyranoside in-vitro cultured bear gall powder | |
| CN113156025A (en) | Method for determining kanamycin in-vitro cultured bear gall powder | |
| CN112285248A (en) | Nitrite detection method | |
| CN115436522B (en) | Method for detecting impurity content of criatinib intermediate | |
| CN111337619B (en) | Method for analyzing ibandronate sodium drug by ion chromatography | |
| CN117288869B (en) | Method for detecting p-toluenesulfonate impurities in bulk drug | |
| CN114660196B (en) | Method for measuring related substances in medicine containing multi-component compound sorbitol solution | |
| CN116858978B (en) | Method for simultaneously detecting insulin aspart and insulin deglutition and plasma sample processing method thereof | |
| CN114755326B (en) | Detection method of difenoconazole in hydroxypropyl methylcellulose | |
| CN113866329B (en) | Method for detecting isocyanate potential genotoxic impurities in glimepiride tablets | |
| CN117554526A (en) | Method for determining S-1-amino-3-chloro-2-propanol hydrochloride and enantiomer thereof | |
| CN117783358A (en) | Method for separating and measuring critical starting materials and related impurities of ritatist by HPLC (high Performance liquid chromatography) | |
| CN117147734A (en) | Ion chromatography assay for anions and cations in urine sample | |
| CN117949552A (en) | Detection method of telmisartan related substances | |
| CN116718706A (en) | Method for detecting content of sodium bisulfite in dobutamine hydrochloride injection | |
| CN117269407A (en) | Method for detecting nitrite by adopting ion chromatography |
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 |