CN111189937A - Liquid phase detection and separation method for aspirin bulk drug related substances - Google Patents
Liquid phase detection and separation method for aspirin bulk drug related substances Download PDFInfo
- Publication number
- CN111189937A CN111189937A CN202010013222.2A CN202010013222A CN111189937A CN 111189937 A CN111189937 A CN 111189937A CN 202010013222 A CN202010013222 A CN 202010013222A CN 111189937 A CN111189937 A CN 111189937A
- Authority
- CN
- China
- Prior art keywords
- aspirin
- solution
- liquid phase
- taking
- raw material
- 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.)
- Granted
Links
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 41
- 238000001514 detection method Methods 0.000 title claims abstract description 24
- 238000000926 separation method Methods 0.000 title claims abstract description 17
- 239000007791 liquid phase Substances 0.000 title claims abstract description 15
- 229940088679 drug related substance Drugs 0.000 title claims abstract description 11
- 239000000243 solution Substances 0.000 claims abstract description 23
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000012535 impurity Substances 0.000 claims abstract description 20
- 239000012071 phase Substances 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 18
- 239000007788 liquid Substances 0.000 claims abstract description 16
- 238000010828 elution Methods 0.000 claims abstract description 14
- 239000012085 test solution Substances 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 11
- 229940079593 drug Drugs 0.000 claims abstract description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- FGDQGIKMWOAFIK-UHFFFAOYSA-N acetonitrile;phosphoric acid Chemical compound CC#N.OP(O)(O)=O FGDQGIKMWOAFIK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000945 filler Substances 0.000 claims abstract description 4
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 4
- 239000012488 sample solution Substances 0.000 claims description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- KIEFFPFIBREPIX-UHFFFAOYSA-N 2-(2,4-dihydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1O KIEFFPFIBREPIX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000010829 isocratic elution Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000000789 acetogenic effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/30—Control of physical parameters of the fluid carrier of temperature
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
- G01N2030/324—Control of physical parameters of the fluid carrier of pressure or speed speed, flow rate
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a liquid phase detection separation method of aspirin bulk drug related substances, which comprises the following steps: taking aspirin bulk drug, preparing a test solution, injecting the test solution into a high performance liquid chromatograph, and detecting and recording a chromatogram map under the following chromatographic conditions: octadecylsilane chemically bonded silica is used as a filling agent; taking 0.1% phosphoric acid water solution as a mobile phase A; taking a 0.1% acetonitrile phosphate solution as a mobile phase B; the elution mode is gradient elution; the flow rate is 0.95-1.05 ml/min; the detection wavelength is 235-239 nm; the column temperature is 23-27 ℃. According to the technical scheme, various impurities in the aspirin raw material medicine can be effectively separated by adopting the chromatographic conditions.
Description
Technical Field
The invention relates to the technical field of pharmaceutical analysis, in particular to a liquid phase detection separation method for related substances of aspirin bulk drug.
Background
Aspirin (Aspirin, acetylsalicylic acid) is a white crystal or crystalline powder, odorless or slightly acetogenic, slightly soluble in water, readily soluble in ethanol, soluble in ether and chloroform, and acidic in aqueous solution.
Aspirin bulk drug currently disclosed has 6 impurities, as shown in the following table:
wherein, the aspirin impurity A and the aspirin impurity B have larger polarity. In the high performance liquid chromatography determination method mentioned in pharmacopoeias of various countries at present, an isocratic elution mode is adopted for impurity separation, and in a chromatogram of isocratic elution, the peak shape of each impurity is poor, and the later-period quantification is inaccurate.
Disclosure of Invention
The invention mainly aims to provide a liquid phase detection separation method for related substances of aspirin bulk drug, and aims to solve the problems that the peak shape of each impurity in the detection of related substances of aspirin bulk drug is poor and the later-period quantification is inaccurate in the prior art.
In order to achieve the purpose, the invention provides a liquid phase detection separation method of aspirin bulk drug related substances, which comprises the following steps:
taking aspirin bulk drug, preparing a test solution, injecting the test solution into a high performance liquid chromatograph, and detecting and recording a chromatogram map under the following chromatographic conditions:
octadecylsilane chemically bonded silica is used as a filling agent;
taking 0.1% phosphoric acid water solution as a mobile phase A;
taking a 0.1% acetonitrile phosphate solution as a mobile phase B;
the elution mode is gradient elution;
the flow rate is 0.95-1.05 ml/min;
the detection wavelength is 235-239 nm;
the column temperature is 23-27 ℃.
Preferably, the flow rate is 1.0ml/min, the detection wavelength is 237nm, and the column temperature is 25 ℃.
Preferably, the gradient elution is in particular:
preferably, the test solution is a solution containing 10mg of aspirin raw drug substance per 1 ml.
Preferably, before the detection of the test solution, the method further comprises the following steps:
preparing a mixed solution containing 10mg of main component and 0.015mg of aspirin-related substance impurities A, B, C, D, E and F respectively in each 1ml of solution to serve as a system applicability solution;
and (3) injecting the system applicability solution into a high performance liquid chromatograph, and detecting and recording a chromatogram under the chromatographic condition.
The technical scheme of the invention is that octadecylsilane chemically bonded silica is used as a filling agent; the gradient elution is carried out by taking 0.1% phosphoric acid aqueous solution as a mobile phase A and taking 0.1% phosphoric acid acetonitrile solution as a mobile phase B, so that various impurities in the aspirin raw material medicine can be effectively separated.
Drawings
FIG. 1 is a liquid phase detection chromatogram of related substances of aspirin raw drug substance in example 1;
FIG. 2 is a liquid phase detection chromatogram of related substances of aspirin raw drug substance in example 2;
FIG. 3 is a liquid phase chromatogram for detection of related substances in aspirin bulk drug in example 3.
Detailed Description
The present invention will be described in further detail below by way of examples, but it should not be construed that the scope of the subject matter of the present invention is limited to the following examples. Such changes and modifications as would normally occur to one skilled in the art to which the invention relates are deemed to be within the scope and ambit of the invention as defined by the appended claims.
The invention provides a liquid phase detection and separation method of aspirin bulk drug related substances, which comprises the following steps:
preparing a mixed solution containing 10mg of a main component and 0.015mg of each of aspirin-related substance impurities A, B, C, D, E and F in each 1ml of the mixed solution as a system applicability solution, precisely measuring 10ul of the system applicability solution, injecting the system applicability solution into a liquid chromatograph, recording a chromatogram, and sequentially outputting a peak for the impurities A, B, aspirin, C, D, E and F in the system applicability, wherein the system applicability requires that: the separation degree between impurity peaks is more than 1.5, and the separation degree between the main component and the impurity C is more than 6.0.
Taking aspirin raw material medicine, preparing a solution containing 10mg of aspirin raw material medicine per 1ml as a test solution, and injecting the test solution into a high performance liquid chromatograph. The mobile phase comprises a mobile phase A and a mobile phase B, wherein the mobile phase A is a 0.1% phosphoric acid aqueous solution, and the mobile phase B is a 0.1% phosphoric acid acetonitrile solution. An ultraviolet detector is adopted, the detection wavelength can be 235-239 nm, the flow rate is 0.95-1.05 ml/min, the column temperature is 23-27 ℃, and elution is carried out according to the elution gradient shown in the table 1:
TABLE 1 gradiometer
Example 1
High performance liquid chromatograph: thermo U3000 (seemer fly);
a chromatographic column: phenomenex Gemini C8 column (150mm X4.6 mm, 5um)
Mobile phase A: adding 1.0ml phosphoric acid into 1000ml water and mixing uniformly to obtain the product
Mobile phase B: adding 1.0ml phosphoric acid into 1000ml acetonitrile and mixing evenly to obtain the product
The gradient elution procedure was performed with reference to the above table 1 gradient table:
the flow rate is 1.0 ml/min;
the detection wavelength is 237 nm;
the column temperature was 25 ℃.
The implementation steps are as follows: a solution containing 10mg of aspirin raw material medicine per 1ml is prepared to be used as a test solution.
Precisely measuring 10ul of the sample solution, injecting into a liquid chromatograph, and recording chromatogram, wherein the result is shown in Table 2 (the corresponding liquid chromatogram is shown in figure 1)
Table 2 example 1 liquid chromatography test results
| Impurities | Retention time | Degree of separation | Symmetry factor |
| A | 4.820 | 8.92 | 0.81 |
| B | 7.492 | 2.52 | 1.07 |
| C | 12.183 | 23.77 | 1.28 |
| D | 19.643 | 10.43 | 0.99 |
| E | 22.600 | 15.36 | 1.02 |
| F | 27.885 | n.a. | 1.02 |
| Aspirin | 8.295 | 11.65 | 0.86 |
Therefore, aspirin peaks can be effectively separated from adjacent impurity peaks and impurity peaks, and the separation degree is greater than 1.5.
Example 2
High performance liquid chromatograph: thermo U3000 (seemer fly);
a chromatographic column: phenomenex Gemini C8 column (150mm X4.6 mm, 5um)
Mobile phase A: adding 1.0ml phosphoric acid into 1000ml water and mixing uniformly to obtain the product
Mobile phase B: adding 1.0ml phosphoric acid into 1000ml acetonitrile and mixing evenly to obtain the product
The gradient elution procedure was performed with reference to the gradient table of table 1 above,
the flow rate is 1.0 ml/min;
the detection wavelength is 237 nm;
the column temperature was 25 ℃.
The implementation steps are as follows: a solution containing 10mg of aspirin raw material medicine per 1ml is prepared to be used as a test solution.
Precisely measuring 10ul of the sample solution, injecting into a liquid chromatograph, and recording chromatogram, wherein the result is shown in Table 3 (the corresponding liquid chromatogram is shown in figure 2)
Table 2 example 2 liquid chromatography test results
| Impurities | Retention time | Degree of separation | Symmetry factor |
| A | 7.195 | 13.59 | 0.87 |
| B | 12.200 | 7.57 | 1.00 |
| C | 19.538 | 31.90 | 1.25 |
| D | 28.493 | 11.20 | 1.06 |
| E | 30.993 | 15.10 | 1.07 |
| F | 34.735 | n.a. | 1.03 |
| Aspirin | 14.798 | 14.55 | 1.03 |
Therefore, aspirin peaks can be effectively separated from adjacent impurity peaks and impurity peaks, and the separation degree is greater than 1.5.
Example 3
High performance liquid chromatograph: thermo U3000 (seemer fly);
a chromatographic column: phenomenex Gemini C8 column (150mm X4.6 mm, 5um)
Mobile phase A: adding 1.0ml phosphoric acid into 1000ml water and mixing uniformly to obtain the product
Mobile phase B: adding 1.0ml phosphoric acid into 1000ml acetonitrile and mixing evenly to obtain the product
The gradient elution procedure was performed with reference to the gradient table of table 1 above,
the flow rate is 1.0 ml/min;
the detection wavelength is 237 nm;
the column temperature was 25 ℃.
The implementation steps are as follows: a solution containing 10mg of aspirin raw material medicine per 1ml is prepared to be used as a test solution.
Precisely measuring 10ul of the sample solution, injecting into a liquid chromatograph, and recording chromatogram, wherein the result is shown in Table 4 (the corresponding liquid chromatogram is shown in figure 3)
Table 3 example 3 liquid chromatography test results
Therefore, aspirin peaks can be effectively separated from adjacent impurity peaks and impurity peaks, and the separation degree is greater than 1.5.
The above description is only a part of or preferred embodiments of the present invention, and neither the text nor the drawings should be construed as limiting the scope of the present invention, and all equivalent structural changes, which are made by using the contents of the present specification and the drawings, or any other related technical fields, are included in the scope of the present invention.
Claims (5)
1. A liquid phase detection separation method for related substances of aspirin bulk drug is characterized by comprising the following steps:
taking aspirin bulk drug, preparing a test solution, injecting the test solution into a high performance liquid chromatograph, and detecting and recording a chromatogram map under the following chromatographic conditions:
octadecylsilane chemically bonded silica is used as a filling agent;
taking 0.1% phosphoric acid water solution as a mobile phase A;
taking a 0.1% acetonitrile phosphate solution as a mobile phase B;
the elution mode is gradient elution;
the flow rate is 0.95-1.05 ml/min;
the detection wavelength is 235-239 nm;
the column temperature is 23-27 ℃.
2. The method for detecting and separating the liquid phase of aspirin raw material drug related substance according to claim 1, characterized in that the flow rate is 1.0ml/min, the detection wavelength is 237nm, and the column temperature is 25 ℃.
3. The liquid phase detection and separation method of aspirin raw material drug-related substances according to claim 1, characterized in that the gradient elution specifically comprises:
4. the method for detecting and separating the liquid phase of aspirin raw material medicine-related substance according to claim 1, characterized in that the sample solution is a solution containing 10mg of aspirin raw material medicine per 1 ml.
5. The method for detecting and separating the liquid phase of aspirin raw material drug-related substance according to claim 1, characterized in that before the detection of the test solution, the method further comprises the following steps:
preparing a mixed solution containing 10mg of main component and 0.015mg of aspirin-related substance impurities A, B, C, D, E and F respectively in each 1ml of solution to serve as a system applicability solution;
and (3) injecting the system applicability solution into a high performance liquid chromatograph, and detecting and recording a chromatogram under the chromatographic condition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010013222.2A CN111189937B (en) | 2020-01-06 | 2020-01-06 | Liquid phase detection separation method for related substances of aspirin bulk drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010013222.2A CN111189937B (en) | 2020-01-06 | 2020-01-06 | Liquid phase detection separation method for related substances of aspirin bulk drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111189937A true CN111189937A (en) | 2020-05-22 |
| CN111189937B CN111189937B (en) | 2023-11-21 |
Family
ID=70708389
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010013222.2A Active CN111189937B (en) | 2020-01-06 | 2020-01-06 | Liquid phase detection separation method for related substances of aspirin bulk drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111189937B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113406242A (en) * | 2021-07-15 | 2021-09-17 | 江苏万珺医药科技有限公司 | Detection method of aspirin-related substances |
-
2020
- 2020-01-06 CN CN202010013222.2A patent/CN111189937B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| AHMED MAHDI SAEED ET AL.: "QUANTITATIVE ASSAY OF ASPIRIN AND (SALICYLIC ACID AND HEAVY METALS AS IMPURATIES) IN IRAQI’S MARKET ASPIRIN TABLETS USING DIFFERENT ANALYTICAL METHODS" * |
| SUBASRANJAN ACHARYA ET AL.: "Isolation, Characterization of a Potential Degradation Product of Aspirin and an HPLC Method for Quantitative Estimation of Its Impurities" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113406242A (en) * | 2021-07-15 | 2021-09-17 | 江苏万珺医药科技有限公司 | Detection method of aspirin-related substances |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111189937B (en) | 2023-11-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cazes | Encyclopedia of Chromatography 2004 Update Supplement | |
| Gomis et al. | Simultaneous determination of fat-soluble vitamins and provitamins in milk by microcolumn liquid chromatography | |
| Gambardella et al. | Quantitative determination and separation of analogues of aminoglycoside antiobiotcs by high-performance liquid chromatography | |
| CN106940355B (en) | A kind of brufen, the detection method of its sodium salt and its preparation in relation to substance | |
| CN111141850A (en) | Liquid phase detection and separation method for acetaminophen bulk drug related substances | |
| CN103323540B (en) | Content determination method for amino acids in Jinshuibao preparation | |
| CN104407077B (en) | The HPLC detection method that a kind of MES, NHS are residual | |
| CN105467021B (en) | A kind of method in relation to substance in HPLC method separation determination paricalcitol bulk pharmaceutical chemicals and preparation | |
| CN111189937A (en) | Liquid phase detection and separation method for aspirin bulk drug related substances | |
| CN103063789B (en) | The liquid phase analysis method of 12 amide alkaloids in detection great Ye simultaneously | |
| CN103076421B (en) | Analytic method for related substance examination of rebamipide | |
| CN105301159A (en) | High performance liquid chromatography analysis method of sirolimus | |
| CN111487354A (en) | Method for detecting cefixime related impurities | |
| Hashem et al. | Chromatographic applications on monolithic columns: determination of triamcinolone, prednisolone and dexamethasone in pharmaceutical tablet formulations using a solid phase extraction and a monolithic column | |
| CN107505409B (en) | A method of measuring isomer impurities ginsenoside RK1 in ginsenoside RZ1 raw materials or preparation | |
| CN106770849A (en) | A kind of detection method for determining doxercalciferol and its impurities | |
| CN107167535B (en) | Method for detecting raltitrexed enantiomer by reversed phase liquid chromatography | |
| CN111141851A (en) | Liquid phase detection and separation method for related substances of aspirin-containing compound preparation | |
| CN106483202B (en) | Method for separating and measuring alitretinoin and isomers | |
| CN108120772B (en) | Method for detecting genetic toxicity impurities in edaravone and sodium chloride injection thereof | |
| CN111141849A (en) | Liquid phase detection and separation method for positional isomer of dexmedetomidine starting material | |
| Gordon et al. | Determination of triamcinolone acetonide in cream and suspension formulations by high-performance liquid chromatography | |
| Lorenz et al. | Determination of process-related impurities and degradation products in cefaclor by high-performance liquid chromatography | |
| Krieger | Liquid chromatographic determination of acetaminophen in multicomponent analgesic tablets | |
| CN102375044B (en) | Method for analyzing related substance from hydrochloric acid bendamustine intermediate Z6 |
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 | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20230113 Address after: Floor 9, building F6, Jiangsu life science and Technology Innovation Park, No. 9, Weidi Road, Qixia District, Nanjing, Jiangsu 210033 Applicant after: SKYRUN PHARMA Co.,Ltd. Applicant after: BAIYUNSHAN HEJIGONG PHARMACEUTICAL FACTORY, GUANGZHOU BAIYUNSHAN PHARMACEUTICAL HOLDINGS Co.,Ltd. Address before: Floor 9, building F6, Jiangsu life science and Technology Innovation Park, No. 9, Weidi Road, Qixia District, Nanjing, Jiangsu 210033 Applicant before: SKYRUN PHARMA Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |