CN111678999B - Method for detecting arbidol hydrochloride related substances - Google Patents

Method for detecting arbidol hydrochloride related substances Download PDF

Info

Publication number
CN111678999B
CN111678999B CN202010470426.9A CN202010470426A CN111678999B CN 111678999 B CN111678999 B CN 111678999B CN 202010470426 A CN202010470426 A CN 202010470426A CN 111678999 B CN111678999 B CN 111678999B
Authority
CN
China
Prior art keywords
solution
acetonitrile
arbidol hydrochloride
mobile phase
detecting
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
Application number
CN202010470426.9A
Other languages
Chinese (zh)
Other versions
CN111678999A (en
Inventor
孙立杰
张伟丽
延春霞
马永青
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shijiazhuang No 4 Pharmaceutical Co Ltd
Hebei Guolong Pharmaceutical Co Ltd
Original Assignee
Shijiazhuang No 4 Pharmaceutical Co Ltd
Hebei Guolong Pharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shijiazhuang No 4 Pharmaceutical Co Ltd, Hebei Guolong Pharmaceutical Co Ltd filed Critical Shijiazhuang No 4 Pharmaceutical Co Ltd
Priority to CN202010470426.9A priority Critical patent/CN111678999B/en
Publication of CN111678999A publication Critical patent/CN111678999A/en
Application granted granted Critical
Publication of CN111678999B publication Critical patent/CN111678999B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • 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
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G01N2030/065—Preparation using different phases to separate parts of sample

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 provides a related substance detection method capable of effectively controlling the quality of arbidol hydrochloride, which comprises the following steps: (1) preparing a test solution; (2) preparing a reference substance solution; (3) and (5) HPLC detection. The invention adopts a mobile phase gradient elution method, overcomes the problem that all key impurities and active ingredients cannot be completely separated in the prior art, further improves the quality of the arbidol hydrochloride by the quality control method, improves the existing industrial standard, has the advantages of simplicity, easy implementation and high precision and accuracy, and has great significance for improving the product quality.

Description

Method for detecting arbidol hydrochloride related substances
Technical Field
The invention belongs to the technical field of medicine invention, and particularly relates to a method for detecting substances related to arbidol hydrochloride.
Background
Abidol Hydrochloride (Arbidol Hydrochloride) is a non-nucleoside broad-spectrum antiviral drug with immune enhancement effect, and is used for treating upper respiratory tract infection caused by influenza A virus and influenza B virus. Arbidol is a non-nucleoside antiviral drug developed by the former soviet union chemical research center, first marketed in russia in 1993, where it has been used for many years to treat influenza. Currently, the therapeutic effect of arbidol is recognized and favored by international experts and is marketed in some countries in japan and europe, with a permission to market in china in 2006.
In recent years, research proves that the Abidol has certain inhibitory activity on SARS-CoV and MERS-CoV coronaviruses, and in addition, the research shows that the Abidol can effectively inhibit the coronaviruses by 60 times and obviously inhibit the pathological change effect of the viruses on cells under the condition that the Abidol is 10-30 micromolar compared with a control group which is not treated by medicaments. Based on the above research results, arbidol was included in "new coronavirus pneumonia diagnosis and treatment plan (trial sixth edition) formulated and issued by the national health and care committee of health care and agency, and the national administration of traditional Chinese medicine.
Abidol hydrochloride is not loaded in USP43-N38, EP9.8, BP2020, JP17 and Chinese pharmacopoeia 2015 edition, but is loaded in the second supplement book of Chinese pharmacopoeia 2010 edition. The key related substances of the arbidol hydrochloride bulk drug (API) reported at present comprise:
Figure BDA0002514087780000011
Figure BDA0002514087780000021
the second supplementary book of the Chinese pharmacopoeia 2010 edition adopts a chromatographic system: octadecylsilane chemically bonded silica is used as a filling agent, a mobile phase is a sodium heptanesulfonate solution (1.1 g of sodium heptanesulfonate and 5.9g of ammonium perchlorate are taken, a proper amount of water is added for dissolution, 13.2ml of triethylamine is added, the mixture is uniformly mixed, the water is used for diluting the mixture to 1000ml, the pH value is adjusted to 3.0 by phosphoric acid) -methanol (30: 70), the detection wavelength is 255nm, the flow rate is 1ml/min, each known impurity in the arbidol hydrochloride is investigated, and the impurity D is superposed with API, so that the control of the quality of the arbidol hydrochloride is influenced.
Patent CN102091048A adopts HPLC method to determine the content of related substances in the Arbidol tablet, but does not solve the problem that part of impurity D is overlapped with API.
In view of the defects of the prior art, technical personnel are urgently needed to develop a method for effectively controlling and detecting the quality of the arbidol hydrochloride so as to improve the industrial standard.
Disclosure of Invention
The invention aims to provide a method for detecting related substances of arbidol hydrochloride, which aims to overcome the defects that part of impurities and raw material medicines cannot be separated in the prior art, provide effective quality control of arbidol and improve the industrial standard.
The method for detecting the arbidol hydrochloride related substances comprises the following steps:
(1) preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the reference solution into a high performance liquid chromatograph,
wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.01-0.2 mol/L ammonium acetate solution-acetic acid (32: 4-36: 0), and the mobile phase B is acetonitrile; the flow rate is 1ml/min +/-0.4 ml/min, the column temperature is 30 +/-10 ℃, and the detection wavelength is 315nm +/-10 nm. The elution gradient was:
time min A％ B％
0 52 48
13 52 48
18 25 75
30 25 75
31 52 48
36 52 48
The mobile phase A is preferably 0.1mol/L ammonium acetate solution, preferably ammonium acetate solution: acetic acid 35: 1.
The mobile phase flow rate is preferably 1 ml/min.
The column temperature is preferably 30 ℃.
The detection wavelength is preferably 315 nm.
The gradient proportion of the mobile phase gradient at each time point varied within a range of ± 10%.
The prior art of quality control of arbidol hydrochloride is isocratic elution, has poor elution capability on impurities with small polarity, and has the risks of impurity omission and potential safety hazard due to the coincidence of the impurities and API. The invention greatly improves the separation degree among impurities in the Abidol and between the impurities and the API by adopting gradient elution so as to ensure that the separation degree meets the requirement. The detection wavelength in the invention can avoid the fluctuation of a base line in the detection, ensure the effective detection of impurities with small polarity and ensure the safety of the product.
Compared with the prior art, the invention has the following advantages:
1) gradient elution is adopted, so that the separation degree of key impurities of the arbidol hydrochloride is improved, and the product quality is more effectively controlled;
2) the detection wavelength of the invention can avoid the fluctuation of a base line in the detection, ensure the effective detection of impurities with small polarity and ensure the safety of the product.
3) The industrial standard is improved.
Drawings
FIG. 1 example 1 high performance liquid chromatogram
FIG. 2 high performance liquid chromatogram of comparative example 1
Detailed Description
The following examples are intended to illustrate the invention in detail, but are not intended to limit the invention.
Example 1
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.1mol/L ammonium acetate solution-acetic acid 35:1, and the mobile phase B is acetonitrile; the flow rate was 1ml/min, the column temperature was 30 ℃ and the detection wavelength was 315 nm. The elution gradient was:
time min A％ B％
0 52 48
13 52 48
18 25 75
30 25 75
31 52 48
36 52 48
Example 2
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.1mol/L ammonium acetate solution-acetic acid 35:1, and the mobile phase B is acetonitrile; the flow rate was 1ml/min, the column temperature was 20 ℃ and the detection wavelength was 315 nm. The elution gradient was:
time min A％ B％
0 52 48
13 52 48
18 25 75
30 25 75
31 52 48
36 52 48
Example 3
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: adding acetonitrile into a proper amount of a precise test sample solution, and quantitatively diluting to prepare a solution containing about 3 mu g of acetonitrile in each 1ml of the test sample solution as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.1mol/L ammonium acetate solution-acetic acid 35:1, and the mobile phase B is acetonitrile; the flow rate was 1ml/min, the column temperature was 40 ℃ and the detection wavelength was 315 nm. The elution gradient was:
time min A％ B％
0 52 48
13 52 48
18 25 75
30 25 75
31 52 48
36 52 48
Example 4
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.1mol/L ammonium acetate solution-acetic acid 35:1, and the mobile phase B is acetonitrile; the flow rate was 0.6ml/min, the column temperature was 30 ℃ and the detection wavelength was 315 nm. The elution gradient was:
time min A％ B％
0 52 48
13 52 48
18 25 75
30 25 75
31 52 48
36 52 48
Example 5
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.1mol/L ammonium acetate solution-acetic acid 35:1, and the mobile phase B is acetonitrile; the flow rate was 1.4ml/min, the column temperature was 30 ℃ and the detection wavelength was 315 nm. The elution gradient was:
Figure BDA0002514087780000061
Figure BDA0002514087780000071
example 6
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.01mol/L ammonium acetate solution, and the mobile phase B is acetonitrile; the flow rate was 1.0ml/min, the column temperature was 30 ℃ and the detection wavelength was 305 nm. The elution gradient was:
time min A％ B％
0 42 58
13 42 58
18 15 85
30 15 85
31 42 58
36 42 58
Example 7
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution; (3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as filler (CAPCELL MG II 4.6mm × 250mm, 5 μm or equivalent chromatographic column); the mobile phase A is 0.2mol/L ammonium acetate solution-acetic acid 32:4, and the mobile phase B is acetonitrile; the flow rate was 1.0ml/min, the column temperature was 30 ℃ and the detection wavelength was 325 nm. The elution gradient was:
time min A％ B％
0 62 38
13 62 38
18 35 65
30 35 65
31 62 38
36 62 38
Comparative example 1
(1) Preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the control solution into a high performance liquid chromatograph, wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as a filler for a chromatographic column; mobile phase: sodium heptanesulfonate solution (1.1 g sodium heptanesulfonate and 5.9g ammonium perchlorate are taken and dissolved by adding a proper amount of water, 13.2ml triethylamine is added, the mixture is mixed evenly and diluted to 1000ml by water, and the pH value is adjusted to 3.0 by phosphoric acid) -methanol (30: 70); the flow rate is 1 ml/min; the column temperature is 30 ℃; the detection wavelength was 255 nm.
And (3) test results:
examples 1-3 examine the influence of different column temperatures on the separation degree of impurity D and API, and the results show that: the column temperature varies within the range of 20 ℃ to 40 ℃, and the degree of separation of the impurity D from the API meets the specification.
Examples 1, 4, 5 examining the effect of different flow rates on the degree of separation of impurity D from the API, the results show that: the flow rate is changed within the range of 0.6ml/min to 1.4ml/min, and the separation degree of the impurity D and the API accords with the regulation.
By adopting the detection method, the separation degree of the impurity D and the API meets the requirement, and the separation degree of other impurities is obviously superior to that of the second supplement (comparative example 1) method in 2010 edition of Chinese pharmacopoeia. The quality of the arbidol hydrochloride can be better controlled by selecting the detection method provided by the invention.

Claims (5)

1. A method for detecting related substances of arbidol hydrochloride is characterized by comprising the following steps:
(1) preparing a test solution: taking a proper amount of arbidol hydrochloride, precisely weighing, dissolving with acetonitrile, and quantitatively diluting to prepare a solution containing 0.3mg in each 1 ml;
(2) preparation of control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting with acetonitrile to obtain a solution containing about 3 mug of acetonitrile in each 1ml as a control solution;
(3) and (3) detection: respectively injecting the test solution and the reference solution into a high performance liquid chromatograph,
wherein the chromatographic conditions are as follows:
octadecylsilane chemically bonded silica is used as a filling agent; the mobile phase A is 0.01-0.2 mol/L ammonium acetate solution-acetic acid with the volume ratio of 32: 4-36: 0, and the mobile phase B is acetonitrile; the flow rate is 1ml/min +/-0.4 ml/min, the column temperature is 30 ℃ +/-10 ℃, and the detection wavelength is 315nm +/-10 nm; the elution gradient was:
time min A％ B％ 0 52 48 13 52 48 18 25 75 30 25 75 31 52 48 36 52 48
The related substances are:
Figure FDA0003054960080000011
Figure FDA0003054960080000012
2. the method for detecting the substances related to the arbidol hydrochloride according to claim 1, wherein the mobile phase A is 0.1mol/L ammonium acetate solution-acetic acid with the volume ratio of 35: 1.
3. The method for detecting substances related to arbidol hydrochloride according to claim 1, wherein the flow rate of the mobile phase is 1 ml/min.
4. The method for detecting substances related to arbidol hydrochloride according to claim 1, wherein the column temperature is 30 ℃.
5. The method for detecting arbidol hydrochloride-related substances according to claim 1, wherein the detection wavelength is 315 nm.
CN202010470426.9A 2020-05-28 2020-05-28 Method for detecting arbidol hydrochloride related substances Active CN111678999B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010470426.9A CN111678999B (en) 2020-05-28 2020-05-28 Method for detecting arbidol hydrochloride related substances

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010470426.9A CN111678999B (en) 2020-05-28 2020-05-28 Method for detecting arbidol hydrochloride related substances

Publications (2)

Publication Number Publication Date
CN111678999A CN111678999A (en) 2020-09-18
CN111678999B true CN111678999B (en) 2021-07-02

Family

ID=72453473

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010470426.9A Active CN111678999B (en) 2020-05-28 2020-05-28 Method for detecting arbidol hydrochloride related substances

Country Status (1)

Country Link
CN (1) CN111678999B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114397375B (en) * 2021-12-09 2022-12-13 石家庄四药有限公司 Method for detecting related substances of arbidol hydrochloride intermediate
CN116466011B (en) * 2023-06-20 2023-09-12 则正(上海)生物科技有限公司 Detection method of arbidol hydrochloride related substances and application thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9452227B2 (en) * 2008-11-25 2016-09-27 Alderbio Holdings Llc Methods of treating or diagnosing conditions associated with elevated IL-6 using anti-IL-6 antibodies or fragments
CN102091048A (en) * 2009-12-09 2011-06-15 汪昌瑞 Preparation method and quality control method of arbidol hydrochloride tablet
CN102836134A (en) * 2012-08-31 2012-12-26 石家庄中硕药业集团有限公司 Method for preparing mesylate arbidol freeze-dried powder injection preparation
CN104698106B (en) * 2015-03-21 2016-06-29 石家庄四药有限公司 A kind of chemicals acotiamide hydrochloride hydrate has the detection method of related substance
CN105030710B (en) * 2015-09-08 2021-07-30 湖北生物医药产业技术研究院有限公司 Arbidol tablet
TR201907085A2 (en) * 2019-05-10 2020-11-23 Univ Yeditepe THE USE OF PARASITES AND EXTRACELULAR VESICULES OBTAINED FROM PARASITES IN CANCER TREATMENT
CN110412158B (en) * 2019-07-18 2022-08-30 浙江公正检验中心有限公司 Detection method for antiviral drug residues in animal-derived products

Also Published As

Publication number Publication date
CN111678999A (en) 2020-09-18

Similar Documents

Publication Publication Date Title
CN111678999B (en) Method for detecting arbidol hydrochloride related substances
JP7143972B2 (en) Ephedrine alkaloid-removed mahuang extract and its preparation and use
CN110261531B (en) Method for detecting related substances in loxoprofen or sodium salt thereof
CN110927279B (en) Method for separating imidapril hydrochloride related substances
CN106474048A (en) A kind of more stable desonide gel preparation of quality
CN108553433A (en) A kind of Azilsartan piece and preparation method thereof
CN109655544B (en) Quality control method of metformin hydrochloride and preparation thereof
CN108030924A (en) A kind of preparation method of high stability Aprepitant composition
Kalinin et al. Beta-amyloid-dependent expression of NOS2in neurons: prevention by an α2-adrenergic antagonist
CN114814060B (en) Detection method of valsartan amlodipine tablet related substances
CN110693861A (en) Terbutaline sulfate solution preparation for aerosol inhalation and preparation method thereof
CN108120772A (en) Genetoxic method for detecting impurities in a kind of Edaravone and its sodium chloride injection
CN113116935B (en) Bufonis venenum total lactone extract and preparation method and application thereof
CN103860461A (en) Medicinal composition containing active component ambroxol hydrochloride
CN106353428B (en) Quality standard of paracetamol and tramadol capsule
CN110907583A (en) Method for separating related substances in loxoprofen or sodium salt thereof
WO2021202320A1 (en) Methods for treating inflammatory and fibrotic diseases and disorders
RU2653191C1 (en) Method of acetate hydrocortizone, acetate cortisone, methylparagyroxibenzoate, propylparaghyroxibenzoate chromatographic separation by reverse phase high performance liquid chromatography
CN117347533B (en) Method for detecting related substances of compound paracetamol and renin tablets for children
CN115887406B (en) Preparation method of crizotinib capsule
CN115372528B (en) Detection method for simultaneously measuring various impurities in nitrofurantoin
CN111529485B (en) Preparation method of levetiracetam concentrated solution for injection
CN114948905A (en) Microsphere containing capecitabine and application thereof in liver cancer
CN117074594A (en) Quality control method of Ai Nuowei forest related substances
CN117849225A (en) Detection method of oxytocin related substances

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
CP02 Change in the address of a patent holder
CP02 Change in the address of a patent holder

Address after: 050035 No. 518, Huai'an East Road, high tech Industrial Development Zone, Shijiazhuang City, Hebei Province

Patentee after: SHIJIAZHUANG NO.4 PHARMACEUTICAL Co.,Ltd.

Patentee after: Hebei Guolong Pharmaceutical Co., Ltd

Address before: 050035 No. 288 Pearl River Avenue, Shijiazhuang Hi-tech Industrial Development Zone, Hebei Province

Patentee before: SHIJIAZHUANG NO.4 PHARMACEUTICAL Co.,Ltd.

Patentee before: Hebei Guolong Pharmaceutical Co., Ltd