CN101968467A - Quality control method for edaravone and edaravone-containing preparation - Google Patents
Quality control method for edaravone and edaravone-containing preparation Download PDFInfo
- Publication number
- CN101968467A CN101968467A CN2010102800075A CN201010280007A CN101968467A CN 101968467 A CN101968467 A CN 101968467A CN 2010102800075 A CN2010102800075 A CN 2010102800075A CN 201010280007 A CN201010280007 A CN 201010280007A CN 101968467 A CN101968467 A CN 101968467A
- Authority
- CN
- China
- Prior art keywords
- edaravone
- high performance
- liquid chromatography
- performance liquid
- water
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a quality control method for edaravone and an edaravone-containing preparation. In the method, an impurity, namely, 2,2',4,4'-tetrahydrophthalic anhydride-5,5'-dimethyl-2,2'-diphenyl-[4,4'-di-3H-parazole]-3,3'-dione in the edaravone and an edaravone preparation is determined quantitatively by photoelectric technology. By the technical scheme of the invention, the qualities of the edaravone and an edaravone-containing medicament preparation can be evaluated and controlled more reliably and accurately.
Description
Technical field:
The present invention relates to the method for quality control of a kind of medicine and preparation thereof, be specifically related to a kind of cranial nerve protective agent Edaravone and contain the method for quality control of the preparation of Edaravone.
Background technology:
Edaravone (Edaravone) is a kind of in the pyrazolone derivative, its chemistry 3-methyl isophthalic acid-phenyl by name-2-pyrazoles woods-5-ketone, molecular formula C
10H
10N
2O, chemical structural formula is as follows:
Edaravone is that Mitsubishi Tokyo drugmaker at first develops, and ratified clinical use, trade name Radicut in Japan by medical workfare portion April 4 calendar year 2001.This medicine is a liquid drugs injection in Japan's listing formulation, specification is 30mg/20ml, auxiliary material is sodium bisulfite and cysteine hydrochloride, usually using dosage is each 30mg, every day 2 times, be dissolved in physiological saline or other dilution iv drip, general continuous use is no more than 14 days, is used to improve the various psychoneurosis shapes and the various dysfunction of acute period of cerebral infarction.
Owing to Edaravone is easy to generate impurity in synthetic and formulation preparation process, influence the bad reaction that drug activity also may increase medicine, brought difficulty for production and clinical use.Because the purity level that how much has reflected medicine of impurity content, and the purity of medicine is the leading indicator of drug quality quality, therefore the determination of foreign matter method in a kind of effective Edaravone and the preparation thereof has great importance to the quality of control Edaravone and the clinical efficacy of assurance Edaravone preparation.
Summary of the invention:
The present invention has overcome deficiency of the prior art, and a kind of Edaravone and the method for quality control that contains the pharmaceutical preparation of Edaravone are provided.
Technical scheme of the present invention is a kind of Edaravone and the method for quality control that contains the pharmaceutical preparation of Edaravone, adopt photoelectric technology to the impurity in Edaravone and the preparation thereof in this method: 2,2 ', 4,4 '-tetrahydrochysene-5,5 '-dimethyl-2,2 '-diphenyl-[4,4 '-two-3H-pyrazoles]-3,3 '-diketone (hereinafter to be referred as the Edaravone dimer, chemical structural formula is as follows) has carried out quantitative measurement.
2,2 ', 4,4 '-tetrahydrochysene-5,5 '-dimethyl-2,2 '-diphenyl-[4,4 '-two-3H-pyrazoles]-3,3 '-diketone
The types of drug preparations that wherein contains Edaravone comprises the suitable pharmaceutical dosage form of acceptable on the physiology, comprises liquid drugs injection, powder-injection, infusion solutions, tablet, capsule, granule, oral liquid, nasal drop, ointment, gel etc.
The dimeric method for quantitatively determining of impurity Edaravone can be selected following analysis means among the present invention: a. high performance liquid chromatography; B. high performance thin layer chromatography scanning method.
High performance liquid chromatography wherein, adopting octadecylsilane chemically bonded silica or eight alkyl silane bonded silica gels is the chromatographic column of filling agent, with the mixed solvent of organic phase and water as moving phase.Wherein the ratio of organic phase and water is 20～60: 80～40, and preferred proportion is 30～50: 70～30.
Organic phase wherein can be methyl alcohol or acetonitrile.Water wherein can be acetate buffer or phosphate buffer, and the pH scope is 3～8, and preferred pH scope is 3.5～5.5 phosphate buffer.
When using technical scheme of the present invention, can also can carry out pre-treatment to not doing extra processing for test agent to the preparation that contains Edaravone.Thereby the purpose of pre-treatment be make measurement result more clear and definite make things convenient for the professional to judge and read the result.The method of pre-treatment can be organic solvent extraction or Solid-Phase Extraction edulcoration purification.
Compared with prior art, advantage of the present invention provided a kind of more reliable, estimate Edaravone and contain the control method of the pharmaceutical preparation quality of Edaravone more accurately, use technical scheme of the present invention can carry out accurate impurity quantitative measurement to the pharmaceutical preparation that contains Edaravone.
Embodiment
Below in conjunction with embodiment the present invention is described in further detail:
Embodiment 1: the dimeric content of impurity Edaravone in the high effective liquid chromatography for measuring Edaravone
Measure according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia).
Chromatographic condition and system suitability test are filling agent with octadecylsilane chemically bonded silica, (contain 0.1mol/LNaH with water
2PO
4, H
3PO
4Transfer pH to 4.0)-methyl alcohol (60: 40) is moving phase, the detection wavelength is 243nm.
It is an amount of that the Edaravone sample is got in the preparation of need testing solution, adds moving phase and make the solution that contains 0.5mg among every 1ml, as need testing solution.
The preparation of Edaravone dimer reference substance solution gets 2,2 ', 4,4 '-tetrahydrochysene-5,5 '-dimethyl-2,2 '-diphenyl-[4,4 '-two-3H-pyrazoles]-3,3 '-diketone reference substance is an amount of, and accurate the title, decide, add moving phase and make the solution that every 1ml contains 2.0 μ g, as Edaravone dimer reference substance solution.
Precision is measured need testing solution to determination method respectively, each 20 μ L of reference substance solution inject liquid chromatograph, presses external standard method with calculated by peak area, promptly.
Claims (8)
1. an Edaravone and contain the method for quality control of the preparation of Edaravone, it is characterized in that in this method adopting photoelectric technology to the impurity in Edaravone and the preparation thereof: 2,2 ', 4,4 '-tetrahydrochysene-5,5 '-dimethyl-2,2 '-diphenyl-[4,4 '-two-3H-pyrazoles]-3,3 '-diketone carries out quantitative measurement.
2. method according to claim 1 is characterized in that impurity: 2,2 ', 4,4 '-tetrahydrochysene-5,5 '-dimethyl-2,2 '-diphenyl-[4,4 '-two-3H-pyrazoles]-3, the method for quantitatively determining of 3 '-diketone can be selected following analysis means: a. high performance liquid chromatography; B. high performance thin layer chromatography scanning method.
3. high performance liquid chromatography according to claim 2, it is characterized in that adopting octadecylsilane chemically bonded silica or eight alkyl silane bonded silica gels is the chromatographic column of filling agent, with the mixed solvent of organic phase and water as moving phase.
4. high performance liquid chromatography according to claim 3 is characterized in that wherein the ratio of organic phase and water is 20～60: 80～40.
5. high performance liquid chromatography according to claim 3 is characterized in that wherein the ratio of organic phase and water is 30～50: 70～30.
6. high performance liquid chromatography according to claim 3 is characterized in that organic phase wherein can be methyl alcohol or acetonitrile.
7. high performance liquid chromatography according to claim 3 is characterized in that water wherein can be acetate buffer or phosphate buffer, and the pH scope is 3～8.
8. high performance liquid chromatography according to claim 3 is characterized in that water wherein can be that the pH scope is 3.5～5.5 phosphate buffer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102800075A CN101968467A (en) | 2010-09-14 | 2010-09-14 | Quality control method for edaravone and edaravone-containing preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102800075A CN101968467A (en) | 2010-09-14 | 2010-09-14 | Quality control method for edaravone and edaravone-containing preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101968467A true CN101968467A (en) | 2011-02-09 |
Family
ID=43547652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102800075A Pending CN101968467A (en) | 2010-09-14 | 2010-09-14 | Quality control method for edaravone and edaravone-containing preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101968467A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098512A (en) * | 2013-04-03 | 2014-10-15 | 江苏先声药物研究有限公司 | Edaravone derivative, and preparation method, detection method and application thereof |
| CN105878171A (en) * | 2014-12-22 | 2016-08-24 | 南京海恒医药科技有限公司 | Novel edaravone preparation and preparation method thereof |
| CN106167465A (en) * | 2016-07-06 | 2016-11-30 | 扬子江药业集团江苏海慈生物药业有限公司 | A kind of Edaravone dimer impurity compound and preparation method thereof |
| CN108072710A (en) * | 2016-11-14 | 2018-05-25 | 江苏正大丰海制药有限公司 | A kind of Edaravone Sodium Chloride Injections Related Substances detection method |
| CN108203410A (en) * | 2016-12-20 | 2018-06-26 | 江苏先声药业有限公司 | The synthesis and application of a kind of impurity phenylhydrazine |
| CN113125608A (en) * | 2021-04-21 | 2021-07-16 | 扬子江药业集团上海海尼药业有限公司 | Impurity detection method of edaravone sodium chloride injection |
-
2010
- 2010-09-14 CN CN2010102800075A patent/CN101968467A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098512A (en) * | 2013-04-03 | 2014-10-15 | 江苏先声药物研究有限公司 | Edaravone derivative, and preparation method, detection method and application thereof |
| CN105878171A (en) * | 2014-12-22 | 2016-08-24 | 南京海恒医药科技有限公司 | Novel edaravone preparation and preparation method thereof |
| CN106167465A (en) * | 2016-07-06 | 2016-11-30 | 扬子江药业集团江苏海慈生物药业有限公司 | A kind of Edaravone dimer impurity compound and preparation method thereof |
| CN106167465B (en) * | 2016-07-06 | 2018-06-22 | 扬子江药业集团江苏海慈生物药业有限公司 | A kind of Edaravone dimer impurity compound and preparation method thereof |
| CN108072710A (en) * | 2016-11-14 | 2018-05-25 | 江苏正大丰海制药有限公司 | A kind of Edaravone Sodium Chloride Injections Related Substances detection method |
| CN108203410A (en) * | 2016-12-20 | 2018-06-26 | 江苏先声药业有限公司 | The synthesis and application of a kind of impurity phenylhydrazine |
| CN108203410B (en) * | 2016-12-20 | 2022-03-18 | 江苏先声药业有限公司 | Synthesis and application of edaravone impurity |
| CN113125608A (en) * | 2021-04-21 | 2021-07-16 | 扬子江药业集团上海海尼药业有限公司 | Impurity detection method of edaravone sodium chloride injection |
| CN113125608B (en) * | 2021-04-21 | 2023-08-29 | 扬子江药业集团上海海尼药业有限公司 | Impurity detection method for edaravone sodium chloride injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wankhede et al. | RP-HPLC Method for Simultaneous Estimation of Telmisartan and Hydrochlorothiazide in Tablet Dosage Form. | |
| CN101968467A (en) | Quality control method for edaravone and edaravone-containing preparation | |
| CN103344733B (en) | High performance liquid chromatographic separation detection method for bortezomib enantiomers | |
| CN104965041B (en) | A kind of high-efficiency liquid chromatography method for detecting of Parecoxib Sodium isomer | |
| CN108226309A (en) | A kind of analysis method of dexrazoxane | |
| CN108828127A (en) | Liquid-phase chromatography method in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate | |
| CN104931599A (en) | Determining method of atorvastatin calcium related substance | |
| CN102138892B (en) | Choline alfoscerate injection preparation as well as preparation method and detection method thereof | |
| CN105424822A (en) | Method for detecting (1R,2S)-2-(3,4-diflurophenyl) cyclopropylamine in ticagrelor | |
| CN105510482A (en) | Method for detecting content of isomer impurity in raw material for ticagrelor | |
| CN102375033A (en) | High performance liquid chromatographic analysis method of bendamustine hydrochloride and its related substances | |
| CN105806966A (en) | Quality control method for high optical purity folic acid preparation process | |
| CN110441424A (en) | Method in relation to substance in a kind of liquid chromatography analysis measurement pyrazinamide | |
| CN104297357A (en) | Method for determining content of mythyl p-hydroxybenzoate and sodium benzoate in solution | |
| CN103926335B (en) | The high-efficient liquid phase chromatogram process measuring method of related substance in a kind of Dapoxetine hydrochloride | |
| CN102636600B (en) | Method for determination of optical isomers in palonosetron hydrochloride composition | |
| CN1790013B (en) | Method for simultaneous determination of protocatechuic acid content and 5-hydroxymethyl furfural content in pulse-activating injection | |
| CN103675184B (en) | The method of quality control of a kind of Pazufloxacin Mesilate and ejection preparation | |
| Patel et al. | Simultaneous estimation of pantoprazole and domperidone in pure powder and a pharmaceutical formulation by high-perfomance liquid chromatography and high-performance thin-layer chromatography methods | |
| CN104515816A (en) | Detection method of substances relative to raw material and preparation of ambrisentan | |
| CN103163228A (en) | Efficient liquid phase analysis method for hydroxyfasudil and preparation thereof | |
| CN110507605A (en) | A kind of stable ornidazole injection and S- ornidazole injection and preparation method thereof | |
| CN102579961B (en) | Detection method for aristolochic acid A in swelling-reducing and pain-alleviating tincture | |
| CN109521117A (en) | A kind of detection method of the ibuprofen injection in relation to substance | |
| CN104965031B (en) | Content measuring method for compound ketoprofen and omeprazole sustained-release capsules |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110209 |