Edaravone derivative, and preparation method, detection method and application thereof

A compound and aqueous solution technology, applied in the field of edaravone derivatives, achieves the effects of simple preparation method, high product purity and simple detection method

Inactive Publication Date: 2014-10-15
NANJING SIMCERE DONGYUAN PHARM CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

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Method used

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  • Edaravone derivative, and preparation method, detection method and application thereof
  • Edaravone derivative, and preparation method, detection method and application thereof
  • Edaravone derivative, and preparation method, detection method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: the preparation of compound A

[0029] Take 10g of Edaravone raw material drug and add methanol 200ml to dissolve, slowly add 50ml of hydrogen peroxide with a mass fraction of 30%, stir at room temperature 20°C for 48 hours, spin off part of the solvent at 10°C, and prepare the solution for later use.

[0030] Then adopt reverse-phase high performance liquid chromatography to separate above-mentioned solution, chromatographic condition is: chromatographic column is Waters Nova-Pak C18, 6 μ m, 190*300mm, mobile phase a is methyl alcohol: water: glacial acetic acid=45:55:0.1 , mobile phase b is methanol, flow rate: 20ml / min, column temperature: 20°C, detection wavelength: 244nm, injection volume: 0.5ml. Gradient elution is as follows:

[0031] time (min)

Proportion of mobile phase a (%)

Proportion of mobile phase b (%)

0

100

0

22

100

0

52

36

64

72

36

64

80

100

0

...

Embodiment 2

[0044] Embodiment 2: the preparation of compound A

[0045] Take 10g of Edaravone raw material drug and add 200ml of acetonitrile to dissolve, slowly add 50ml of hydrogen peroxide with a mass fraction of 30%, stir at room temperature 20°C for 48 hours, spin off part of the solvent at 10°C, and prepare the solution for later use.

[0046] Then adopt reverse-phase high performance liquid chromatography to separate above-mentioned solution, chromatographic condition is: chromatographic column is Waters Nova-Pak C18, 6 μ m, 190*300mm, mobile phase a is water: glacial acetic acid=99.9:0.1, mobile phase b Acetonitrile, flow rate: 20ml / min, column temperature: 20°C, detection wavelength: 244nm, injection volume: 0.5ml. Gradient elution is as follows:

[0047] time (min)

[0048] The preparation solution with a relative retention time of 2.3-2.9 was collected, and the solvent was spin-dried at 10°C to obtain 5 mg of compound A with a yield of 0.07%.

Embodiment 3

[0049] Embodiment 3: the detection of compound A

[0050] Preparation of sample: Accurately weigh 10 mg of Edaravone crude drug, place it in a 50ml volumetric flask, dissolve and settle to volume with methanol: water: glacial acetic acid=45:55:0.1 mixed solution, configure Edaravone content The sample is 0.2mg / ml, the temperature is controlled at 4°C, and it is prepared and prepared within half an hour.

[0051] Chromatographic conditions and detection:

[0052] Instrument: Agilent1200HPLC

[0053] Chromatographic column: Agilent Eclipse XDB-C18, 4.6*150mm (3.5μm);

[0054]Mobile phase a is methanol:water:glacial acetic acid=45:55:0.1, mobile phase b is methanol, flow rate: 0.8ml / min, column temperature: 20°C, detection wavelength: 244nm, injection volume: 20ml. Gradient elution is as follows:

[0055] time (min)

[0056] Test results: The peak eluting time of compound A was 17.3 min, and the peak eluting time of raw material phenylhydrazine was 1.8 min. (attach...

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Abstract

The invention discloses an edaravone derivative, and a preparation method, a detection method and application thereof. The invention relates to a compound with the structure shown in the specification, and a preparation method, a detection method and application thereof. The preparation method for the edaravone derivative is characterized by comprising: dissolving edaravone in an organic solvent, reacting with an aqueous solution of Hydrogen peroxide, then utilizing reversed-phase high-performance liquid chromatography to perform separation on the above edaravone reaction solution, so as to prepare (Z)-2-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyridin-4-yl)-3-[(E)-phenylazo]-2-butenoic acid. Additionally, the invention also provides the detection method for the compound. The compound can be used as a control sample of edaravone impurities, and is convenient for controlling edaravone bulk drugs and the content of the compound in correlated preparations.

Description

field of invention [0001] The present invention relates to an Edaravone derivative, namely (Z)-2-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl) -3-[(E)-phenylazo]-2-butenoic acid, its preparation method, detection method and use. Background technique [0002] Edaravone (compound of formula I) is a neuroprotective agent. The administration of edaravone to patients in the acute stage of cerebral infarction can inhibit the reduction of local cerebral blood flow around the infarction, and make the NAA content in the brain significantly higher than that of the glycerol control group on the 28th day after the onset. Edaravone can scavenge free radicals and inhibit lipid peroxidation, thereby inhibiting the oxidative damage of brain cells, vascular endothelial cells, and nerve cells. [0003] [0004] As a commonly used clinical drug, Edaravone may produce impurities during its production, storage, and use due to high-temperature processes such as sterilization, resulti...

Claims

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Application Information

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IPC IPC(8): C07D231/26G01N30/02
CPCC07D231/26G01N30/02
Inventor 刘雯雯廖明毅张斐许向阳
Owner NANJING SIMCERE DONGYUAN PHARM CO LTD
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