Method for separating and detecting nebivolol hydrochloride impurity by liquid phase chromatography

A technology of high performance liquid chromatography and intermediates, which is applied in the field of separation and determination of R-type and S-type optical isomers of nebivolol intermediate-4, which can solve problems such as undiscovered, reduce interference, and ensure Solubility, Quality Controlled Effects

Active Publication Date: 2011-09-14
AVENTIS PHARMA HAINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] After searching, nothing about R-6-fluoro-3,4-dihydro-2H-1-chromene-2-carboxylic acid and S-6-fluoro-3,4-dihydro-2H-1 -Chrene-2-carboxylic acid two kinds of optical isomer separation and determination method reported in the literature

Method used

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  • Method for separating and detecting nebivolol hydrochloride impurity by liquid phase chromatography
  • Method for separating and detecting nebivolol hydrochloride impurity by liquid phase chromatography
  • Method for separating and detecting nebivolol hydrochloride impurity by liquid phase chromatography

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Experimental program
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Effect test

Embodiment 1

[0033] Instruments and Conditions

[0034] Shimadzu high performance liquid chromatography; column: Daicel OD-RH chiral column (150mm×4.6mm)

[0035] Mobile phase: (0.05mol / L potassium dihydrogen phosphate, 10% phosphoric acid to adjust pH to 3.0)-acetonitrile=85:15

[0036] Detection wavelength: 287nm; Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10μl

[0037] Experimental steps:

[0038] Take (RS)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid racemate 10mg, put it in a 20ml measuring bottle, add about 2ml of methanol to dissolve, dilute with mobile phase To the scale, shake well, as the test solution;

[0039] Get need testing solution, carry out high performance liquid chromatography analysis by above-mentioned condition, record chromatogram, the result sees figure 1 .

[0040] figure 1 The chromatographic peak with a retention time of 21.967 minutes is the chromatographic peak of S-6-fluoro-3,4-dihydro-2H-1-chromene-2-carboxylic acid, an...

Embodiment 2

[0042] Instruments and Conditions

[0043] Shimadzu high performance liquid chromatography; column: Daicel OD-RH chiral column (150mm×4.6mm)

[0044] Mobile phase: (0.02mol / L potassium dihydrogen phosphate, 10% phosphoric acid to adjust pH to 3.8)-acetonitrile=80:20

[0045] Detection wavelength: 287nm; Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10μl

[0046] Experimental steps:

[0047]Take (RS)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid racemate 10mg, put it in a 20ml measuring bottle, add about 2ml of methanol to dissolve, dilute with mobile phase To the scale, shake well, as the test solution;

[0048] Get need testing solution, carry out high performance liquid chromatography analysis by above-mentioned condition, record chromatogram, the result sees figure 2 . figure 2 The chromatographic peak whose retention time is 9.667 minutes is the chromatographic peak of S-6-fluoro-3,4-dihydro-2H-1-chromene-2-carboxylic acid, and the chrom...

Embodiment 3

[0050] Instruments and Conditions

[0051] Shimadzu high performance liquid chromatography; column: Daicel OD-RH chiral column (150mm×4.6mm)

[0052] Mobile phase: (0.05mol / L sodium acetate, glacial acetic acid to adjust pH to 2.5)-acetonitrile=75:25

[0053] Detection wavelength: 287nm; Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10μl

[0054] Experimental steps:

[0055] Take (RS)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid racemate 10mg, put it in a 20ml measuring bottle, add about 2ml of methanol to dissolve, dilute with mobile phase To the scale, shake well, as the test solution;

[0056] Get need testing solution, carry out high performance liquid chromatography analysis by above-mentioned condition, record chromatogram, the result sees image 3 . image 3 The chromatographic peak whose retention time is 25.333 minutes is the chromatographic peak of S-6-fluoro-3,4-dihydro-2H-1-chromene-2-carboxylic acid, and the chromatographic peak ...

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Abstract

The invention discloses a method for measuring nebivolol hydrochloride impurities by a liquid phase chromatography method. Cellulose three(3, 5-dimethylphenyl amino formate is taken as a chiral chromatographic column of a filling material, and a mixed solution of a buffer salt solution and an organic phase according to certain ratio is taken as a mobile phase. The method can rapidly and accurately separate and measure the two optical isomers.

Description

technical field [0001] The invention relates to a high-performance liquid chromatography, especially a method for separating and measuring two optical isomers of R-type and S-type of nebivolol intermediate-4. Background technique [0002] Nebivolol (Nibivolol) is a cardioselective β-receptor blocker with vasodilator effect, mainly used in the treatment of essential hypertension, it has the advantages of significant curative effect, convenient administration, less adverse reactions, etc. , is a new promising antihypertensive drug. Nebivolol was originally developed by Johnson Corporation of the United States for the treatment of essential hypertension. [0003] Nebivolol has four chiral carbon atoms, a total of eight isomers, and the drug target product for the treatment of essential hypertension is a pair of enantiomers, namely D-Nibivolol and L-Nibivolol A mixture of DL-Nibivolol (DL-Nibivolol). [0004] (RS)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid is the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D311/04C07B57/00B01D15/38B01J20/29
Inventor 胡杨
Owner AVENTIS PHARMA HAINAN
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