Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

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

A liquid chromatography and chiral chromatographic column technology 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, achieve reduction of interference, Guaranteed solubility and quality controllable effect

Active Publication Date: 2008-12-24
AVENTIS PHARMA HAINAN
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] 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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Instruments and Conditions

[0037] Shimadzu high performance liquid chromatography; column: Daicel OD-RH chiral column (150mm×4.6mm)

[0038] Mobile phase: (0.05mol / L potassium dihydrogen phosphate, 10% phosphoric acid to adjust pH to 3.0)-acetonitrile=85:15

[0039] Detection wavelength: 287nm; Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10μl

[0040] Experimental steps:

[0041] Take (R,S)-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, and use a flow Phase diluted to the mark, shake well, as the test solution;

[0042] Get need testing solution, carry out high performance liquid chromatography analysis by above-mentioned condition, record chromatogram, the result sees figure 1 .

[0043] 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...

Embodiment 2

[0045] Instruments and Conditions

[0046] Shimadzu high performance liquid chromatography; column: Daicel OD-RH chiral column (150mm×4.6mm)

[0047] Mobile phase: (0.02mol / L potassium dihydrogen phosphate, 10% phosphoric acid to adjust pH to 3.8)-acetonitrile=80:20

[0048]Detection wavelength: 287nm; Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10μl

[0049] Experimental steps:

[0050] Take (R,S)-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, and use a flow Phase diluted to the mark, shake well, as the test solution;

[0051] 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 c...

Embodiment 3

[0053] Instruments and Conditions

[0054] Shimadzu high performance liquid chromatography; column: Daicel OD-RH chiral column (150mm×4.6mm)

[0055] Mobile phase: (0.05mol / L sodium acetate, glacial acetic acid to adjust pH to 2.5)-acetonitrile=75:25

[0056] Detection wavelength: 287nm; Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10μl

[0057] Experimental steps:

[0058] Take (R,S)-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, and use a flow Phase diluted to the mark, shake well, as the test solution;

[0059] 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 p...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
wavelengthaaaaaaaaaa
separationaaaaaaaaaa
separationaaaaaaaaaa
Login to View More

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] (R, S)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid is th...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/04C07B57/00B01D15/38B01J20/29
Inventor 胡杨
Owner AVENTIS PHARMA HAINAN
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com