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

High performance liquid chromatography-based method for separating and detecting sacubitril intermediate and optical isomers thereof

A technology of high performance liquid chromatography and optical isomers, which is applied in the field of separation and detection of sacubitril intermediates and their optical isomers, can solve the difficulties in the separation and detection of optical isomers and the quality control of separated preparations and other issues to achieve the effect of ensuring quality controllability, ensuring stability, and improving symmetry

Inactive Publication Date: 2017-05-31
江苏开元医药有限公司 +1
View PDF3 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the separation of optical isomers with chiral carbon atoms (especially multiple chiral carbon atoms) has always been a difficult point in the synthesis of chiral drugs and the quality control of preparations
After searching the literature, there is no report on the separation and detection method of AHU08 and its optical isomers

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
  • High performance liquid chromatography-based method for separating and detecting sacubitril intermediate and optical isomers thereof
  • High performance liquid chromatography-based method for separating and detecting sacubitril intermediate and optical isomers thereof
  • High performance liquid chromatography-based method for separating and detecting sacubitril intermediate and optical isomers thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Separation and detection of AHU08 and its optical isomers.

[0027] Instruments and Conditions:

[0028] High performance liquid chromatograph: Thermo U3000 (Thermo company);

[0029] Chromatographic column: CHIRALPAK AD-H chiral column (250mm×4.6mm, 5μm) (Daicel Company);

[0030] Mobile phase: n-hexane: ethanol: trifluoroacetic acid=92:8:0.1 (v / v / v);

[0031] Flow rate: 1.0ml / min;

[0032] Column temperature: 35°C;

[0033] Detection wavelength: 254nm;

[0034] Injection volume: 10 μl.

[0035] Implementation steps:

[0036] Weigh 2mg each of AHU08, Isomer1, Isomer 2, and Isomer 3, place them in a 20ml volumetric flask, add mobile phase to dissolve and dilute to the mark, shake well, and use it as a system suitability solution. Take AHU08 10mg, accurately weighed, place in a 20ml volumetric flask, add mobile phase to dissolve and dilute to the mark, as the test solution.

[0037] Measure 10 μl of the system suitability solution, inject it into the l...

Embodiment 2

[0039] Example 2: Separation and detection of AHU08 and its optical isomers.

[0040] Instruments and Conditions:

[0041] High performance liquid chromatograph: Thermo U3000 (Thermo company);

[0042] Chromatographic column: CHIRALPAK AD-H chiral column (250mm×4.6mm, 5μm) (Daicel company)

[0043] Mobile phase: n-hexane: ethanol: trifluoroacetic acid=92:8:0.3 (v / v / v);

[0044] Flow rate: 1.0ml / min;

[0045] Column temperature: 35°C;

[0046] Detection wavelength: 254nm;

[0047] Injection volume: 10 μl.

[0048] Implementation steps:

[0049] Weigh 2mg each of AHU08, Isomer1, Isomer 2, and Isomer 3, place them in a 20ml volumetric flask, add mobile phase to dissolve and dilute to the mark, shake well, and use it as a system suitability solution. Take AHU08 10mg, accurately weighed, place in a 20ml volumetric flask, add mobile phase to dissolve and dilute to the mark, as the test solution.

[0050] Measure 10 μl of the system suitability solution, inject it into the li...

Embodiment 3

[0052] Example 3: Separation and detection of AHU08 and its optical isomers.

[0053] Instruments and Conditions:

[0054] High performance liquid chromatograph: Thermo U3000 (Thermo company);

[0055] Chromatographic column: CHIRALPAK AD-H chiral column (250mm×4.6mm, 5μm) (Daicel company)

[0056] Mobile phase: n-hexane: ethanol: trifluoroacetic acid=92:8:0.5 (v / v / v);

[0057] Flow rate: 1.0ml / min;

[0058] Column temperature: 35°C;

[0059] Detection wavelength: 254nm;

[0060] Injection volume: 10 μl.

[0061] Implementation steps:

[0062] Weigh 2mg each of AHU08, Isomer1, Isomer 2, and Isomer 3, place them in a 20ml volumetric flask, add mobile phase to dissolve and dilute to the mark, shake well, and use it as a system suitability solution. Take AHU08 10mg, accurately weighed, place in a 20ml volumetric flask, add mobile phase to dissolve and dilute to the mark, as the test solution.

[0063] Measure 10 μl of the system suitability solution, inject it into the li...

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
Login to View More

Abstract

The invention belongs to the technical field of pharmaceutical analysis, and relates to a high performance liquid chromatography-based method for separating and detecting a sacubitril intermediate and optical isomers thereof. The separation and detection method which adopts chiral column using silica gel coated with an amylose derivative as a stationary phase and adopts a non-polar mixed solvent as a mobile phase, realizes simple, rapid and accurate separation and detection of AHU08 and the optical isomers (impurities) thereof, and solves the separation and detection problem of raw materials and preparations containing the AHU08 and the optical isomers thereof in order to ensure the quality controllability of sacubitril and compositions or preparations containing the sacubitril.

Description

technical field [0001] The invention belongs to the technical field of drug analysis, and relates to a method for separating and detecting sacubitril intermediates and optical isomers thereof based on high performance liquid chromatography. Background technique [0002] The anti-heart failure drug Entresto (code-named LCZ696) developed by Swiss Novartis pharmaceutical company is a dual inhibitor of angiotensin II receptor and neprilysin, which contains equimolar valsartan (valsartan) and sacubitril ( sacubitril). [0003] [0004] (2R,4S)-5-(biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid (code AHU08) is the key intermediate for the synthesis of sacubitril , there are two chiral centers in its molecular structure, so there are often three other optical isomer impurities in AHU08, which are Isomer1 (2S, 4S) as an epimer and Isomer2 as an epimer (2R,4R) and Isomer3 (2S,4R) as enantiomers (structure shown below). These optical isomer impurities will r...

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
IPC IPC(8): G01N30/60G01N30/30G01N30/32
CPCG01N30/60G01N30/30G01N30/32G01N2030/324
Inventor 燕立波王燕金永华
Owner 江苏开元医药有限公司
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