Crown Ether Chromatography for Amine Retention in Low-Water Phases

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Solution Overview

Problem

Existing chromatography methods using stationary phases with crown ether-like cyclic structures struggle to achieve high separation performance for amines when using mobile phases with low water content, as they lack sufficient retention force and are prone to ghost peaks from strong acids like trifluoroacetic acid.

Innovation Solution

The method involves using a mobile phase with a salt of a cation and an acid anion at specific concentrations and low water content, promoting amine retention through ion pairing with the ammonium group in the stationary phase.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a mobile phase with low water content is used, then the chromatography system becomes more suitable for LC-MS applications and reduces ghost peaks, but the retention force for amines becomes insufficient

Engineering Contradiction:
Improveseparation performanceVSAvoidretention force
Core Design Contradiction:
ReliabilityVSForce

Solution Approach 1:

The patent introduces an intermediary substance (salt of a cation and acid anion) that mediates between the low water content mobile phase and the amine analyte. This salt provides the necessary ionic interaction to enable retention of amines on the crown ether stationary phase even in low water content conditions, thus resolving the contradiction between reduced ghost peaks and maintained retention force

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the mobile phase by specifying precise concentrations of the salt (0.2-50.0 mM) and water content (50 vol.% or less). This parameter optimization enables the system to achieve both low ghost peak noise and sufficient retention force simultaneously, resolving the contradiction through quantitative control

Inventive Principle:
Principle #35Parameter changes

2Force

If a strong acid like perchloric acid is used in the mobile phase, then the retention force for amines is enhanced, but the system becomes difficult to handle due to strong oxidizing properties

Engineering Contradiction:
Improveretention forceVSAvoidhandling difficulty
Core Design Contradiction:
ForceVSEase of operation

Solution Approach 1:

The patent replaces the problematic strong acid (perchloric acid) with a safer alternative salt system that provides equivalent retention functionality without the hazardous oxidizing properties. This substitution eliminates the handling difficulty while maintaining the necessary retention force for amine separation

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent uses a salt of cation and acid anion as an intermediary to provide the ionic interaction needed for amine retention without requiring strong acids. This intermediary approach delivers the necessary retention force while avoiding the safety issues associated with perchloric acid

Inventive Principle:
Principle #24Intermediary (Mediator)

3Force

If trifluoroacetic acid is used at high concentration in the mobile phase, then amine retention is improved, but ghost peaks appear due to adsorption on chromatograph components

Engineering Contradiction:
Improveretention forceVSAvoidghost peaks
Core Design Contradiction:
ForceVSObject-generated harmful factors

Solution Approach 1:

The patent replaces trifluoroacetic acid with a salt-based retention mechanism that eliminates ghost peak formation. The salt system provides sufficient retention force without the adsorption issues that cause ghost peaks, thus resolving the contradiction between improved retention and eliminated harmful artifacts

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent converts the harmful effect of acid adsorption (which causes ghost peaks) into a beneficial salt-based ionic interaction system. By using a salt of cation and acid anion, the system achieves retention through controlled ionic forces without the uncontrolled adsorption that generates ghost peaks

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach achieves high separation performance for amines, even in low water content mobile phases, reducing ghost peaks and improving retention, suitable for applications like LC-MS.

Implementation Method 1

retention of an amine in a stationary phase is promoted, and efficient separation of the amine can be realized

Methodology Applied
Scientific EffectIon pairing: Ion Repulsion/Attraction

Data Source

PatentEP4578848A1Amine separation method
Publication Date: 2025.07.02 DAICEL CORP
  • EP4578848A1 patent drawingFigure 1~2
  • EP4578848A1 patent drawingFigure 3~4
  • EP4578848A1 patent drawingFigure 5~6

AI summary

Provided is an amine separation method that includes separating an amine through chromatography using a stationary phase including a ligand having a crown ether-like cyclic structure and being supported on a carrier; and a mobile phase containing a salt of a cation and an acid anion at a concentration of 0.2 mM or more and 50.0 mM or less and containing a solvent having a water content of 50 vol.% or less.