LC-MS Mobile Phase Additive for Phosphate Adsorption Prevention

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Solution Overview

Problem

Compounds with a phosphate group, such as nucleotides, cause metal adsorption in liquid chromatography systems, leading to reduced detection sensitivity and accuracy in mass spectrometry.

Innovation Solution

Perform liquid chromatography using a mobile phase containing oxalic acid or its salt to prevent adsorption of compounds with phosphate groups to metal surfaces, followed by mass spectrometry using an electrospray ionization method.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a mobile phase containing formic acid is used in liquid chromatography, then the analysis can be performed with standard conditions, but compounds with phosphate groups cause metal adsorption on piping leading to reduced detection sensitivity

Engineering Contradiction:
Improvestandard analysis conditionVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent introduces oxalic acid as an intermediary substance in the mobile phase to prevent metal adsorption of phosphate-containing compounds. The oxalic acid acts as a mediator that competes for metal binding sites on the piping surface, thereby preventing the phosphate groups from adsorbing to metal surfaces and maintaining detection sensitivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical composition parameter of the mobile phase by adding oxalic acid to the formic acid-based mobile phase. This parameter change modifies the chemical environment in the system to prevent unwanted metal adsorption while maintaining the chromatographic separation capabilities.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If compounds with phosphate groups adsorb to metal surfaces in the liquid chromatography system, then metal adsorption occurs, but this leads to reduced detection sensitivity and accuracy in mass spectrometry

Engineering Contradiction:
Improveprevention of metal adsorptionVSAvoiddetection sensitivity and accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by adding oxalic acid to the mobile phase before the analysis begins. This pre-treatment ensures that the metal surfaces in the piping are already occupied by oxalic acid, preventing phosphate-containing compounds from adsorbing during the subsequent chromatographic run and mass spectrometry analysis.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If oxalic acid is added to the mobile phase to prevent metal adsorption, then detection sensitivity is improved, but the mobile phase composition becomes more complex

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmobile phase composition
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent modifies the mobile phase composition by adding oxalic acid to the existing formic acid-based system. This parameter change improves detection sensitivity by preventing metal adsorption while maintaining relative simplicity in the mobile phase formulation.

Inventive Principle:
Principle #35Parameter changes

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

Enhances the detection sensitivity and accuracy of compounds with phosphate groups, allowing for high-quality analysis in mass spectrometry.

Implementation Method 1

a mobile phase including an adsorption prevention agent for preventing adsorption of a sample including a compound having a phosphate group to metal in a stationary phase

Methodology Applied
Scientific EffectAdsorption prevention: Adsorption

Implementation Method 2

in the mass spectrometry, the sample is preferably ionized by an electrospray method

Methodology Applied
Scientific EffectElectrospray ionization: Ionisation

Data Source

PatentUS12354860B2Analysis method, adsorption prevention agent, and analysis kit
Publication Date: 2025.07.08 SHIMADZU CORP
  • US12354860B2 patent drawing
  • US12354860B2 patent drawing
  • US12354860B2 patent drawing

AI summary

An analysis method includes: performing liquid chromatography using a mobile phase including an adsorption prevention agent for preventing adsorption of a sample including a compound having a phosphate group to metal; and performing mass spectrometry on an eluate of the liquid chromatography. The adsorption prevention agent includes an oxalic acid or a salt of the oxalic acid.