Lipid Oxidation Analysis Using LC-MS Ion Ratio Normalization

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Solution Overview

Problem

Current methods for evaluating the quality of stored samples, particularly in lipid analysis, lack the ability to quantitatively assess the degree of oxidation, which is crucial for accurate analysis and medical diagnosis.

Innovation Solution

An analysis method involving liquid chromatography followed by mass spectrometry to detect ions corresponding to cholesteryl ester and cholesteryl ester peroxide, calculating a degree of oxidation based on the intensity ratio of these ions, and normalizing sample-derived ion intensities using specific lipid molecules to ensure accurate comparison across samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If mass spectrometry is performed to detect lipid molecules in stored samples, then lipid composition analysis can be conducted, but the degree of oxidation cannot be quantitatively evaluated

Engineering Contradiction:

Improvequantitative evaluation of oxidation degreeVSAvoidoxidation status information

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent segments the detection process into two distinct mass spectrometry measurements: first mass spectrometry for detecting cholesteryl ester ions (intact molecules) and second mass spectrometry for detecting cholesteryl ester peroxide ions (oxidized products). This segmentation enables separate quantification of oxidation products versus intact molecules, providing quantitative oxidation degree evaluation that was previously unattainable with single-stage mass spectrometry.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the detection parameter from simple lipid molecule identification to ratio-based quantification. By calculating the ratio between the intensity of cholesteryl ester peroxide ions (oxidized) and cholesteryl ester ions (intact), the system transforms qualitative detection into quantitative oxidation assessment. This parameter change enables precise measurement of oxidation degree while maintaining compatibility with existing mass spectrometry infrastructure.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If sample-derived ion intensities are used directly for comparison across samples, then analysis is simplified, but variations in sample concentration and composition lead to inaccurate comparisons

Engineering Contradiction:

Improvesimplicity of analysisVSAvoidaccuracy of sample comparison

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent introduces an internal standard substance as an intermediary reference. This internal standard serves as a mediator between variable sample conditions and the measurement process. By normalizing sample-derived ion intensities against the internal standard's ion intensity, the system compensates for variations in sample concentration, injection volume, and instrument response, enabling accurate cross-sample comparisons while maintaining operational simplicity.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Device complexity

If only cholesteryl ester is monitored in mass spectrometry, then the analysis is straightforward, but oxidation products cannot be detected

Engineering Contradiction:

Improvesimplicity of detection methodVSAvoidquality assessment accuracy

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The patent implements periodic action through sequential mass spectrometry measurements. The system performs first mass spectrometry to detect cholesteryl ester ions, then performs second mass spectrometry to detect cholesteryl ester peroxide ions. This periodic, two-stage detection approach maintains relative simplicity by using the same instrument twice rather than requiring complex simultaneous multi-target detection, while reliably capturing both intact and oxidized lipid species for comprehensive quality assessment.

Inventive Principle:

Principle #19Periodic action

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 enables quantitative evaluation of sample oxidation, enhancing the quality assessment of stored samples and improving the reliability of lipid analysis for medical diagnostics.

Implementation Method 1

subjecting a sample to liquid chromatography

Methodology Applied

Scientific EffectChromatography: Chromatography

Implementation Method 2

performing first mass spectrometry of the sample subjected to the liquid chromatography to detect a first ion corresponding to cholesteryl ester and a second ion corresponding to cholesteryl ester peroxide

Methodology Applied

Scientific EffectIonization: Ionisation

Data Source

PatentUS11860138B2Analysis method and analytical device

Publication Date: 2024.01.02 SHIMADZU CORP

AI summary

An analysis method includes: subjecting a sample to liquid chromatography; performing first mass spectrometry of the sample subjected to the liquid chromatography to detect a first ion corresponding to cholesteryl ester and a second ion corresponding to cholesteryl ester peroxide; and analyzing a degree of oxidation of the sample based on a ratio between an intensity of the detected first ion and an intensity of the detected second ion.