Tandem Mass Spectrometry for Precise Vitamin A and E Quantification

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Solution Overview

Problem

Current methods for measuring vitamin A, α-tocopherol, and β/γ-tocopherol are limited in accuracy and efficiency, particularly in distinguishing between these compounds and determining their combined amounts in biological samples.

Innovation Solution

The use of tandem mass spectrometry with ionization techniques like APCI in positive ion mode, combined with liquid chromatography, allows for the detection and quantification of vitamin A, α-tocopherol, and the combined amount of β-tocopherol and γ-tocopherol by fragmenting specific precursor ions into detectable fragment ions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods (HPLC with photodiode array detection or single mass spectrometry) are used for measuring vitamin A, α-tocopherol, and β/γ-tocopherol, then the measurement process is simpler, but the accuracy and precision in distinguishing and quantifying these compounds is insufficient

Engineering Contradiction:
Improveaccuracy of vitamin detectionVSAvoidcomplexity of detection system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the detection process into two distinct mass spectrometry stages: first mass spectrometry for initial ion detection and second mass spectrometry for fragment ion detection. This segmentation enables precise differentiation of vitamin compounds through sequential mass analysis, resolving the contradiction between measurement precision and device complexity by using a tandem MS system that systematically breaks down the detection task.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses collision-induced dissociation as an intermediary process between the first and second mass spectrometry stages. This intermediary mechanism converts precursor ions into characteristic fragment ions, serving as a mediator that enables precise compound identification. The collision cell acts as an intermediary component that transforms the detection challenge into a solvable problem through controlled fragmentation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of information

If conventional single-stage mass spectrometry is used, then the device complexity is lower, but the ability to distinguish between vitamin compounds and determine their combined amounts is limited

Engineering Contradiction:
Improveinformation on compound distinctionVSAvoidcomplexity of mass spectrometry system
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The detection system is segmented into two sequential mass analysis stages. The first mass spectrometry stage captures precursor ion information, while the second stage captures fragment ion information. This segmentation preserves complete structural information about vitamin compounds that would be lost in single-stage detection, directly addressing the information loss problem while managing system complexity through modular architecture.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent adds a temporal dimension to the mass spectrometry detection by implementing sequential two-stage analysis. Instead of attempting to detect all compound characteristics simultaneously in one stage, the system progresses through time: first detecting precursor ions, then detecting fragment ions. This dimensional approach to detection prevents information loss while keeping each individual detection stage relatively simple.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Productivity

If conventional HPLC with photodiode array detection is used, then the equipment is simpler, but the throughput and precision of vitamin analysis in clinical settings is insufficient

Engineering Contradiction:
Improvethroughput of vitamin analysisVSAvoidprecision of vitamin quantification
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The tandem mass spectrometry system performs multiple functions: it identifies vitamin compounds through precursor ion detection, quantifies them through fragment ion detection, and distinguishes between different vitamin types (vitamin A, α-tocopherol, β/γ-tocopherol) in a single analytical run. This multi-functionality increases throughput compared to conventional methods that would require separate analyses for each function, while maintaining high precision through the dual-stage detection approach.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 method provides accurate and simultaneous detection and quantification of these vitamins in biological samples, improving the precision and throughput of vitamin A, α-tocopherol, and β/γ-tocopherol analysis, especially in clinical settings.

Implementation Method 1

subjecting the sample to ionization under conditions suitable to produce one or more ions detectable by mass spectrometry

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

determining the amount of said one or more ions by tandem mass spectrometry

Methodology Applied
Scientific EffectFragmentation:

Data Source

PatentUS12174203B2Detection of vitamins a and e by tandem mass spectrometry
Publication Date: 2024.12.24 QUEST DIAGNOSTICS INVESTMENTS INC
  • US12174203B2 patent drawing
  • US12174203B2 patent drawing
  • US12174203B2 patent drawing

AI summary

Methods are described for measuring the amount of one or more of vitamin A, α-tocopherol, and the combination of β-tocopherol and γ-tocopherol in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying one or more of vitamin A, α-tocopherol, and the combination of β-tocopherol and γ-tocopherol in a sample.