Succinylacetone Detection via Mild Derivatization
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Solution Overview
Problem
Current methods for detecting succinylacetone, a key marker for hereditary tyrosinemia Type I, are hindered by its reactivity, which complicates extraction and analysis, often requiring harsh conditions that can also extract and alter other metabolites, making it difficult to obtain accurate metabolic profiles.
Innovation Solution
A method involving a C1-3 linear or branched chain monoalcohol and a strong base, such as hydrazine, is used to derivatize succinylacetone, allowing for its extraction and analysis alongside other metabolites like amino acids and acylcarnitines using tandem mass spectrometry, without altering their ratios, under mild conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If harsh extraction conditions (extreme acidity and high temperature) are used to extract succinylacetone, then extraction efficiency is improved, but other metabolites are altered and metabolic profile accuracy deteriorates
Solution Approach 1:
The patent changes the extraction parameters from harsh conditions (extreme acidity, high temperature) to mild conditions (neutral pH, room temperature) by using a specific extraction solution formulation. This allows succinylacetone to be extracted efficiently without altering other metabolites, thus maintaining metabolic profile accuracy while achieving good extraction efficiency.
Solution Approach 2:
The patent introduces an intermediary extraction solution that selectively facilitates succinylacetone extraction while being compatible with other metabolites. The extraction solution acts as a mediator that enables simultaneous extraction of succinylacetone and other metabolites under mild conditions, preventing the harmful effects of harsh conditions on the metabolic profile.
2Difficulty of detecting and measuring
If succinylacetone is extracted using conventional methods, then detection capability is improved, but the reactivity of succinylacetone complicates the extraction process
Solution Approach 1:
The patent performs preliminary derivatization of succinylacetone before extraction to convert it into a more stable and detectable form. This preliminary action simplifies the subsequent extraction and detection processes by reducing the reactivity-related complications, while maintaining high detection capability for succinylacetone.
3Adaptability or versatility
If concurrent extraction of multiple metabolites is performed, then comprehensive metabolic profiling is improved, but extraction selectivity for succinylacetone may be compromised
Solution Approach 1:
The patent develops a universal extraction solution that can simultaneously extract multiple metabolites including succinylacetone, amino acids, and other compounds under mild conditions. This multi-functional extraction approach maintains selectivity for succinylacetone while enabling comprehensive metabolic profiling, as the extraction solution is designed to be compatible with all target analytes.
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 the concurrent extraction and analysis of succinylacetone and other metabolites, providing accurate metabolic profiles and facilitating early detection of hereditary tyrosinemia Type I, while avoiding harsh extraction conditions that might distort the metabolic landscape.
Implementation Method 1
derivatizing a biologically active ketone in the sample
Implementation Method 2
evaluating the derivatized biologically active ketone in the derivatized sample using tandem mass spectrometry
Implementation Method 3
contacting a sample with an extraction solution comprising a C1-3 linear or branched chain monoalcohol and a strong base
Data Source
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AI summary
This invention relates, inter alia, to detecting and/or measuring succinylacetone and one or more additional biological analytes using mass spectrometry, e.g., tandem mass spectrometry, by derivatizing succinylacetone in a sample by contacting the sample with an extraction solution comprising a C1-3 linear or branched chain monoalcohol and a strong base selected from the group consisting of hydrazine, a modified hydrazine, and hydroxylamine.