Tetranor PGDM Biomarker Detection via HPLC/MS/MS

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Solution Overview

Problem

Current methods lack effective tools for assessing the biosynthesis of prostaglandin D2 (PGD2) in humans and mice, hindering research and clinical applications due to the absence of specific and sensitive methodologies for measuring PGD2 metabolites.

Innovation Solution

Development of a method to detect tetranor PGDM, a metabolite of PGD2, using high-pressure liquid chromatography/mass spectrometry (HPLC/MS/MS) for quantifying PGD2 levels in biological samples, allowing for non-invasive monitoring and clinical applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If classical metabolite measurement methods are used to assess PGD2 biosynthesis, then measurement capability is provided, but measurement precision and reliability are insufficient due to lack of specific and sensitive methodologies

Engineering Contradiction:
ImprovePGD2 level detection accuracyVSAvoidPGD2 biosynthesis assessment validity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent uses tetranor PGDM as an intermediary metabolite to indirectly measure PGD2 levels. Since PGD2 itself is unstable and difficult to measure directly, the stable metabolite tetranor PGDM serves as a mediator that reflects PGD2 biosynthesis activity, providing both precision and reliability in measurement

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces indirect clinical assessment methods with a direct biochemical measurement system using HPLC/MS/MS to quantify tetranor PGDM. This substitution of measurement approaches enables precise and reliable detection of PGD2 biosynthesis without relying on subjective clinical evaluations

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Adaptability or versatility

If no specific methodology for measuring PGD2 metabolites is available, then research and clinical applications are hindered, but developing such methodology requires complex analytical systems

Engineering Contradiction:
ImprovePGD2 monitoring application rangeVSAvoidanalytical system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent establishes a universal measurement platform using tetranor PGDM that can be applied across multiple scenarios including research settings, clinical diagnostics, and therapeutic monitoring. The same metabolite marker and analytical method serve diverse functions, from basic research to patient stratification and treatment response assessment

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

Solution Approach 2:

The patent transforms the measurement approach by changing from direct PGD2 detection to tetranor PGDM quantification. This parameter change enables the use of stable, measurable metabolites instead of unstable parent compounds, simplifying the analytical process while expanding application versatility

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If existing metabolite assays are used, then some measurement capability is achieved, but sensitivity and specificity are insufficient for accurate PGD2 level quantification

Engineering Contradiction:
ImprovePGD2 metabolite quantification accuracyVSAvoidmetabolite detection challenge
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent employs tetranor PGDM as a stable intermediary metabolite that mediates between the unstable PGD2 and the detection system. This intermediary approach resolves the detection challenge by providing a measurable surrogate that maintains sensitivity and specificity for PGD2 quantification

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a measurable copy of PGD2 through its metabolite tetranor PGDM. Instead of directly detecting the unstable parent compound, the method measures a stable molecular copy that preserves the essential information about PGD2 biosynthesis, thereby overcoming detection difficulties

Inventive Principle:
Principle #26Copying

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

The method provides a sensitive and specific molecular marker for PGD2 levels, enabling research and clinical applications, including monitoring acute vascular injury, assessing risk of acute myocardial infarction, and identifying candidates for PGD2 suppression therapy.

Implementation Method 1

using high-pressure liquid chromatography/mass spectrometry (HPLC/MS/MS) for quantifying PGD2 levels in biological samples

Methodology Applied
Scientific EffectHigh-pressure liquid chromatography: Chromatography

Implementation Method 2

using high-pressure liquid chromatography/mass spectrometry (HPLC/MS/MS) for quantifying PGD2 levels in biological samples

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS8785682B2Tetranor PGDM: a biomarker of PGD<sub>2 </sub>synthesis in vivo
Publication Date: 2014.07.22 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US8785682B2 patent drawing
  • US8785682B2 patent drawing
  • US8785682B2 patent drawing

AI summary

The present invention relates to a prostaglandin D2 metabolite, derivatives thereof, compositions comprising the metabolite, and an antibody that specially binds to the metabolite. Methods of use are also provided.