Phosphatidylalkanol Composition for NMR Quantification
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current LC-MS-based methods for quantifying phosphatidylalkanols like PEth in blood samples rely on precise weighing and purity of reference materials, leading to errors in concentration determination due to weighing errors and incomplete dissolution, necessitating improved compositions and production methods for more accurate and precise analysis.
Innovation Solution
A water-miscible composition comprising a phosphatidylalkanol with a deuterated aprotic polar solvent, allowing concentration determination by NMR without relying on precise weighing or purity, and including amphiphilic additives for enhanced solubility and stability, enabling non-destructive periodic monitoring and improved analytical accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If LC-MS-based methods use precise weighing and purity assessment of reference materials, then quantitative determination of phosphatidylalkanol can be achieved, but errors in concentration determination occur due to weighing errors and incomplete dissolution
Solution Approach 1:
The patent replaces the mechanical weighing system with an NMR-based quantification system. Instead of determining concentration through precise weighing of reference materials followed by LC-MS analysis, the invention uses NMR spectroscopy to directly quantify phosphatidylalkanol concentrations in biological samples. The NMR method utilizes the characteristic signals of phosphatidylcholine precursors and phosphatidylalkanol products to calculate concentrations without requiring physical weighing, thereby eliminating weighing errors and dissolution issues while maintaining measurement precision.
2Ease of manufacture
If reference solutions are prepared by precise weighing and dissolution in suitable solvents, then standard curves can be generated for quantification, but errors translate to determined concentration due to weighing-errors, purity assumptions, volume measurement errors, and incomplete dissolution
Solution Approach 1:
The invention replaces the entire mechanical preparation and measurement system for reference solutions with an NMR-based quantification approach. The method directly measures phosphatidylalkanol concentrations in biological samples using NMR spectroscopy, comparing the NMR signals of phosphatidylcholine precursors with those of phosphatidylalkanol products. This eliminates the need for preparing reference solutions through weighing and dissolution, thereby removing the sources of error associated with these procedures while maintaining ease of analysis.
3Measurement precision
If quantitative determination relies on analytical reference solutions with known concentration, then standard curves can be developed, but the process is time-consuming and prone to multiple error sources
Solution Approach 1:
The patent replaces the time-consuming process of preparing and validating analytical reference solutions with a direct NMR quantification method. The NMR approach allows for simultaneous quantification of phosphatidylcholine precursors and phosphatidylalkanol products in a single measurement, eliminating the need for separate standard curve preparations and multiple validation steps. This significantly reduces analysis time while maintaining or improving quantitative determination accuracy through the inherent precision of NMR spectroscopy.
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 composition facilitates precise and accurate determination of phosphatidylalkanol concentrations in blood samples, reducing errors and improving analytical reliability through NMR-based methods, allowing for more reliable assessment of historic ethanol consumption.
Implementation Method 1
A water-miscible composition comprising a phosphatidylalkanol with a deuterated aprotic polar solvent
Implementation Method 2
concentration determination by quantitative nuclear magnetic resonance spectroscopy (QNMR)
Data Source
Figure 1A~1C
Figure 2A~2C
Figure 3A~3B
AI summary
The present invention discloses a composition comprising a compound of formula I and a deuterated solvent. The deuterated solvent is miscible with water in any proportion at a temperature of 20 to 25 °C and comprises less than 5% residual 1H- isotopes. The concentration of the compound of formula I may advantageously be determined by 1H-QNMR. Methods of production of the composition and salts of compounds of formula I, as well as related analogs and novel reagents and intermediates for the production thereof,are also described.