Teriflunomide Mass Spectrometry Assay for Precise Plasma Quantitation
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Solution Overview
Problem
Current methods for detecting and quantifying teriflunomide, a metabolite of leflunomide, are not sufficiently efficient or accurate, particularly in biological samples like plasma or serum.
Innovation Solution
The use of mass spectrometry, including tandem mass spectrometry, to detect and quantify teriflunomide by ionizing samples and determining the amount of specific ions, with fragmentation and selection of fragment ions to confirm the presence and amount of teriflunomide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry is used to detect and quantify teriflunomide, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The mass spectrometry method is divided into distinct operational phases: ionization of the sample, selection of precursor ions based on specific m/z ratios, fragmentation of selected ions, and detection of fragment ions. This segmentation allows each step to be optimized independently while maintaining overall system manageability despite the inherent complexity of mass spectrometry
Solution Approach 2:
The patent uses specific ionization techniques (electrospray ionization or atmospheric pressure chemical ionization) as intermediary processes that convert neutral teriflunomide molecules into charged ions suitable for mass spectrometric analysis. This intermediary step enables the detection of teriflunomide at very low concentrations (2.5-5000 ng/mL range) with high precision while managing the complexity through standardized ionization protocols
2Measurement precision
If tandem mass spectrometry with fragmentation is used, then measurement precision is improved, but analysis time increases
Solution Approach 1:
The method performs preliminary selection of precursor ions based on their specific mass-to-charge ratios before fragmentation. By pre-selecting only the relevant teriflunomide precursor ions (and excluding other substances), the system reduces the complexity of subsequent fragmentation analysis and focuses computational and analytical resources only on the ions of interest, thereby reducing overall analysis time while maintaining high precision
Solution Approach 2:
The mass spectrometry system dynamically adjusts its operation between different modes: first selecting precursor ions based on m/z ratio, then fragmenting selected ions, and finally detecting specific fragment ions. This dynamic, multi-stage approach allows the system to optimize analysis time by only processing ions that meet selection criteria, rather than analyzing all ions in the sample
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 allows for precise detection and quantification of teriflunomide in biological samples, with the ability to detect levels within the range of 2.5 ng/ml to 5000 ng/mL, and to confirm the effectiveness of cholestyramine drug elimination procedures.
Implementation Method 1
subjecting the sample to ionization under conditions suitable to produce one or more ions detectable by mass spectrometry
Implementation Method 2
fragmenting a teriflunomide precursor ion to produce one or more fragment ions
Data Source
AI summary
A method for determining an amount of teriflunomide in a sample by mass spectrometry includes adding an internal standard to the sample, subjecting the sample to solid phase extraction, purifying the sample by high turbulence liquid chromatography, ionizing the sample to produce one or more teriflunomide ions detectable by mass spectrometry, determining the amount of the one or more teriflunomide ions by mass spectrometry, and using the amount of the one or more ions determined to further determine the amount of teriflunomide in the sample.