Mass Spectrometry MRM Optimization Using Normalized Product-Ion Spectra
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Solution Overview
Problem
Conventional methods for optimizing Multiple Reaction Monitoring (MRM) measurement conditions for target compounds in samples from soil or living organisms are time-consuming and inefficient, especially when only a trace amount of sample is available, as they require multiple product-ion scan measurements across various precursor-ion and collision-energy-value combinations.
Innovation Solution
A method that involves creating measurement conditions for all combinations of precursor-ion and collision-energy-value candidates, performing a product-ion scan measurement and a reference measurement within the introduction time of the target compound, creating a peak function to represent the compound's introduction, normalizing the product-ion spectra using a normalization function, and optimizing the MRM measurement conditions within a single measurement sequence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple product-ion scan measurements are performed for all combinations of precursor-ion candidates and collision-energy-value candidates, then the MRM measurement condition can be optimized, but the measurement time becomes excessively long
Solution Approach 1:
The patent applies preliminary action by performing a product-ion scan measurement once to obtain all necessary product-ion spectra for all precursor-ion and collision-energy-value combinations before optimization. The system stores these spectra and uses them for subsequent optimization without requiring repeated measurements, thus completing the preparatory measurement phase in advance.
Solution Approach 2:
The patent uses copying by creating a library of product-ion spectra obtained from a single measurement. Instead of repeatedly measuring the same samples, the system copies and reuses the stored product-ion spectra for different precursor-ion candidates and collision-energy-value combinations during the optimization process, eliminating the need for multiple physical measurements.
2Measurement precision
If multiple product-ion scan measurements are performed for all combinations of precursor-ion candidates and collision-energy-value candidates, then the MRM measurement condition can be optimized, but the sample consumption increases
Solution Approach 1:
The patent performs the product-ion scan measurement once in advance to capture all necessary spectral information. This preliminary measurement obtains product-ion spectra for all potential precursor ions and collision energy values, storing them for subsequent optimization without requiring additional sample introduction or consumption.
Solution Approach 2:
The system creates a digital copy of the product-ion spectra from a single measurement. These copied spectra are then used repeatedly for optimizing different MRM conditions without requiring the physical sample to be reintroduced multiple times, thus minimizing sample consumption while maintaining optimization accuracy.
3Adaptability or versatility
If the target compound is isolated by chromatograph for product-ion scan measurement, then the measurement can be performed on complex samples, but the introduction time is limited and the quantity of target compound changes temporally
Solution Approach 1:
The patent performs the product-ion scan measurement during the chromatographic separation process itself, utilizing the time when the target compound is being introduced. By obtaining product-ion spectra in advance during this limited window, the system prepares all necessary data for optimization before the chromatographic run completes.
Solution Approach 2:
The system continuously monitors and collects product-ion spectra throughout the chromatographic separation process. Instead of pausing the chromatographic run for separate measurements, the useful action of detecting product ions continues uninterrupted during the compound introduction, maximizing data acquisition within the limited time window.
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 allows for the optimization of MRM measurement conditions within a short period, even with a trace amount of sample, by reducing the number of necessary measurements and improving accuracy through normalization, thereby enhancing detection sensitivity and efficiency.
Implementation Method 1
a collision cell for fragmenting the precursor ion into product ions
Data Source
AI summary
A mass spectrometry method includes: creating a plurality of measurement conditions corresponding to all combinations of precursor-ion candidates generated from the target compound and collision-energy-value candidates; performing a product-ion scan measurement using each of the plurality of measurement conditions and performing a plurality of reference measurements for detecting a predetermined kind of ion generated from the target compound under the same condition, within an introduction time during which the target compound is introduced; creating a peak function, which is a function representing a change in the amount of introduction of the target compound into the mass spectrometer within the introduction time, based on the result of the reference measurement; creating a normalization function for normalizing the amount of introduction of the target compound within the introduction time, based on the peak function; and normalizing the intensity of product-ion spectra obtained by the product-ion scan measurements performed for all combinations.