Post-Column Infused Internal Standards for LC-MS Matrix Effect Correction
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Solution Overview
Problem
Current methods for correcting matrix effects in liquid chromatography-mass spectrometry (LC-MS) are inadequate, especially in untargeted analysis, as they rely on stable isotope analogues which are not always available or practical, and fail to account for nonlinear matrix effects, leading to unreliable quantitation across different sample sources and instruments.
Innovation Solution
A method involving the induction of matrix effects on analytes and post-column infused internal standards, with test matrices added after separation, to match and correct for matrix effects, allowing for accurate quantitation even without reference standards or stable isotopes, by storing analyte-matched internal standard responses in a library for application across samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If stable isotope analogues are used as internal standards for matrix effect correction, then quantification accuracy is improved for targeted analysis, but the method becomes inapplicable or impractical for untargeted analysis and compounds without available standards
Solution Approach 1:
The patent replaces expensive, specialized stable isotope internal standards with common, easily obtainable compounds that can be added post-column. These surrogate internal standards serve the correction function without requiring isotopic labeling, making the approach universally applicable to any analyte regardless of availability of reference materials.
Solution Approach 2:
The patent introduces post-column infused internal standards as intermediary substances that mediate the correction of matrix effects. These standards are added after separation and co-elute with analytes, serving as proxies that capture matrix effect variability without requiring prior knowledge of analyte identity or structure.
2Reliability
If current matrix effect correction methods are used, then correction is possible for known compounds with available standards, but the method fails to account for nonlinear matrix effects and produces unreliable results across different sample sources and instruments
Solution Approach 1:
The patent performs preliminary characterization of matrix effects by infusing multiple candidate internal standards and measuring their response factors across different sample matrices before actual analysis. This preliminary data is stored and used to select the most appropriate internal standard for each analyte, enabling accurate correction even in untargeted mode.
Solution Approach 2:
The patent systematically varies parameters including internal standard concentration, infusion flow rate, and matrix composition to optimize correction performance. By adjusting these parameters and measuring their effects on signal response, the method identifies optimal conditions that maximize correction accuracy across diverse sample types.
3Adaptability or versatility
If post-column infusion of internal standards is implemented, then matrix effect correction is achieved without requiring reference standards, but additional equipment and method complexity are introduced
Solution Approach 1:
The patent designs the post-column infusion system to serve multiple functions: it provides internal standards for quantification, enables matrix effect correction, and allows for quality control through monitoring of internal standard response. This multi-functionality reduces the need for separate systems or procedures.
Solution Approach 2:
The system uses the sample matrix itself to deliver the internal standards through post-column infusion, eliminating the need for separate standard addition steps. The internal standards are automatically introduced and co-elute with analytes, with the system self-regulating through feedback from detected signals.
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 more accurate and precise quantitation of analytes across different samples and instruments, reducing variability and allowing for absolute quantitation of unknown metabolites, even when reference materials are not available, by effectively correcting for matrix effects in LC-MS analysis.
Implementation Method 1
a detection unit comprising a mass spectrometer coupled through an ionization source
Implementation Method 2
Liquid chromatography-mass spectrometry (LC-MS)
Data Source
AI summary
The present invention relates to a method for quantifying one or more analytes in a sample by an analysis system comprising a separation unit (LC column), a means of adding a solution post-column (Connector), and a detection unit comprising a mass spectrometer coupled through an ionization source, the method comprising: ⋅ (i) inducing matrix effect on the analytes in the sample and on the post-column infused internal standards (PCI-ISs); ⋅ (ii) matching one or more post-column infused internal standard (PCI-IS) to each analyte that best matches the analyte's response to the matrix effect, and ⋅ (iii) storing the analyte-matched PCI-IS identification and, optionally, associated response data in a library; and ⋅ (iv) applying the analyte-matched PCI-IS to the analyte in other samples to correct the analyte peak responses for the matrix effect during ionization and to obtain (absolute) quantitation of the analyte using the response data.