LC-MS Measurement Quality Checks With Dynamic Internal Standard Limits
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Solution Overview
Problem
Existing LC-MS quality assurance methods rely on internal standards (IStd) that can lead to high false sample flagging rates due to broad acceptance ranges or require manual chromatogram review, reducing the effectiveness of quality monitoring.
Innovation Solution
A computer-implemented method using a monitoring parameter to automatically flag LC-MS measurements based on the ratio of analyte and internal standard signals, reducing false positives and negatives without manual review.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad acceptance ranges are used for internal standard parameters, then the false sample flagging rate decreases, but the power of internal standard monitoring decreases with risk of overlooking bad measurements
Solution Approach 1:
The patent changes the parameter from fixed acceptance ranges to dynamic monitoring parameters calculated from the relationship between internal standard signal and analyte signal. This allows the acceptance criteria to adapt to each specific measurement context, resolving the contradiction between reducing false positives and maintaining detection power.
Solution Approach 2:
The patent introduces dynamic monitoring parameters that are calculated based on the actual signal relationship between internal standard and analyte. Instead of static acceptance ranges, the system continuously adjusts quality criteria based on measured signals, enabling both reduced false flagging and maintained monitoring power.
2Measurement precision
If strict acceptance ranges are used for internal standard parameters, then the power of quality monitoring increases, but the false sample flagging rate increases requiring manual review
Solution Approach 1:
The patent transforms fixed strict acceptance ranges into dynamic monitoring parameters that adapt to each measurement. This reduces unnecessary manual reviews while maintaining quality monitoring power by adjusting criteria based on actual signal relationships.
Solution Approach 2:
The system performs self-evaluation by automatically calculating monitoring parameters and comparing them against quality criteria, reducing the need for expert manual review. The system serves itself by using its own measured signals to determine quality acceptance.
3Measurement precision
If manual chromatogram review is performed for verification, then the accuracy of quality assessment increases, but the time and workload increase
Solution Approach 1:
The system performs automatic quality assessment by calculating monitoring parameters from measured signals and comparing them against quality criteria. This self-service approach maintains accuracy while eliminating time-consuming manual review.
Solution Approach 2:
The patent replaces manual expert review (mechanical human process) with automated computational evaluation of monitoring parameters. The system uses algorithmic comparison of signal relationships to assess quality, substituting human analysis with automated processing.
Data Source
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AI summary
A method for quality check of at least one Liquid Chromatography-Mass Spectrometry (LC-MS) measurement on a sample comprising an analyte of interest and a defined amount of at least one internal standard is proposed. The method comprises the following steps a) (120) determining an information (peakAreaaqn) about an analyte signal and an information (peakAreatqn) about an internal standard signal of the LC-MS measurement; b) (122) determining at least one monitoring parameter by using the information about the analyte signal and the information about the internal standard signal by using at least one processing device (114), wherein the monitoring parameter comprises a minimal limit for the internal standard signal for said analyte signal of said sample; c) (124) comparing the information about the internal standard signal to the monitoring parameter by using the processing device (114), wherein the LC-MS measurement is flagged by using the processing device (114) as to fulfil the quality check in case the information about the internal standard signal is greater or equal to the monitoring parameter or otherwise as failed.