LC-MS/MS Steroid Panel Assay for Single-Injection CAH Testing

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Solution Overview

Problem

Current methods for detecting congenital adrenal hyperplasia (CAH) analytes are limited in their ability to accurately measure multiple analytes simultaneously in a single sample injection, which is essential for effective diagnosis and monitoring.

Innovation Solution

The use of tandem mass spectrometry to detect and quantify multiple CAH panel analytes, including pregnenolone, 17-OH pregnenolone, progesterone, 17-OH progesterone, DHEA, androstenedione, testosterone, deoxycorticosterone, 11-deoxycortisol, cortisone, corticosterone, dihydrotestosterone, and cortisol, in a single sample injection, allowing for simultaneous measurement and improved diagnostic accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If current detection methods are used for CAH analytes, then the diagnostic process can be performed, but multiple analytes cannot be measured simultaneously in a single sample injection

Engineering Contradiction:

Improvethroughput of analyte detectionVSAvoidaccuracy of multiple analyte measurement

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent combines multiple analyte detection capabilities into a single mass spectrometry system configuration, allowing simultaneous measurement of multiple CAH panel analytes (including 17-OH progesterone, progesterone, testosterone, DHEA, androstenedione, cortisol, and other steroid hormones) in one sample injection rather than requiring separate detection processes for each analyte

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The mass spectrometry system is configured with universal detection capabilities that can measure multiple different types of steroid hormone analytes simultaneously, making the system multi-functional for comprehensive CAH diagnosis and monitoring in a single analytical run

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Productivity

If multiple analytes are detected in a single sample injection, then diagnostic efficiency is improved, but the device complexity increases

Engineering Contradiction:

Improvediagnostic efficiencyVSAvoidcomplexity of mass spectrometry system

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent employs an intermediary liquid chromatography separation system that precedes the mass spectrometry detection, using chromatographic separation as a mediator to resolve and deliver multiple analytes to the detector in sequence, thereby managing the complexity of simultaneous multi-analyte detection through staged separation and detection

Inventive Principle:

Principle #24Intermediary (Mediator)

3Measurement precision

If tandem mass spectrometry is used to detect multiple CAH analytes, then measurement accuracy is improved, but the time required for analysis increases

Engineering Contradiction:

Improveaccuracy of analyte quantificationVSAvoidanalysis time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent implements continuous analysis by coupling liquid chromatography separation with tandem mass spectrometry detection in an uninterrupted flow system, where analytes are continuously separated and detected without intermediate handling steps, maintaining continuous useful action throughout the analytical process to minimize time loss while preserving measurement precision

Inventive Principle:

Principle #20Continuity of useful action

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 enables the simultaneous detection of multiple CAH panel analytes in a single sample injection, enhancing diagnostic accuracy and efficiency in monitoring congenital adrenal hyperplasia.

Implementation Method 1

subjecting a sample to an ionization source under conditions suitable to produce one or more ions detectable by mass spectrometry

Methodology Applied

Scientific EffectIonization: Ionisation

Implementation Method 2

determining the amounts of one or more ions from each of the one or more analytes by tandem mass spectrometry

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS20250147053A1Mass spectrometry assay for congenital adrenal hyperplasia

Publication Date: 2025.05.08 QUEST DIAGNOSTICS INVESTMENTS INC

AI summary

A method for determining the amount of a panel of analytes in a sample by mass spectrometry includes purifying the sample by liquid chromatography; ionizing the sample under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes comprising dehydroepiandrosterone (DHEA), cortisol, and androstenedione; determining by tandem mass spectrometry the amount of the one or more ions from each of the analytes; and using the determined amount of the one or more ions to determine the amount of each of the analytes in the sample.