Non-polar Analyte Detection via Selective Extraction and LC-MS/MS

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current analytical methods for detecting non-polar pesticide residues like acequinocyl in plant-derived samples, such as cannabis, face challenges with high matrix interferences and poor reproducibility due to the removal of non-polar analytes during the clean-up process, leading to insufficient sensitivity and increased costs for achieving regulatory limits.

Innovation Solution

A method utilizing liquid-liquid extraction (LLE) or solid-phase extraction (SPE) to enrich and isolate non-polar analytes, followed by liquid chromatography and tandem mass spectrometry (LC-MS/MS) with a mobile phase containing ammonium acetate, allowing for detection limits of 50 ppb or less, and a kit for detecting non-polar analytes with reagents for sample purification and analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If Quechers method with clean-up step is used to remove non-polar contaminants, then matrix interferences are reduced, but non-polar analytes are also removed leading to poor sensitivity

Engineering Contradiction:
Improvematrix interferencesVSAvoiddetection sensitivity
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent extracts and removes only the polar contaminants from the sample matrix while preserving the non-polar analytes. This is achieved by using a polar clean-up phase (such as silica or C18) that selectively retains polar substances, allowing non-polar analytes to pass through or be eluted separately, thus eliminating matrix interferences without losing the target non-polar compounds

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent modifies the clean-up process to create different local properties within the extraction system. By using phases with specific polarities (polar for clean-up, non-polar for analyte recovery), the system achieves selective interaction where polar contaminants are removed at one stage while non-polar analytes are preserved and recovered at another stage

Inventive Principle:
Principle #3Local quality

2Adaptability or versatility

If standard Quechers method is used for non-polar analytes, then general pesticide detection is achieved, but detection limits are insufficient for low regulatory limits

Engineering Contradiction:
Improvemethod applicabilityVSAvoiddetection limit
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent changes the polarity parameter of the clean-up phase to match the analyte characteristics. By using a polar clean-up phase instead of a non-polar one, the method achieves selective retention of polar contaminants while allowing non-polar analytes to pass through, thereby improving detection limits for non-polar substances without sacrificing method versatility

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If increased sample amount is used to achieve required sensitivity, then detection sensitivity is improved, but analysis cost increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidanalysis cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent extracts and removes the problematic non-polar contaminants that cause matrix interferences and signal suppression. By eliminating these interferents through selective extraction, the method achieves high sensitivity for non-polar analytes using standard sample amounts, thereby avoiding the need to increase sample quantity and the associated costs

Inventive Principle:
Principle #2Taking out (Extraction)

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

The method achieves highly sensitive detection and quantification of non-polar analytes at or below regulatory limits, reducing costs and improving reproducibility by using LLE or SPE for clean-up and LC-MS/MS analysis with ammonium acetate facilitating robust peak detection.

Implementation Method 1

a non-polar phase; purifying the first solution in a second purification step to obtain a second solution comprising the non-polar analyte

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 2

a non-polar phase; purifying the first solution in a second purification step to obtain a second solution comprising the non-polar analyte

Methodology Applied
Scientific EffectSolid-phase extraction: Adsorption

Implementation Method 3

subjecting the second solution to an analysis by liquid chromatography (LC) followed by mass spectrometry (MS)

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP3168615B2Methods for detecting non-polar analytes with high sensitivity
Publication Date: 2021.10.20 WATERS TECHNOLOGY CORP
  • EP3168615B2 patent drawingFigure 1
  • EP3168615B2 patent drawingFigure 2
  • EP3168615B2 patent drawingFigure 3

AI summary

The technology of the present application is directed to methods and kits for detecting and quantifying a non-polar analyte in a plant-derived sample. The technology uses a simple extraction, e.g., a liquid-liquid extraction (LLE) or solid-phase extraction (SPE), to enrich a sample for a non-polar analyte of interest and to remove contaminants. After the extraction and clean-up steps, liquid chromatography and mass spectrometry are used to detect the non-polar analyte. In one embodiment, acequinocyl and/or its derivatives is analyzed using liquid chromatography and tandem mass spectrometry (LC-MS/MS) and the improved LC-MS/MS conditions allows detection limits of acequinocyl and/or its derivatives of 50 ppb or less.