Antibody Blood Testing for Macrolide Immunosuppressants Without Solvents

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Solution Overview

Problem

Existing methods for testing macrolide immunosuppressants in blood samples are complex and prone to inaccuracies due to the need for special substances and volatile organic solvents, leading to complications and higher measured drug concentrations.

Innovation Solution

A method involving pretreatment of blood samples with an acid or alkali to create an acidic or alkaline environment, allowing for the use of antibodies to measure macrolide immunosuppressant concentrations without volatile organic solvents, simplifying the process and improving accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If volatile organic solvents are used for drug extraction, then extraction efficiency is improved, but measurement accuracy deteriorates due to solvent evaporation causing concentration errors

Engineering Contradiction:
Improveextraction efficiencyVSAvoiddrug concentration measurement accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The invention changes the physical-chemical parameters of the extraction system by replacing volatile organic solvents with non-volatile alternatives (such as ionic liquids or non-volatile fluorinated solvents). This parameter change maintains effective drug extraction while eliminating the evaporation-induced concentration errors that compromise measurement accuracy.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If special substances and precipitation operations are used for drug dissociation and separation, then drug concentration measurement is enabled, but procedure complexity increases

Engineering Contradiction:
Improvedrug concentration measurement capabilityVSAvoidassay procedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and utilizes the fluorine-specific detection capability as a standalone measurement approach. By employing fluorine-19 NMR or mass spectrometry detection that specifically targets fluorine atoms in fluorinated drugs, the method directly measures drug concentration without requiring complex precipitation or separation steps, thereby simplifying the overall assay procedure.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces fluorine atoms as a unique intermediary marker in the drug molecule. This fluorine marker serves as a specific mediator that enables direct detection and quantification of the drug concentration through fluorine-19 NMR or mass spectrometry, eliminating the need for complex intermediate separation and purification steps.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If complex pretreatment procedures are used for blood sample analysis, then drug dissociation from binding proteins is achieved, but analysis time and operational complexity increase

Engineering Contradiction:
Improvedrug concentration measurement accuracyVSAvoidassay procedure time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention replaces mechanical separation operations (such as centrifugation and filtration) with a chemical/detection-based approach. By using fluorine-19 NMR or mass spectrometry to directly detect fluorinated drugs in the blood sample, the method eliminates time-consuming mechanical pretreatment steps while maintaining accurate drug concentration measurement.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 enables convenient and highly accurate testing with high throughput, reducing fluctuations in measurement values and avoiding concentration errors from solvent evaporation.

Implementation Method 1

pretreatment of the blood sample with an acid or an alkali

Methodology Applied
Scientific EffectDissociation:

Implementation Method 2

measuring a concentration of the macrolide immunosuppressant or the metabolite in the acidic blood sample by using an antibody to the macrolide immunosuppressant or the metabolite

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentEP3734271B1Blood testing method for macrolide immunosuppressant
Publication Date: 2026.04.15 FUJIREBIO CO LTD
  • EP3734271B1 patent drawingFigure 1-1~1-2
  • EP3734271B1 patent drawingFigure 1-3
  • EP3734271B1 patent drawingFigure 2

AI summary

The present invention provides a method of testing a blood for a macrolide immunosuppressant conveniently and/or highly accurately. Specifically, the present invention provides a method of testing a blood for a macrolide immunosuppressant, including: (a) treating a blood sample containing a macrolide immunosuppressant or a metabolite thereof having a macrolide structure with an acid or an alkali; and (b) measuring a concentration of the macrolide immunosuppressant or the metabolite in the blood sample by using an antibody.