Whole-Blood Immunosuppressant Quantification Through Hematocrit Conversion

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Solution Overview

Problem

Existing methods for therapeutic drug monitoring (TDM) of immunosuppressants like mycophenolic acid in organ transplant patients face challenges due to the need for simultaneous analysis in both plasma and whole blood fractions, which is difficult to achieve with minimally invasive home sampling, especially when separating plasma fractions is challenging and blood volumes are small.

Innovation Solution

A method that converts the concentration of mycophenolic acid in a whole blood fraction to a plasma fraction using the hematocrit value, allowing for quantitative analysis without separating the blood sample, utilizing liquid chromatography mass spectrometry (LC-MS) for accurate measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If plasma fraction separation is performed for mycophenolic acid measurement, then measurement precision is improved, but device complexity and operation difficulty increase due to the need for separation equipment and procedures

Engineering Contradiction:
Improvemycophenolic acid concentration measurement precisionVSAvoidblood sample separation equipment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the plasma separation step from the measurement process by using hematocrit-based calculation to estimate plasma concentration from whole blood measurements, thereby removing the need for actual plasma separation equipment and procedures while maintaining measurement precision

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces hematocrit value as an intermediary parameter that mediates between whole blood measurement and plasma concentration estimation, allowing accurate conversion without physical separation of plasma from whole blood

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If frequent blood sampling is performed for TDM, then measurement precision is improved, but loss of time and patient inconvenience increase

Engineering Contradiction:
Improvetherapeutic drug monitoring precisionVSAvoidtime loss due to frequent blood sampling
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent changes the measurement parameter from plasma fraction to whole blood fraction, which can be obtained from minimally invasive home sampling, thereby reducing the frequency of blood draws while maintaining monitoring precision through hematocrit-based concentration conversion

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If minimally invasive home blood sampling is implemented, then ease of operation is improved, but the amount of blood collected decreases

Engineering Contradiction:
Improvehome blood sampling convenienceVSAvoidblood sample volume
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent changes the approach from requiring plasma separation (which needs larger blood volumes) to using whole blood directly, allowing accurate measurement even from small home-collected blood samples through hematocrit-based concentration estimation

Inventive Principle:
Principle #35Parameter changes

4Productivity

If simultaneous analysis of multiple immunosuppressants is performed, then productivity is improved, but device complexity increases due to multiple measurement requirements

Engineering Contradiction:
Improvesimultaneous analysis capabilityVSAvoidmulti-analyte measurement system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent creates a universal measurement approach using whole blood fraction that can simultaneously measure multiple immunosuppressants (mycophenolic acid, tacrolimus, cyclosporine A, everolimus) with different measurement principles, eliminating the need for separate plasma separation and multiple specialized measurement systems

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

Enables accurate quantification of mycophenolic acid and other immunosuppressants in whole blood samples, facilitating minimally invasive home sampling and reducing the need for frequent blood draws, while maintaining analytical precision.

Implementation Method 1

utilizing liquid chromatography mass spectrometry (LC-MS) for accurate measurement

Methodology Applied
Scientific EffectLiquid chromatography mass spectrometry:

Data Source

PatentEP4628891A1Method for quantifying analyte containing mycophenolic acid and one or more other immunosuppressants in target blood sample
Publication Date: 2025.10.08 SHIMADZU CORP
  • EP4628891A1 patent drawingFigure 1
  • EP4628891A1 patent drawingFigure 2A~2B
  • EP4628891A1 patent drawingFigure 3A~3C

AI summary

The present invention provides a means for quantitatively analyzing an analyte comprising mycophenolic acid and one or more other immunosuppressants, using a whole blood fraction, without separating a blood sample. One aspect of the present invention relates to a method for quantifying an analyte comprising mycophenolic acid and one or more other immunosuppressants in a blood sample of a subject, wherein the method comprises: an analyte concentration-measuring step of measuring a concentration of the analyte comprising mycophenolic acid and one or more other immunosuppressants in a whole blood fraction of the blood sample; a hematocrit value-obtaining step of obtaining a hematocrit value of the blood sample of the subject; and a mycophenolic acid concentration-converting step of converting the concentration of mycophenolic acid in the whole blood fraction of the blood sample to a concentration of mycophenolic acid in a plasma fraction of the blood sample, based on the hematocrit value.