Busulfan Amide Derivative for Stable Immunoassay Calibration

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The instability of busulfan standards in immunological assays leads to inaccurate results due to decomposition, complicating the calibration and monitoring of busulfan levels in patient samples during chemotherapy, which is crucial for managing side effects.

Innovation Solution

A stable amide derivative of busulfan, specifically the formula II amide, is developed, which maintains stability and produces results that correlate with known busulfan concentrations, allowing its use as a substitute in immunoassay kits and calibration kits for accurate quantification of busulfan in biological fluids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If busulfan standards are used in immunoassay kits for quantification, then accurate measurement of busulfan levels can be achieved, but the standards decompose over time leading to instability and inaccurate results

Engineering Contradiction:

Improveaccuracy of busulfan quantificationVSAvoidstability of busulfan standards

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent introduces a stable busulfan derivative as an intermediary substance that serves as a surrogate standard in immunoassays. This derivative maintains structural similarity to busulfan, allowing it to be recognized by the same antibodies, but possesses enhanced stability against hydrolysis and decomposition. The derivative acts as a mediator that transfers the quantification function from unstable busulfan standards to stable alternative standards, resolving the contradiction between measurement accuracy and standard stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the chemical parameters of busulfan by replacing the labile methanesulfonate groups with more stable functional groups in the derivative structure. This parameter change preserves the immunoreactive core structure necessary for antibody binding while eliminating the chemically unstable portions that undergo hydrolysis. The modified parameters result in a standard that maintains measurement accuracy through structural similarity while achieving long-term stability through reduced chemical reactivity.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If busulfan standards are stored at room temperature for extended periods, then ease of use is improved, but decomposition occurs leading to loss of substance and measurement errors

Engineering Contradiction:

Improveconvenience of standard storage and useVSAvoiddecomposition of busulfan standards

Core Design Contradiction:

Ease of operationVSLoss of substance

Solution Approach 1:

The patent effectively creates a 'permanent' standard by developing a busulfan derivative that does not require frequent replacement due to decomposition. While the principle typically refers to disposable items, in this context it inverts the approach: instead of using unstable standards that must be frequently replaced (short-living), the patent creates a stable derivative that serves as a long-living, reusable standard. This eliminates the cycle of decomposition and replacement, improving ease of operation while preventing substance loss.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Stability of the object's composition

If frozen storage of busulfan standards is implemented to prevent decomposition, then stability is improved, but complexity and expense of the assay process increase

Engineering Contradiction:

Improvestability of busulfan standardsVSAvoidcomplexity of storage and handling requirements

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent extracts the unstable methanesulfonate groups from the busulfan molecule and replaces them with stable functional groups in the derivative structure. By removing the chemically labile portions that necessitate frozen storage, the patent creates a standard that can be stored under simpler conditions. This extraction of the problematic functional groups eliminates the need for complex frozen storage infrastructure while maintaining stability, thereby reducing device and process complexity.

Inventive Principle:

Principle #2Taking out (Extraction)

4Measurement precision

If multiple calibration standards with different concentrations are prepared, then measurement precision across the detection range is improved, but the amount of substance required for calibration increases

Engineering Contradiction:

Improveaccuracy of quantification across concentration rangeVSAvoidamount of busulfan standard material needed

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent creates a copy of busulfan in the form of a stable derivative that can be synthesized and stored in advance. Multiple concentration levels of this derivative can be prepared as calibration standards without requiring large amounts of unstable native busulfan. The derivative serves as a reproducible copy that can be manufactured in bulk and stored, eliminating the need to continuously prepare fresh standards from limited busulfan stock, thereby reducing the quantity of substance required while maintaining precision across the detection range.

Inventive Principle:

Principle #26Copying

Data Source

PatentUS8329416B2Stabilized standards for busulfan immunoassay

Publication Date: 2012.12.11 SALADAX BIOMEDICAL INC

AI summary

Use of busulfan amide as stabilized standards in immunoassays for quantifying the amount of busulfan in samples of human biological fluids, methods for carrying out said immunoassay and kits for use in said immunoassay.