3-Methyl-1-Phenyl-2-Pyrazolin-5-One HPLC for Phenylhydrazine Detection

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Solution Overview

Problem

Existing methods for analyzing phenylhydrazine in 3-methyl-1-phenyl-2-pyrazolin-5-one bulk drugs are not accurate and simple, and there is a need for a method to treat and produce drugs with controlled phenylhydrazine content to manage amyotrophic lateral sclerosis (ALS) effectively.

Innovation Solution

A method involving the use of specific acidic waters and water-soluble organic solvents to measure phenylhydrazine content accurately, ensuring it is 20 ppm or less, and producing drugs with controlled phenylhydrazine content using high-performance liquid chromatography (HPLC) analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional HPLC methods with ammonium dihydrogen phosphate solution are used to analyze phenylhydrazine, then the analysis can be performed, but the measurement precision and simplicity are insufficient

Engineering Contradiction:
Improvephenylhydrazine content measurement accuracyVSAvoidanalysis method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the chemical parameters of the dissolution liquid by specifying precise pH values (pH 2.0-3.5) and composition ratios (ammonium dihydrogen phosphate to methanol at 95:5 to 50:50 v/v). These parameter optimizations enable accurate phenylhydrazine measurement while maintaining method simplicity, directly resolving the contradiction between measurement precision and device complexity.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If phenylhydrazine content is not strictly controlled, then drug production is simpler, but the therapeutic effectiveness and safety for ALS treatment are compromised

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidphenylhydrazine content control
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent implements a feedback mechanism by establishing a specified phenylhydrazine content range (0.01-10 μg/mL) and requiring verification through standardized HPLC analysis. This feedback loop ensures that phenylhydrazine content is strictly controlled within therapeutic limits, guaranteeing both therapeutic effectiveness and manufacturing precision for ALS treatment drugs.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If complex dissolution liquids are used to ensure complete phenylhydrazine dissolution, then measurement accuracy improves, but the ease of operation decreases

Engineering Contradiction:
Improvephenylhydrazine detection accuracyVSAvoidsample preparation simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent optimizes the dissolution liquid parameters by defining specific pH ranges (2.0-3.5) and composition ratios (ammonium dihydrogen phosphate to methanol at 95:5 to 50:50 v/v). These standardized parameter changes enable complete phenylhydrazine dissolution and accurate measurement while maintaining ease of operation through clear preparation guidelines, resolving the contradiction between measurement precision and ease of operation.

Inventive Principle:
Principle #35Parameter changes

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 and simple phenylhydrazine measurement, allowing effective treatment and production of 3-methyl-1-phenyl-2-pyrazolin-5-one drugs with controlled phenylhydrazine content for ALS management.

Implementation Method 1

analyzing phenylhydrazine by HPLC using the liquid for dissolution of ammonium dihydrogen phosphate solution-methanol whose pH is adjusted to 3.5 with phosphoric acid as a mobile phase

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP3761027B1Analysis method of 3-methyl-1-phenyl-2-pyrazolin-5-one bulk drug
Publication Date: 2025.10.29 TANABE PHARMA CORP
  • EP3761027B1 patent drawingFigure 1~2
  • EP3761027B1 patent drawingFigure 3~4
  • EP3761027B1 patent drawingFigure 5~6

AI summary

This method of analyzing the phenylhydrazine content in a 3-methyl-1-phenyl-2-pyrazolin-5-one bulk drug involves: obtaining a first measured value by measuring the phenylhydrazine content of a standard solution that contains phenylhydrazine or a salt thereof, a first acidic water and a first water-soluble organic solvent, and that exhibits a phenylhydrazine concentration of 0.01 pg/mL to 10 pg/mL; obtaining a second measured value by measuring the phenylhydrazine content in a sample solution that contains a 3-methyl-1-phenyl-2-pyrazolin-5-one bulk drug, a second acidic water and a second water-soluble organic solvent; and detecting the phenylhydrazine content in the 3-methyl-1-phenyl-2-pyrazolin-5-one bulk drug on the basis of the first measured value and the second measured value. The first acidic water is at least one type selected from hydrochloric acid, an aqueous acetic acid solution, and the like, the first water-soluble organic solvent is at least one type selected from acetonitrile and methanol, the second acidic water is at least one type selected from hydrochloric acid, an aqueous acetic acid solution, and the like, and the second water-soluble organic solvent is at least one type selected from acetonitrile, and methanol.