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Method for detecting genetic toxic impurities of Adenafil citrate

A genotoxic and citric acid technology, which is applied in the field of detection of genotoxic impurities of idenafil citrate, can solve the problems of inability to control quality, low sensitivity, etc., and achieve detection sensitivity and accuracy improvement, detection Improved sensitivity and high reproducibility

Pending Publication Date: 2022-02-18
BEIJING YUEKANGKECHUANG PHARM TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the conventional liquid phase method is used to detect impurity A, the general detection limit is about 30ppm, the sensitivity is low, and the quality control requirements cannot be met.

Method used

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  • Method for detecting genetic toxic impurities of Adenafil citrate
  • Method for detecting genetic toxic impurities of Adenafil citrate
  • Method for detecting genetic toxic impurities of Adenafil citrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0093] Embodiment 1 specificity test

[0094] Blank solvent: 60% aqueous methanol;

[0095] Preparation of the test sample: take an appropriate amount of edenafil, weigh it accurately, dissolve it with dimethyl sulfoxide to a 0.1g / mL stock solution, and then dilute it with a diluent to a 2mg / mL solution;

[0096] Preparation of control solution: Take an appropriate amount of impurity A reference substance, dissolve it in methanol to make a 1mg / mL reference substance stock solution, and then dilute it to make 100μg / mL reference substance stock solution 1 and 10μg / mL reference substance stock solution 2.

[0097] Preparation of control solution: Take reference substance stock solution 1 and reference substance stock solution 2 to make a 10 μg / mL reference substance solution. Then take the reference substance solution and the 0.1g / mL test solution and dilute with the diluent to make a 1.00ng / mL solution respectively.

[0098] Preparation of system suitability solution: Take ref...

Embodiment 2

[0105] Embodiment 2 linearity and range test

[0106] Diluent: 60% methanol water solution.

[0107] Preparation of the test sample: take an appropriate amount of edenafil, accurately weigh it, and dissolve it with dimethyl sulfoxide to form a 0.1g / mL stock solution;

[0108] Preparation of control solution: Take an appropriate amount of impurity A reference substance, dissolve it in methanol to make a 1mg / mL reference substance stock solution, and then dilute it to make 100μg / mL reference substance stock solution 1 and 10μg / mL reference substance stock solution 2.

[0109] Preparation of linear solution of reference substance: Take reference substance stock solution 1 and reference substance stock solution 2 to make 1μg / mL, 2μg / mL, 5μg / mL, 10μg / mL, 25μg / mL, 50μg / mL, 80μg / mL, 100μg / mL and a series of linear reference solutions. Then take a series of linear reference solution and 0.1g / mL test solution and dilute with diluent to make 1ng / mL, 2ng / mL, 5ng / mL, 10ng / mL, 25ng / mL, ...

Embodiment 3

[0114] Embodiment 3 detection limit, quantitative limit

[0115] Take an appropriate amount of the impurity A reference substance, prepare it into a reference substance solution, and prepare it into a test solution through step-by-step dilution. When the three-fold noise value S / N ≥ 3, it is used as the detection limit; when S / N ≥ 10, as the limit of quantitation. The results are shown in the table below.

[0116] Table 4 Detection limit results

[0117]

[0118] Table 5 Quantitation limit results

[0119]

[0120] Conclusion: The detection limit of genotoxic impurities in this product is 0.40ng / mL, which is equivalent to 0.2ppm of the test solution; the quantification limit is 1.00ng / mL, which is equivalent to 0.5ppm of the test solution. The precision RSD of 6-needle injection for quantitative concentration determination was 5.40%. It meets the sensitivity requirements for the determination of genotoxic impurities of this product.

[0121] Embodiment 3 recovery te...

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Abstract

The invention provides a method for detecting genetic toxic impurities of SM3 (4-amino-1-methyl-3-n-propylpyrazole-5-formamide) in a class 1 new drug aldenafil citrate bulk drug. A sample to be detected is detected by using a high performance liquid chromatography-mass spectrometry tandem method. According to the method provided by the invention, the genotoxic impurity 4-amino-1-methyl-3-n-propylpyrazole-5-formamide in the Adenafil can be effectively determined with ultrahigh sensitivity, so that strict quality control is implemented.

Description

technical field [0001] The application relates to the field of drug detection, and relates to a method for detecting genotoxic impurities of edenafil citrate. Background technique [0002] Aildenafil citrate, chemical name: 1-[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4 ,3-d]pyrimidin-5-yl)-4-ethoxybenzenesulfonyl]-cis-3,5-dimethylpiperazine citrate (C 23 h 32 N 6 o 4 S·C 6 h 8 o 7 ). Aldenafil citrate is a novel derivative of sildenafil citrate, which is a type 5 phosphodiesterase (Phosphodiesterase 5, PDE5) inhibitor, used for the treatment of male erectile dysfunction (ED). Aldenafil citrate is a new class 1 drug for treating ED patients. It is similar in structure to sildenafil and has better curative effect. [0003] Aldenafil citrate genotoxic impurity Impurity A is a genotoxic impurity, which has the risk of teratogenic and carcinogenic, and requires accurate quantitative methods to control the quality of the drug. At present, the conventional liqui...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06G01N30/34G01N30/36G01N30/72
CPCG01N30/02G01N30/06G01N30/34G01N30/36G01N30/7266
Inventor 宋更申李中伟王云锦李娇
Owner BEIJING YUEKANGKECHUANG PHARM TECH CO LTD
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