Method for detecting genotoxic impurities in indobufen bulk drug

A genotoxicity and detection method technology, applied in the direction of measuring devices, material separation, analysis of materials, etc., can solve the problems of difficult detection and low limit, and achieve the effects of high sensitivity, strong specificity, and simple experimental operation

Pending Publication Date: 2022-05-13
HANGZHOU ZHONGMEI HUADONG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its low limit and difficult detection, there is no literature reporting the detection method of genotoxic impurities 2-(4-amino)phenylbutyric acid and 2-(4-nitro)phenylbutyric acid

Method used

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  • Method for detecting genotoxic impurities in indobufen bulk drug
  • Method for detecting genotoxic impurities in indobufen bulk drug
  • Method for detecting genotoxic impurities in indobufen bulk drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1 Separation and determination of genotoxic impurity 2-(4-aminophenyl) butyric acid in indobufen raw materials by liquid chromatography-mass chromatography

[0060] (1) Chromatographic conditions

[0061] Instrument: Agilent 6470 HPLC triple quadrupole mass spectrometer

[0062] Chromatographic column: ACQUITY BEH C18 2.1mm×50mm, 1.7μm

[0063] Mobile phase: Solvent A: 0.01% acetic acid aqueous solution; Solvent B: acetonitrile, eluted according to the following gradient:

[0064]

[0065] Diluent: Acetonitrile-Water (50:50)

[0066] Flow rate: 0.3mL / min

[0067] Column temperature: 35°C

[0068] Injection volume: 5μl

[0069] Mass spectrometry conditions: Electrospray ion source, positive ion scan mode

[0070] The drying gas, atomizing gas and sheath gas are all nitrogen; the collision gas is high-purity nitrogen;

[0071] Drying gas temperature: 300°C

[0072] The drying gas flow rate is: 6L / min

[0073] Atomizing gas pressure: 35psi

[0074] She...

Embodiment 2

[0102] (1) Except for the chromatographic column and elution gradient, other chromatographic conditions are the same as in Example 1. The chromatographic column is ZORBAX SB-C8 3.0×100mm, 1.8 μm, and the elution gradient is:

[0103] time (min) 0.01 1 3 3.1 5 Solvent A(%) 90 90 10 90 90 Solvent B(%) 10 10 90 10 10

[0104] (2) solution preparation and assay method are all with embodiment 1

[0105] (3) Sample injection and result analysis

[0106] Take diluent blank, reference substance solution (concentration is 30% of limit, 1.125ng / mL), standard-added need testing solution sample injection respectively, record chromatogram. Results The peaks of 2-(4-aminophenyl)butyric acid could achieve baseline separation under these conditions, and there was no interference from the blank solution, samples and impurities in the samples; the S / N was 16.9, greater than 10. The specificity and sensitivity of the method can meet the requirements for t...

Embodiment 3

[0115] Example 3 Separation and determination of genotoxic impurity 2-(4-nitrophenyl)butyric acid in indobufen raw materials by liquid chromatography-mass chromatography

[0116] (1) Chromatographic conditions

[0117] Instrument: Agilent 6470 HPLC triple quadrupole mass spectrometer

[0118] Chromatographic column: ACQUITY BEH C18 2.1mm×50mm, 1.7μm

[0119] Mobile phase: solvent A: 20mmol / L ammonium acetate solution; solvent B: acetonitrile, eluted according to the following gradient:

[0120] time (min) 0.01 1 2 4 4.1 5 Solvent A(%) 90 90 10 10 90 90 Solvent B(%) 10 10 90 90 10 10

[0121] Diluent: Methanol

[0122] Flow rate: 0.3mL / min

[0123] Column temperature: 35°C

[0124] Injection volume: 2μl

[0125] Mass spectrometry conditions: Electrospray ion source, negative ion scan mode

[0126] The drying gas, atomizing gas and sheath gas are all nitrogen; the collision gas is high-purity nitrogen;

[0127] Drying gas tempera...

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Abstract

The invention discloses a method for detecting genotoxic impurities in an indobufen bulk drug. According to the method, octadecyl silane bonded silica gel or octyl bonded silica gel is used as a stationary phase for chromatographic separation of genotoxic impurities, a mass spectrum detector is used for analysis and detection, and the genotoxic impurities 2-(4-amino) phenylbutyric acid and / or 2-(4-nitro) phenylbutyric acid can be detected independently or simultaneously. According to the method, the genotoxic impurity 2-(4-amino) phenylbutyric acid and / or 2-(4-nitro) phenylbutyric acid can be independently or simultaneously and effectively separated, the content of the genotoxic impurity can be accurately determined, the specificity is high, the sensitivity is high, and the method has extremely important significance on quality control and safety guarantee of indobufen bulk drugs.

Description

technical field [0001] The invention belongs to the field of pharmaceutical analytical chemistry, and in particular relates to a detection method for the determination of two genotoxic impurities, 2-(4-aminophenyl) butyric acid and 2-(4-nitrophenyl) butyric acid in indobufen crude drug , for the analysis and limit determination of the genotoxic impurities 2-(4-aminophenyl)butyric acid and 2-(4-nitrophenyl)butyric acid in indobufen bulk drug. Background technique [0002] Indobufen (Indobufen) is a derivative of isoindolinyl phenylbutyric acid, an inhibitor of platelet aggregation, which was first listed in Italy in 1984. [0003] Its chemical name is (±)2-[4-(1-oxo-2-isoindolinyl)phenyl]butanoic acid, molecular formula C 18 h 17 NO 3 , the precise molecular weight is 295.12, and the structural formula is as follows: [0004] [0005] Indobufen exerts its anti-platelet aggregation effect mainly through the following mechanisms: (1) Reversible inhibition of platelet cyc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 张霞王新月张璇张志明胡方剑倪振华谢小燕陈磊独文娜谭芳赵澄
Owner HANGZHOU ZHONGMEI HUADONG PHARMA
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