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Liquid chromatography-mass spectrometry detection method for potential genotoxic impurities in irbesartan

An impurity, mass spectrometry technology, applied in instruments, measuring devices, scientific instruments, etc., can solve the problem that the detection sensitivity cannot meet the requirements and has not yet been found.

Pending Publication Date: 2021-05-07
ZHEJIANG TIANYU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Since the acceptable limit of impurity 1 in the irbesartan bulk drug is only 5.0ppm, the detection sensitivity of the conventional high-performance liquid chromatography (HPLC) test method cannot meet the requirements, and it can detect sensitively and accurately in the irbesartan bulk drug. Trace amounts of impurity 1 are technically difficult
In the prior art, there is no report on the inspection method of impurity 1 that can achieve a detection limit lower than 5.0ppm

Method used

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  • Liquid chromatography-mass spectrometry detection method for potential genotoxic impurities in irbesartan
  • Liquid chromatography-mass spectrometry detection method for potential genotoxic impurities in irbesartan
  • Liquid chromatography-mass spectrometry detection method for potential genotoxic impurities in irbesartan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Embodiment 1 specificity verification

[0095] 1.1 Diluent (acetonitrile-water (80:20)): Measure 200ml of ultrapure water in 800ml of acetonitrile and mix well;

[0096] 1.2 Impurity 1 stock solution:

[0097] Take 30.55mg of impurity 1 working reference substance, put it in a 100ml volumetric flask, dissolve it with diluent and dilute to the mark, and shake well. Accurately measure 5ml of the above solution, place it in a 100ml volumetric flask, dilute to the mark with diluent, and shake well. Then accurately measure 1ml of the above solution, place it in a 100ml volumetric flask, dilute to the mark with diluent, shake well, and use it as the impurity 1 stock solution, the concentration of impurity 1 in the solution is 152.75ng / ml.

[0098] 1.3 Reference substance solution:

[0099] Accurately measure 1ml of the stock solution of impurity 1 prepared in step 1.2 of this example into a 10ml volumetric flask, dilute to the mark with diluent, and shake well to obtain th...

Embodiment 2

[0115] Example 2 Quantitative limit and detection limit verification

[0116] 2.1 Diluent (acetonitrile-water (80:20)): Measure 200ml of ultrapure water in 800ml of acetonitrile and mix well;

[0117] 2.2 Reference substance solution:

[0118] Precisely measure 1ml of the impurity 1 stock solution prepared in step 1.2 in the specificity verification of Example 1 in a 10ml volumetric flask, dilute to the mark with diluent, shake well, and obtain the reference substance solution. The concentration of impurity 1 in the solution is 15.2750 ng / ml.

[0119] 2.3 Quantitation limit test solution:

[0120] Measure 0.8ml of the reference substance solution prepared in step 2.2 of this embodiment in a 10ml volumetric flask, dilute to the mark with a diluent, and shake up to obtain the limit of quantitation test solution. The concentration of impurity 1 in the solution is 1.2220ng / ml.

[0121] 2.4 Detection limit test solution:

[0122] Measure 3.3ml of the limit of quantitation test ...

Embodiment 3

[0137] Example 3 Linearity and Range Verification

[0138] 3.1 Diluent (acetonitrile-water (80:20)): Measure 200ml of ultrapure water in 800ml of acetonitrile and mix well;

[0139] 3.2 Reference substance solution:

[0140] Precisely measure 1ml of the impurity 1 stock solution prepared in step 1.2 in the specificity verification of Example 1 in a 10ml volumetric flask, dilute to the mark with diluent, shake well, and obtain the reference substance solution. The concentration of impurity 1 in the solution is 15.2750 ng / ml.

[0141] 3.3 Sensitivity solution:

[0142] Measure 0.8ml of the reference substance solution prepared in step 3.2 of this example into a 10ml volumetric flask, dilute to the mark with diluent, shake well, and obtain the sensitivity solution. The concentration of impurity 1 in the solution is 1.2220ng / ml.

[0143] 3.4 Linearity test solution

[0144] Linearity test solution 1: Measure 0.8ml of the reference solution prepared in step 3.2 of this example ...

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Abstract

The invention relates to an LCMS detection method for potential genotoxic impurities in irbesartan. The method comprises the following steps: injecting a blank solution, a reference solution and a test solution into a liquid chromatograph-mass spectrometer, and recording a chromatogram. The LCMS detection method for the potential genotoxic impurities in the irbesartan, provided by the invention, is implemented through a high performance liquid chromatography-mass spectrometry method, and can be used for sensitively and accurately detecting the potential genotoxic impurities in the irbesartan; and the system specificity, the detection limit and the quantitation limit, the linearity and the range, the solution stability, the precision, the accuracy and the durability are verified by referring to the related content of the Chinese pharmacopoeia, and all the aspects meet the requirements.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a liquid chromatography-mass spectrometry (LCMS) detection method for potential genotoxic impurities in irbesartan. Background technique [0002] Irbesartan chemical name: 3-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2- Butyl-1,3-diazaspiro[4,4]non-1-en-4-one was developed by Sanofi and first launched in the UK in 1997. The drug is a class of non-peptide angiotensin II receptor antagonist with good blood pressure lowering effect. Structure is as shown in formula I: [0003] [0004] A trace amount of an azide genotoxic impurity inevitably remains in the irbesartan API produced by the existing process: 5-(4'-(azidomethyl)[1,1'-biphenyl]- 2-yl)-1H-tetrazolium (CAS accession number: 152708-24-2), the chemical structure of which is shown below, and is referred to as Impurity 1 hereinafter. [0005] [0006] The above-mentioned impurity 1 was evaluated by DEREK a...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06G01N30/30G01N30/32G01N30/34G01N30/72
CPCG01N30/02G01N30/06G01N30/30G01N30/32G01N30/34G01N30/72G01N2030/324
Inventor 占新翠胡淑君胡纯洪应燕飞章丹枫王臻朱国荣屠勇军
Owner ZHEJIANG TIANYU PHARMA
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