Non-targeted screening method for alkylated genotoxic impurities

An alkylation and gene-like technology, which is applied in instruments, measuring devices, scientific instruments, etc., can solve the problems of poor temperature resistance and difficulty in direct detection of alkylated genotoxic impurities, and achieve good stability and specificity.

Pending Publication Date: 2022-07-01
SHANDONG INST FOR FOOD & DRUG CONTROL
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Problems solved by technology

[0005] In view of the above problems, the present invention proposes a non-targeted screening method for alkylated genotoxic impurities. This method can not only realize the screening of unknown alkylated genotoxic impurities, but also generate derivative products with good stability, which solves the problem of Solved the problem of poor temperature resistance of alkylated genotoxic impurities and difficulty in direct detection

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  • Non-targeted screening method for alkylated genotoxic impurities
  • Non-targeted screening method for alkylated genotoxic impurities
  • Non-targeted screening method for alkylated genotoxic impurities

Examples

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no. 1 example

[0026] A non-targeted screening method for alkylated genotoxic impurities, refer to Reaction Scheme 1, including:

[0027] (1) select 3-amino-N-(4-methoxyphenyl) propionamide as derivatization reagent, get about 100mg of derivatization reagent and place it in the volumetric flask of 10ml, respectively use acetonitrile, DMSO, water, DMF as The solvent dissolves the derivatization reagent and dilutes it to the scale to obtain four different concentration of 10mg / ml derivatization reagent solutions, wherein, the derivatization reagent solutions obtained by using the acetonitrile, DMSO, water, and DMF as solvents are named A1 and A2 respectively. , A3, A4, spare.

[0028] (2) get methyl methanesulfonate 10mg and be placed in the volumetric flask of 10ml, dissolve methyl methanesulfonate respectively with acetonitrile, DMSO, water, DMF as solvent and be diluted to scale, above-mentioned solution gradient dilution is obtained 10 μ g / ml of alkylating reagent solution to obtain four...

no. 2 example

[0036] A non-targeted screening method for alkylated genotoxic impurities, comprising the following steps:

[0037] (1) select 3-amino-N-(4-methoxyphenyl) propionamide as derivatization reagent, get about 100mg of derivatization reagent and place it in the volumetric flask of 10ml, add acetonitrile as solvent to dissolve described derivatization reagent and Dilute to the mark to obtain a derivatization reagent solution with a concentration of 10 mg / ml, which is ready for use.

[0038] (2) Take 10 mg of methyl methanesulfonate and place it in a measuring flask with a volume of 10 ml, dissolve and dilute to the mark with acetonitrile as a solvent, and dilute the above solution gradiently to obtain a 10 μg / ml alkylating reagent solution, which is for subsequent use.

[0039](3) Measure 1 ml of the derivatization reagent solution prepared in step (1), add 1 ml of the alkylating reagent solution prepared in step (2), and mix well to obtain a mixed solution. , 60°C, and 80°C for 1 ...

no. 3 example

[0044] A non-targeted screening method for alkylated genotoxic impurities, comprising the following steps:

[0045] (1) select 3-amino-N-(4-methoxyphenyl) propionamide as derivatization reagent, get about 100mg of derivatization reagent and place it in the volumetric flask of 10ml, add acetonitrile as solvent to dissolve described derivatization reagent and Dilute to the mark to obtain a derivatization reagent solution with a concentration of 10 mg / ml, which is ready for use.

[0046] (2) Take 10 mg of methyl methanesulfonate and place it in a measuring flask with a volume of 10 ml, dissolve and dilute to the mark with acetonitrile as a solvent, and dilute the above solution gradiently to obtain a 10 μg / ml alkylating reagent solution for subsequent use.

[0047] (3) Measure 1 ml of the derivatization reagent solution prepared in step (1), add 1 ml of the alkylating reagent solution prepared in step (2) and mix well, and then heat at 40°C for 1 h. After the reaction is complete...

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Abstract

The invention discloses a non-targeted screening method for alkylated genotoxic impurities, which comprises the following steps: (1) taking an amino compound as a derivative agent, carrying out alkylation reaction on the amino compound and the alkylated genotoxic impurities, and then separating a derivative product with a derivative agent structure; and (2) fragmenting the derivative product under a mass spectrum condition to generate the same ion fragments, and screening the unknown alkylated genotoxic impurities through ion fragment screening. The invention provides a method for non-targeting screening of alkylated genotoxic impurities by derivatization-ultra-high performance liquid chromatography-high resolution mass spectrometry, and the method comprises the following steps: based on the reaction characteristics of amine compounds and alkylated genotoxic impurities, selecting the amine compounds as a derivatization reagent; according to the present invention, the specific ion fragment screening is performed according to the characteristic that the specific ion fragment is generated by fragmentation of the structure of the derivative reagent under the mass spectrum condition, such that the screening of the unknown alkylation genotoxic impurity is achieved, and the result shows that the specificity of the method provided by the present invention is good.

Description

technical field [0001] The invention relates to the technical field of genotoxic impurity detection, in particular to a non-targeted screening method for alkylated genotoxic impurities. Background technique [0002] The information disclosed in this Background of the Invention is only for enhancement of understanding of the general background of the invention and should not necessarily be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person of ordinary skill in the art. [0003] The genetic material of the human body is DNA, which mainly contains four bases: adenine, guanine, cytosine and thymine. The nitrogen and oxygen above pyrimidines and purines are rich in electrons and are prone to substitution reactions with electrophilic alkylated impurities, resulting in the mutation of the bases modified by these genotoxic impurities. Alkylation reagents are commonly used reagents in drug synthesis, and there ma...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06G01N30/72
CPCG01N30/02G01N30/06G01N30/72G01N2030/067
Inventor 杭宝建石峰巩丽萍咸瑞卿王维剑李军薛维丽张迅杰李春焕
Owner SHANDONG INST FOR FOOD & DRUG CONTROL
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