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Method for simultaneously detecting methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in tubulin inhibitor bulk drug

A technology of methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate is applied in the field of analysis and testing to achieve the effects of high sensitivity, good repeatability, and quick and simple operation

Active Publication Date: 2021-04-30
SHENZHEN NEPTUNUS PHARMA RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is still a lack of a method with high detection sensitivity, simple and easy-to-operate gas chromatography-mass spectrometry for the simultaneous detection of methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in raw materials

Method used

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  • Method for simultaneously detecting methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in tubulin inhibitor bulk drug
  • Method for simultaneously detecting methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in tubulin inhibitor bulk drug
  • Method for simultaneously detecting methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in tubulin inhibitor bulk drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1 Gas phase-mass spectrometry detects the detection method of methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate simultaneously

[0041] (1) Preparation of test solution

[0042] Precisely weigh 50 mg of HW130 raw material drug as the test product and place it in a 10 mL volumetric flask, add the solvent isopropanol to the mark, shake well, ultrasonicate for 5 minutes, and filter it through a filter membrane as the test solution.

[0043] (2) Preparation of reference substance stock solution

[0044] Accurately weigh about 50mg of methyl trifluoromethanesulfonate reference substance into a 50mL volumetric flask, make up to the mark with solvent and mix well. Accurately weigh about 50mg of ethyl trifluoromethanesulfonate reference substance into a 50mL volumetric flask, make up to the mark with solvent and mix well. Precisely pipette 500 μL of each of the above two solutions into a 10 mL volumetric flask, make up to the mark with solvent an...

Embodiment 2

[0054] The limit of detection and limit of quantification of the gas phase-mass spectrometry detection method of embodiment 2

[0055] According to the method of Example 1, the reference substance solution was prepared and detected by gas chromatography-mass spectrometry. According to the detection data of the reference substance, according to the calculation formula of the detection limit of the method: LOD=3C / (S / N), the detection limit of the gas phase-mass spectrometry detection method is calculated. According to the calculation formula LOQ=10C / (S / N) of the quantitative limit of the method, the quantitative limit of the gas phase-mass spectrometry detection method is calculated. The results are shown in Table 1:

[0056] Table 1 The detection limit of gas phase-mass spectrometry detection method

[0057]

[0058] Table 2 Quantitative limit of gas phase-mass spectrometry detection method

[0059]

Embodiment 3

[0060] The linear range of embodiment 3 gas phase-mass spectrometry detection method

[0061] According to the method of embodiment 1, prepare reference substance solution, get reference substance stock solution and prepare a series of linearity test solutions (50%, 75%, 100%, 150%, 200%) from LOQ to 200% concentration preparation, every part of solution Inject the sample once and calculate the equation and regression coefficient (r). The results are shown in Table 3.

[0062] Table 3 The linear range of the gas phase-mass spectrometry detection method

[0063]

[0064] It can be seen from the above experimental results that the gas phase-mass spectrometry detection method has a good linear relationship within the detection range, and can accurately quantify the content of the impurities methyl triflate and ethyl triflate.

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Abstract

The invention discloses a method for simultaneously detecting genotoxic impurities including methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in tubulin inhibitor bulk drugs, and the bulk drugs are (3Z, 6Z)-3-[(E)-3-(5-tert-butyl)-1H-imidazolyl-4-yl) methylene]-6-((E)-3-(3-fluorophenyl)-2-propylene subunit)piperazine-2, 5-diketone. The method comprises the following steps: (1) taking a test sample of the raw material medicine, adding isopropanol, uniformly shaking, carrying out ultrasonic treatment, filtering, taking the subsequent filtrate, and introducing a sample to determine trifluoromethanesulfonic acid methyl ester and trifluoromethanesulfonic acid ethyl ester; wherein methyl trifluoromethanesulfonate reacts in isopropanol to generate methyl isopropyl ether, and ethyl trifluoromethanesulfonate reacts in isopropanol to generate ethyl isopropyl ether; and (2) detection conditions: taking polyethylene glycol modified by nitro terephthalic acid as a capillary column of a stationary phase, and determining by adopting a gas chromatograph-mass spectrometer. According to the method, the methyl trifluoromethanesulfonate and the ethyl trifluoromethanesulfonate in the tubulin inhibitor bulk drug can be qualitatively and quantitatively detected simply, quickly and efficiently at the same time.

Description

technical field [0001] The invention belongs to the field of analysis and testing, and in particular relates to a method for simultaneously detecting genotoxic impurities methyl trifluoromethanesulfonate and ethyl trifluoromethanesulfonate in tubulin inhibitor raw materials by gas chromatography-mass spectrometry. Background technique [0002] Sulfonic acids such as methanesulfonic acid and benzenemethanesulfonic acid are used as the acid radical of the drug, which can increase the solubility or adjust the pH of the drug. However, in the process of drug synthesis, they are easy to generate alkyl sulfonates such as methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and methyl benzenesulfonate ( MBS), ethyl benzenesulfonate (EBS), these substances can undergo alkylation reactions with DNA, which may become the cause of cancer. Trifluoromethanesulfonic acid is an acid radical reagent commonly used in the production of raw materials. Methyl trifluoromethanesulfonate a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/60G01N30/72G01N30/86
CPCG01N30/02G01N30/06G01N30/6078G01N30/7206G01N30/8679Y02P20/55
Inventor 石涛郭青孔萌卢晓莹栾升霖唐田冯汉林
Owner SHENZHEN NEPTUNUS PHARMA RES INST CO LTD
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