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Method for determining content of dimethyl sulfate in clopidogrel hydrogen sulfate

A technology of clopidogrel hydrogen sulfate and dimethyl sulfate, which is applied in the field of medicine, can solve the problems of not having sensitive ultraviolet absorbing groups, dimethyl sulfate has high polarity, and is easy to hydrolyze, and achieves good solution stability, Good linear relationship, good precision and accuracy

Inactive Publication Date: 2020-08-25
JIANGSU LIANHUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Dimethyl sulfate is highly polar, does not have sensitive UV-absorbing groups, and is easily hydrolyzed
It is difficult to use gas phase, liquid chromatography and other conventional analysis methods to directly determine its trace amount
Moreover, clopidogrel bisulfate has its specificity in structure, and it has an ester group functional group similar to that of dimethyl sulfate. If it is analyzed by derivatization method, there will be a risk of false positive

Method used

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  • Method for determining content of dimethyl sulfate in clopidogrel hydrogen sulfate
  • Method for determining content of dimethyl sulfate in clopidogrel hydrogen sulfate
  • Method for determining content of dimethyl sulfate in clopidogrel hydrogen sulfate

Examples

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Embodiment 1

[0023] A method for measuring dimethyl sulfate content in clopidogrel hydrogen sulfate, adopting gas phase-mass spectrometry to measure the content of dimethyl sulfate in clopidogrel hydrogen sulfate, specifically comprises the following steps:

[0024] (1) Preparation of reference substance solution: take an appropriate amount of dimethyl sulfate, accurately weighed, add methanol to dissolve and make a solution containing about 0.5 μg of dimethyl sulfate per 1 mL as the reference substance solution;

[0025] Preparation of the test solution: Accurately weigh 0.33g of clopidogrel hydrogen sulfate into a 10mL measuring bottle, dissolve with methanol and set the volume to the mark, then add an appropriate amount of molecular sieve to remove water to obtain a blank test solution;

[0026] According to the physical and chemical properties and test experience of dimethyl sulfate, dimethyl sulfate is easy to degrade at room temperature, so all solutions are stored in an environment b...

Embodiment 2

[0032] The method verification of the detection method in Example 1 was carried out from the aspects of specificity, linear range, precision, limit of quantification, detection limit, recovery rate, repeatability, and solution stability. The following detailed descriptions are given.

[0033] 1) Specific test

[0034] (1) blank solvent: methanol;

[0035] (2) Blank test solution: take 0.33 g of clopidogrel hydrogen sulfate obtained from production, accurately weigh it, put it in a 10 mL measuring bottle, dissolve it with methanol and set the volume to the mark, then add an appropriate amount of molecular sieve to remove water, and use it as a blank supply Test solution;

[0036] (3) Control solution: take an appropriate amount of dimethyl sulfate, accurately weighed, add methanol to dissolve and make a solution containing 0.5 μg of dimethyl sulfate per 1 mL as the reference solution;

[0037] Take 2 μL of each of the above solutions for direct injection, and record the chrom...

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Abstract

The invention discloses a method for determining the content of dimethyl sulfate in clopidogrel hydrogen sulfate, and belongs to the technical field of medicines. The method adopts a gas chromatograph-mass spectrometer to determine the content of dimethyl sulfate in clopidogrel hydrogen sulfate, and comprises the following steps: firstly, preparing a test solution, and storing the prepared solution in an environment below 0 DEG C for later use; then setting detection conditions of a gas chromatograph-mass spectrometer; after the sample introduction condition is met, starting sample introduction, completing the detection process, and rcording a chromatogram. The method for detecting the dimethyl sulfate in the clopidogrel hydrogen sulfate is high in detection sensitivity, the linear range of the dimethyl sulfate is within the range of 5%-500% of the limit concentration, and the linear relation between the concentration and the peak area is good. According to recovery rate, repeatabilityand sample injection precision tests, the precision and accuracy of the method are good. A reference substance solution stability test shows that the reference substance solution has good stability after being placed at 0 DEG C or below for 6 hours.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a method for measuring the content of dimethyl sulfate in clopidogrel bisulfate. Background technique [0002] Sulfuric acid is used in the production of clopidogrel bisulfate. When sulfuric acid encounters methanol, it may produce dimethyl sulfate, a potentially genotoxic substance. Referring to ICH M7, the acceptable intake of dimethyl sulfate is 1.5 μg / day, so dimethyl sulfate should be dealt with The content is strictly tested and controlled. Dimethyl sulfate is highly polar, does not have sensitive UV-absorbing groups, and is easily hydrolyzed. It is difficult to directly determine its trace amount by gas phase, liquid chromatography and other conventional analysis methods. Moreover, clopidogrel bisulfate has its specificity in structure, and it has an ester functional group similar in structure to dimethyl sulfate, so there is a risk of false positives if analyzed by der...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/72
CPCG01N30/02G01N30/72
Inventor 贾志祥褚青松牛犇黄坤赵健
Owner JIANGSU LIANHUAN PHARMA
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