CN112763585A - Method for determining benzene impurity content in sulfadiazine or sulfadiazine derivative - Google Patents

Method for determining benzene impurity content in sulfadiazine or sulfadiazine derivative Download PDF

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CN112763585A
CN112763585A CN202011020931.XA CN202011020931A CN112763585A CN 112763585 A CN112763585 A CN 112763585A CN 202011020931 A CN202011020931 A CN 202011020931A CN 112763585 A CN112763585 A CN 112763585A
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benzene
sulfadiazine
reference substance
test sample
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邱伟杰
袁莉莉
黄志云
刘明威
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Nanhai Beisha Pharmaceutical Co ltd
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
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Abstract

The invention discloses a method for measuring the content of benzene impurities in sulfadiazine or sulfadiazine derivatives, which comprises the following steps: s1, preparing a blank solvent sample, a reference sample and a test sample; s2, respectively carrying out gas chromatography tests on the blank solvent sample, the reference sample and the test sample by using a gas chromatograph to obtain a chromatogram; s3, screening the corresponding absorption peaks of the benzene in the chromatogram by comparing the chromatograms of the blank solvent sample, the reference sample and the test sample, and calculating the absorption peak area A of the benzene in the reference sampleControlAnd the absorption peak area A of benzene in the test sampleSample (A)(ii) a S4, calculating the content of benzene in the sulfadiazine or sulfadiazine derivative sample by using a formula.

Description

Method for determining benzene impurity content in sulfadiazine or sulfadiazine derivative
Technical Field
The invention relates to the technical field of chemical analysis, in particular to a method for measuring the content of benzene impurities in sulfadiazine or sulfadiazine derivatives.
Background
Sulfadiazine has broad spectrum and strong antibacterial activity, has inhibition effect on gram-positive bacteria and gram-negative bacteria, can be used for treating infection of meningococcus, pneumococcus, gonococcus and lysostaphin, can enter cerebrospinal fluid through blood brain barrier, and has been used as the first choice medicine for treating epidemic meningitis. The sulfadiazine and the derivatives thereof can generate a trace of benzene impurities which are difficult to separate in the synthesis process, and the prior art is lack of a measurement means for the benzene content.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the method for determining the benzene impurity content in sulfadiazine or the sulfadiazine derivative, which has high reliability and high accuracy of test results.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: a method for measuring the content of benzene impurities in sulfadiazine or sulfadiazine derivatives comprises the following steps:
s1, transferring dimethyl sulfoxide with a volume V into a headspace bottle, and then sealing a gland of the headspace bottle to prepare a blank solvent sample; weighing mControlDiluting the benzene reference substance by using dimethyl sulfoxide to prepare a reference substance diluted solution, putting the reference substance diluted solution with the volume V into a headspace bottle, and sealing a gland of the headspace bottle to prepare a reference sample; weighing mSample (A)Diluting the sulfadiazine or sulfadiazine derivative sample by using dimethyl sulfoxide to prepare a test sample diluted solution, putting the test sample diluted solution with the volume V into a headspace bottle, and then sealing a gland of the headspace bottle to prepare a test sample;
s2, respectively carrying out gas chromatography tests on the blank solvent sample, the reference sample and the test sample by using a gas chromatograph to obtain a chromatogram;
s3, screening the corresponding absorption peaks of the benzene in the chromatogram by comparing the chromatograms of the blank solvent sample, the reference sample and the test sample, and calculating the absorption peak area A of the benzene in the reference sampleControlAnd the absorption peak area A of benzene in the test sampleSample (A)；
S4, calculating the content of benzene in the sulfadiazine or sulfadiazine derivative sample by using the following formula:
Figure RE-GDA0002934357400000011
wherein p is the purity of benzene reference substance, NControlIs the dilution factor, N, of the benzene control in the control sampleSample (A)Is the dilution factor of sulfadiazine or sulfadiazine derivative in the test sample.
Preferably, the sulfadiazine derivative comprises sulfadiazine or sulfadimidine sodium.
Preferably, the volume of V is 1-3 ml, and the volume of the headspace bottle is 20 ml.
Preferably, in step S1, the method for preparing the reference product diluted solution includes the following steps: weighing mControlPlacing the benzene reference substance in a 100ml measuring flask, diluting the benzene reference substance to a scale by using dimethyl sulfoxide, shaking the benzene reference substance uniformly, transferring 2ml of the benzene reference substance, placing the benzene reference substance in the 100ml measuring flask, diluting the benzene reference substance to the scale by using the dimethyl sulfoxide, and shaking the benzene reference substance uniformly to obtain a reference substance stock solution; taking 3ml of the reference substance stock solution, placing the reference substance stock solution in a 20ml measuring flask, diluting the reference substance stock solution to the scale with dimethyl sulfoxide, and shaking up to prepare a reference substance diluted solution.
The invention has the beneficial effects that: the invention utilizes the gas chromatography to measure the content of the dimethyl sulfoxide, and the test result is reliable and has high accuracy. Can be suitable for most chemical analysis laboratories, and is convenient for popularization and use.
Detailed Description
The claimed concept will now be described in further detail with reference to specific embodiments.
Example one
The method for measuring the benzene impurity content in the embodiment comprises the following steps:
s1, transferring 3ml of dimethyl sulfoxide into a 20ml of headspace bottle, and then sealing a gland of the headspace bottle to prepare a blank solvent sample.
Weighing mControlPlacing the benzene reference substance in a 100ml measuring flask, diluting the benzene reference substance to a scale by using dimethyl sulfoxide, shaking the benzene reference substance uniformly, transferring 2ml of the benzene reference substance, placing the benzene reference substance in the 100ml measuring flask, diluting the benzene reference substance to the scale by using the dimethyl sulfoxide, and shaking the benzene reference substance uniformly to obtain a reference substance stock solution; taking 3ml of the reference substance stock solution, placing the reference substance stock solution in a 20ml measuring flask, diluting the reference substance stock solution to the scale with dimethyl sulfoxide, shaking the reference substance stock solution uniformly to prepare a reference substance diluted solution, taking the reference substance diluted solution with the volume of 3ml, placing the reference substance diluted solution in a 20ml headspace flask, and then placing the reference substance diluted solution in the 20ml headspace flaskThe cap of the headspace bottle was sealed to prepare a control sample.
Weighing mSample (A)Diluting the sulfadiazine sample by using dimethyl sulfoxide to prepare a test sample diluted solution, putting the test sample diluted solution with the volume of 3ml into a 20ml headspace bottle, and then sealing a gland of the headspace bottle to prepare a test sample.
And S2, respectively carrying out gas chromatography tests on the blank solvent sample, the reference sample and the test sample by using a gas chromatograph to obtain a chromatogram. The chromatographic parameters and headspace parameters in this example are as follows:
Figure RE-GDA0002934357400000021
Figure RE-GDA0002934357400000031
s3, screening the corresponding absorption peaks of the benzene in the chromatogram by comparing the chromatograms of the blank solvent sample, the reference sample and the test sample, and calculating the absorption peak area A of the benzene in the reference sampleControlAnd the absorption peak area A of benzene in the test sampleSample (A)；
S4, calculating the content of benzene in the sulfadiazine sample by using the following formula:
Figure RE-GDA0002934357400000032
wherein p is the purity of benzene reference substance, NControlIs the dilution factor, N, of the benzene control in the control sampleSample (A)Is the dilution factor of sulfadiazine in the test sample.
Example two
The method for measuring the benzene impurity content in the embodiment comprises the following steps:
s1, transferring 3ml of dimethyl sulfoxide into a 20ml of headspace bottle, and then sealing a gland of the headspace bottle to prepare a blank solvent sample.
Weighing mControlBenzene controlPlacing the sample in a 100ml measuring flask, diluting the sample to the scale with dimethyl sulfoxide, shaking the sample evenly, transferring 2ml of the sample, placing the sample in the 100ml measuring flask, diluting the sample to the scale with dimethyl sulfoxide, and shaking the sample evenly to obtain a reference substance stock solution; taking 3ml of the reference substance stock solution, placing the reference substance stock solution in a 20ml measuring flask, diluting the reference substance stock solution to the scale with dimethyl sulfoxide, shaking the reference substance stock solution uniformly to prepare a reference substance diluted solution, taking 3ml of the reference substance diluted solution, placing the reference substance diluted solution in a 20ml headspace flask, and then sealing a gland of the headspace flask to prepare a reference sample.
Weighing mSample (A)Diluting the sulfamethazine sample by using dimethyl sulfoxide to prepare a test sample diluted solution, putting the test sample diluted solution with the volume of 3ml into a 20ml headspace bottle, and then sealing a gland of the headspace bottle to prepare a test sample.
S2, respectively carrying out gas chromatography tests on the blank solvent sample, the reference sample and the test sample by using a gas chromatograph to obtain a chromatogram; the chromatographic parameters and headspace parameters in this example are as follows:
Figure RE-GDA0002934357400000033
Figure RE-GDA0002934357400000041
s3, screening the corresponding absorption peaks of the benzene in the chromatogram by comparing the chromatograms of the blank solvent sample, the reference sample and the test sample, and calculating the absorption peak area A of the benzene in the reference sampleControlAnd the absorption peak area A of benzene in the test sampleSample (A)；
S4, calculating the content of benzene in the sulfamethazine sample by using the following formula:
Figure RE-GDA0002934357400000042
wherein p is the purity of benzene reference substance, NControlIs the dilution factor, N, of the benzene control in the control sampleSample (A)Is the dilution factor of sulfamethazine in the test sample.
EXAMPLE III
The method for measuring the benzene impurity content in the embodiment comprises the following steps:
s1, transferring dimethyl sulfoxide with the volume of 1ml into a 20ml headspace bottle, and then sealing a gland of the headspace bottle to prepare a blank solvent sample.
Weighing mControlPlacing the benzene reference substance in a 100ml measuring flask, diluting the benzene reference substance to a scale by using dimethyl sulfoxide, shaking the benzene reference substance uniformly, transferring 2ml of the benzene reference substance, placing the benzene reference substance in the 100ml measuring flask, diluting the benzene reference substance to the scale by using the dimethyl sulfoxide, and shaking the benzene reference substance uniformly to obtain a reference substance stock solution; taking 3ml of the reference substance stock solution, placing the reference substance stock solution in a 20ml measuring flask, diluting the reference substance stock solution to the scale with dimethyl sulfoxide, shaking the reference substance stock solution uniformly to prepare a reference substance diluted solution, taking 1ml of the reference substance diluted solution in a 20ml headspace flask, and then sealing a gland of the headspace flask to prepare a reference sample.
Weighing mSample (A)Diluting the sulfadimidine sodium sample by using dimethyl sulfoxide to prepare a test sample diluted solution, putting the test sample diluted solution with the volume of 1ml into a 20ml headspace bottle, and then sealing a gland of the headspace bottle to prepare a test sample.
S2, respectively carrying out gas chromatography tests on the blank solvent sample, the reference sample and the test sample by using a gas chromatograph to obtain a chromatogram; the chromatographic parameters and headspace parameters in this example are as follows:
Figure RE-GDA0002934357400000051
s3, screening the corresponding absorption peaks of the benzene in the chromatogram by comparing the chromatograms of the blank solvent sample, the reference sample and the test sample, and calculating the absorption peak area A of the benzene in the reference sampleControlAnd the absorption peak area A of benzene in the test sampleSample (A)；
S4, calculating the content of benzene in the sulfadimidine sodium sample by using the following formula:
Figure RE-GDA0002934357400000052
wherein p is the purity of benzene reference substance, NControlIs the dilution factor, N, of the benzene control in the control sampleSample (A)Is the dilution factor of the sulfadimidine sodium in the test sample.
The benzene impurity content testing method of the invention is verified to verify the accuracy of the testing method, including system adaptability testing and linear testing.
Wherein the procedure of the system adaptability test is to inject a blank solution after the chromatographic system is balanced, then continuously inject 6 reference dilution solutions for the examples one to three, calculate the Relative Standard Deviation (RSD) of the benzene peak area, and the system adaptability test result is as follows:
Figure RE-GDA0002934357400000061
Figure RE-GDA0002934357400000062
Figure RE-GDA0002934357400000063
Figure RE-GDA0002934357400000071
the process of the linearity test is: the control stock solution of the first example was diluted to linear solutions of different concentrations according to the following table, and the linear solutions of each concentration were continuously injected into two needles to calculate the average value of the benzene peak area. Taking the concentration of benzene as a horizontal coordinate and the peak area as a vertical coordinate, performing linear regression analysis, and calculating a correlation coefficient.
Linear solution Linear stock solution (mL) was measured Volumetric flask(mL)
L1 4 100
L2 1 20
L3 2 20
L4 3 20
L5 10 50
L6 5 20
The results of the linearity test are as follows:
Figure RE-GDA0002934357400000072
the above-described embodiments are merely preferred embodiments of the present invention, which is not intended to limit the present invention in any way. Those skilled in the art can make many changes and modifications to the disclosed embodiments, or modify equivalent embodiments to practice the disclosed embodiments, without departing from the scope of the disclosed embodiments. Therefore, equivalent variations made according to the idea of the present invention should be covered within the protection scope of the present invention without departing from the contents of the technical solution of the present invention.

Claims (4)

1. A method for measuring the content of benzene impurities in sulfadiazine or sulfadiazine derivatives is characterized by comprising the following steps:
s1, transferring dimethyl sulfoxide with a volume V into a headspace bottle, and then sealing a gland of the headspace bottle to prepare a blank solvent sample; weighing mControlDiluting with dimethyl sulfoxide to obtain reference substance diluted solution, and diluting with volume VPlacing the released solution in a headspace bottle, and then sealing a gland of the headspace bottle to prepare a control sample; weighing mSample (A)Diluting the sulfadiazine or sulfadiazine derivative sample by using dimethyl sulfoxide to prepare a test sample diluted solution, putting the test sample diluted solution with the volume V into a headspace bottle, and then sealing a gland of the headspace bottle to prepare a test sample;
s2, respectively carrying out gas chromatography tests on the blank solvent sample, the reference sample and the test sample by using a gas chromatograph to obtain a chromatogram;
s3, screening the corresponding absorption peaks of the benzene in the chromatogram by comparing the chromatograms of the blank solvent sample, the reference sample and the test sample, and calculating the absorption peak area A of the benzene in the reference sampleControlAnd the absorption peak area A of benzene in the test sampleSample (A)；
S4, calculating the content of benzene in the sulfadiazine or sulfadiazine derivative sample by using the following formula:
Figure RE-FDA0002989462780000011
wherein p is the purity of benzene reference substance, NControlIs the dilution factor, N, of the benzene control in the control sampleSample (A)Is the dilution factor of sulfadiazine or sulfadiazine derivative in the test sample.
2. The method for determining the content of benzene impurities in sulfadiazine or a sulfadiazine derivative according to claim 1, is characterized in that: the sulfadiazine derivative comprises sulfadiazine or sulfadimidine sodium.
3. The method for determining the content of benzene impurities in sulfadiazine or a sulfadiazine derivative according to claim 1, is characterized in that: the volume of V is 1-3 ml, and the volume of the headspace bottle is 20 ml.
4. The sulfadiazine or sulfadiazine derivative of claim 1The method for measuring the content of the impurities is characterized by comprising the following steps: in step S1, the method for preparing the reference substance diluted solution includes the following steps: weighing mControlPlacing the benzene reference substance in a 100ml measuring flask, diluting the benzene reference substance to a scale by using dimethyl sulfoxide, shaking the benzene reference substance uniformly, transferring 2ml of the benzene reference substance, placing the benzene reference substance in the 100ml measuring flask, diluting the benzene reference substance to the scale by using the dimethyl sulfoxide, and shaking the benzene reference substance uniformly to obtain a reference substance stock solution; taking 3ml of the reference substance stock solution, placing the reference substance stock solution in a 20ml measuring flask, diluting the reference substance stock solution to the scale with dimethyl sulfoxide, and shaking up to prepare a reference substance diluted solution.
CN202011020931.XA 2020-09-25 2020-09-25 Method for determining benzene impurity content in sulfadiazine or sulfadiazine derivative Pending CN112763585A (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113533591A (en) * 2021-06-18 2021-10-22 山东罗欣药业集团恒欣药业有限公司 GC analysis method for benzene and paraldehyde in cefprozil
CN113533591B (en) * 2021-06-18 2022-08-23 山东罗欣药业集团恒欣药业有限公司 GC analysis method for benzene and paraldehyde in cefprozil

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