CN114660209A - Method for determining content of benzene impurities in carbomer by using HS-GC external standard method - Google Patents
Method for determining content of benzene impurities in carbomer by using HS-GC external standard method Download PDFInfo
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 title claims abstract description 345
- 229920002125 Sokalan® Polymers 0.000 title claims abstract description 31
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 229960001631 carbomer Drugs 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 19
- 238000010812 external standard method Methods 0.000 title claims abstract description 16
- 239000012535 impurity Substances 0.000 title claims abstract description 13
- 239000007789 gas Substances 0.000 claims abstract description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000007788 liquid Substances 0.000 claims abstract description 5
- 239000012159 carrier gas Substances 0.000 claims abstract description 4
- 239000004205 dimethyl polysiloxane Substances 0.000 claims abstract description 4
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims abstract description 4
- 239000001307 helium Substances 0.000 claims abstract description 4
- 229910052734 helium Inorganic materials 0.000 claims abstract description 4
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 54
- 239000000126 substance Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 239000012086 standard solution Substances 0.000 claims description 27
- 239000011550 stock solution Substances 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 13
- 239000012085 test solution Substances 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000000523 sample Substances 0.000 claims description 9
- 239000012490 blank solution Substances 0.000 claims description 6
- 238000005070 sampling Methods 0.000 claims description 6
- 238000004458 analytical method Methods 0.000 claims description 5
- 239000012488 sample solution Substances 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000007865 diluting Methods 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 238000004817 gas chromatography Methods 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 238000009614 chemical analysis method Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 description 5
- 239000002537 cosmetic Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 238000000518 rheometry Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- -1 cyanopropyl Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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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
- G01N30/62—Detectors specially adapted therefor
- G01N30/64—Electrical detectors
- G01N30/68—Flame ionisation detectors
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Abstract
The invention discloses a method for determining benzene impurity content in carbomer by using an HS-GC external standard method, which relates to the technical field of chemical analysis methods, and is characterized in that a headspace gas chromatograph is used for detecting carbomer containing benzene and quantitatively analyzing by using the external standard method, a capillary column taking 6% cyanopropylphenyl-94% dimethylpolysiloxane as stationary liquid or a chromatographic column with equivalent polarity is used as a chromatographic column, nitrogen or helium is used as carrier gas, and a flame ionization detector is used; the method has the advantages of high precision, good reproducibility, simplicity, practicability, convenience and reliability, is particularly suitable for carbomer with the benzene content of less than 2ppm, and can accurately measure the content of benzene impurities in the carbomer.
Description
The technical field is as follows:
the invention relates to the technical field of chemical analysis methods, in particular to a method for determining the content of benzene impurities in carbomer by using an HS-GC external standard method.
The background art comprises the following steps:
carbomers (carbomers) are a class of crosslinked acrylic polymers that are synthetic water-soluble polymers. Carbomer is firstly manufactured and marketed by American gulde corporation, and a series of carbomer products produced by domestic Anhui Newman fine chemical industry limited enterprises are rich in variety and excellent in performance. Carbomers, as water-soluble rheology modifying thickeners, are commonly used to adjust the viscosity of liquids, to improve the thixotropic properties of gel systems and to increase the stability of products, playing a very important role in the pharmaceutical, cosmetic and technical product sectors. Because the carbomer has stable and safe chemical properties, no anaphylactic reaction and good compatibility with other auxiliary materials, the carbomer is a medicinal auxiliary material with multiple purposes, is widely applied to the relevant industrial fields of pharmaceutical industry and the like, and is mainly used as a thickening agent, a suspending agent, an emulsifying agent, an adhesive, a rheology modifying agent (a wetting agent, a lubricating agent, a suspending agent and a stabilizing agent) and the like in medicaments, and can be used as a bioadhesive material, a framework material of a controlled-release agent, an adhesive of a tablet, a film coating material of a solid preparation, a thickening agent of ointment and the like, an excipient of other medicinal preparations and the like.
Carbomer as a pharmaceutical adjuvant was collected in the national pharmacopoeias of europe, british, usa and the like in 1957, and the pharmacopoeias of the 2000 edition of China have been included in China. Because the reaction solvent used in the production of carbomer brings the risk of benzene impurity, and benzene is already listed as a carcinogen in the technical Specification for cosmetic safety in 2015 as a cosmetic forbidden component, the benzene content in carbomer in the pharmacopoeia of 2000 th edition in China and the pharmacopoeia of America/Europe and Japan must not be more than 2 ppm. The benzene content of the carbomer is therefore critical to the safety performance of the carbomer, especially if the carbomer is used for oral, ocular administration, the benzene content requirement is less than 0.5pppm, or even lower. Therefore, the method has important significance on accurate detection of the benzene impurity content in the carbomer.
The method for detecting benzene in carbomer in pharmacopoeia of 2000 th edition in China only regulates the detection value of benzene in carbomer to be not more than 2ppm, and cannot accurately calculate the content of benzene.
The invention content is as follows:
the invention aims to solve the technical problem of providing a method for determining the content of benzene impurities in carbomer by using an HS-GC external standard method, the method is particularly suitable for carbomer with the benzene content of less than 2ppm, can accurately determine the content of the benzene impurities in carbomer, and has the advantages of high precision, good reproducibility, simplicity, practicability, convenience and reliability.
The technical problem to be solved by the invention is realized by adopting the following technical scheme:
a method for determining the content of benzene impurities in carbomer by using an HS-GC external standard method comprises the following steps of detecting by using a headspace gas chromatograph, and carrying out quantitative analysis by using an external standard method, wherein the gas chromatographic analysis conditions are as follows: the chromatographic column adopts a capillary column (the thickness of the membrane is 1.8 mu m or 3 mu m) taking 6 percent of cyanopropylphenyl-94 percent of dimethylpolysiloxane as a stationary liquid or a chromatographic column with equivalent polarity, the length of the chromatographic column is 30m or 60m, and the inner diameter of the chromatographic column is 0.32mm or 0.53 mm; the initial column temperature was 40 ℃ and maintained at 40 ℃ for 20min, then increased to 240 ℃ at a ramp rate of 10 ℃/min and maintained at 240 ℃ for 20 min.
The gas chromatography condition analysis further comprises: nitrogen or helium is used as carrier gas, a flame ionization detector is adopted, the sample introduction temperature is kept at 140 ℃, and the detector temperature is kept at 250 ℃.
The sample injection is headspace sample injection, the equilibrium temperature is 80 ℃, and the equilibrium time is 60 min.
The method for determining the benzene impurity content in carbomer by using the HS-GC external standard method comprises the following specific steps:
(1) benzene standard stock solution preparation:
weighing 0.100g of benzene, placing the benzene into a 100.0mL volumetric flask with a small amount of dimethyl sulfoxide, adding dimethyl sulfoxide to a constant volume after the benzene is completely dissolved, and shaking up; then 1.0mL of solution is diluted to 100.0mL by water and shaken up to prepare a benzene standard stock solution A with the concentration of 10.000 mg/L;
diluting the benzene standard stock solution A with water to respectively prepare benzene standard stock solutions B, C, D, E, F with concentrations of 0.100mg/L, 0.050mg/L, 0.030mg/L, 0.010mg/L and 0.005 mg/L;
(2) preparing a test solution:
placing 50.0mg of a substance to be detected in a headspace bottle, adding 5.0mL of water and 1.0mL of dimethyl sulfoxide, immediately covering a bottle cap, and shaking up lightly to obtain a sample solution;
(3) preparation of benzene standard solution:
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution B, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution B;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution C, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution C;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution D, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution D;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution E, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution E;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution F, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution F;
(4) preparation of a benzene qualitative solution:
placing 5.0mL of water and 1.0mL of solution containing benzene in a headspace bottle, immediately covering a bottle cap, and shaking up lightly;
(5) preparing a blank solution:
placing 5.0mL of water and 1.0mL of dimethyl sulfoxide into a top empty bottle, immediately covering a bottle cap, and shaking up lightly;
(6) analysis by a headspace gas chromatograph:
extracting 1mL of gas in B, C, D, E, F headspace bottles of a benzene qualitative solution, a blank solution and a standard solution, feeding the gas into a chromatograph through headspace sampling, analyzing the gas, recording the peak area of benzene, drawing a standard curve by adopting an external standard method by taking the concentration of the benzene standard solution as a horizontal coordinate and taking half of the peak area as a vertical coordinate, and obtaining a standard curve regression equation;
extracting 1mL of gas in a headspace bottle of the test solution, feeding the gas into a chromatograph through headspace sampling to analyze the gas, recording the peak area of benzene, and calculating the concentration of the benzene in the test solution according to a standard curve regression equation;
(7) calculating the content of benzene in the substance to be detected:
calculating the content of benzene in the substance to be detected according to the following formula;
in the formula: w is the content of benzene in the substance to be detected, ug/g;
c, the concentration of benzene in the test solution is mg/L;
v, the constant volume of the substance to be detected, mL;
m-mass of substance to be detected, g.
The linear correlation coefficient R of the standard curve of the method is more than or equal to 99.9 percent.
Standard curves should be made for each experiment.
After the sample solution is heated and balanced by a headspace sample injector, a flame ionization detector is used for detection, and the retention time is used for qualitative determination and the external standard method is used for quantitative determination.
And (3) qualitative confirmation: under the above measurement conditions, chromatographic peaks of the test sample solution and the benzene standard solution and the benzene qualitative solution appear at the same retention time (+ -0.1 min), at which time the target analyte can be qualitatively confirmed.
The invention has the beneficial effects that:
(1) the determination method of the invention has high precision, good reproducibility, simple and easy operation, convenience and reliability.
(2) The assay of the invention is particularly useful for carbomers having a benzene content of less than 2 ppm.
(3) The determination method can accurately determine the content of benzene impurities in the carbomer.
Description of the drawings:
FIG. 1 is a standard curve of benzene content versus peak area;
FIG. 2 is a chromatogram of benzene standard solution E;
FIG. 3 is a chromatogram of a test solution.
The specific implementation mode is as follows:
in order to make the technical means, the original characteristics, the achieved purposes and the effects of the invention easy to understand, the invention is further explained by combining the specific embodiments and the drawings.
1. Preparing an instrument:
detecting with a headspace gas chromatograph, performing quantitative analysis with an external standard method, introducing sample in headspace at 80 deg.C for 60min, and using a capillary column (thickness of 1.8 μm or 3 μm) or a chromatographic column with equivalent polarity, with column length of 30m or 60m and column inner diameter of 0.32mm or 0.53mm, wherein 6% cyanopropyl phenyl-94% dimethylpolysiloxane is used as stationary liquid; the initial column temperature is 40 deg.C, and is maintained at 40 deg.C for 20min, then the temperature is raised to 240 deg.C at a rate of 10 deg.C/min, and is maintained at 240 deg.C for 20min, nitrogen or helium is used as carrier gas, a flame ionization detector is adopted, the sample introduction temperature is maintained at 140 deg.C, and the detector temperature is maintained at 250 deg.C.
2. Preparation of a benzene qualitative solution:
5.0mL of water and 1.0mL of benzene containing solution were placed in a headspace bottle, immediately capped and shaken gently.
3. Preparing a blank solution:
5.0mL of water and 1.0mL of dimethyl sulfoxide are placed in a top empty bottle, and a bottle cap is immediately covered and the bottle is shaken up lightly.
4. Drawing a standard curve:
1) benzene standard stock solution preparation:
weighing 0.100g of benzene, placing the benzene into a 100.0mL volumetric flask with a small amount of dimethyl sulfoxide, adding dimethyl sulfoxide to a constant volume after the benzene is completely dissolved, and shaking up; then 1.0mL of the solution was diluted to 100.0mL with water and shaken up to prepare a benzene standard stock solution A with a concentration of 10.000 mg/L.
Diluting the benzene standard stock solution A with water to respectively prepare benzene standard stock solutions B, C, D, E, F with concentrations of 0.100mg/L, 0.050mg/L, 0.030mg/L, 0.010mg/L and 0.005 mg/L.
2) Preparation of benzene standard solution:
placing 50.0mg of the substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution B, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution B.
Placing 50.0mg of the substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution C, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution C.
Placing 50.0mg of the substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution D, immediately covering a bottle cap, and shaking up lightly to obtain the benzene standard solution D.
Placing 50.0mg of the substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution E, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution E.
Putting 50.0mg of the substance to be detected into a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution F, immediately covering a bottle cap, and shaking up lightly to obtain the benzene standard solution F.
Extracting 1mL of gas in B, C, D, E, F headspace bottles of the benzene qualitative solution, the blank solution and the standard solution, feeding the gas into a chromatograph through headspace sampling, analyzing the gas, recording the peak area of benzene, drawing a standard curve (shown in figure 1) by adopting an external standard method by taking the concentration of the benzene standard solution as a horizontal coordinate and taking half of the peak area as a vertical coordinate, and obtaining a standard curve regression equation.
FIG. 2 is a chromatogram of benzene standard solution E, with a benzene peak at 11.483min and a peak area of 826.
5. Test solution:
50.0mg of the substance to be detected is placed in a headspace bottle, 5.0mL of water and 1.0mL of dimethyl sulfoxide are added, and then a bottle cap is immediately covered and the mixture is gently shaken to obtain a sample solution.
And (3) extracting 1mL of gas in a headspace bottle of the test solution, feeding the gas into a chromatograph for analysis through headspace sampling, recording the peak area of benzene, and calculating the concentration of the benzene in the test solution according to a standard curve regression equation.
The benzene content in the substance to be detected is calculated according to a formula and is 0.19 ppm.
FIG. 3 is a chromatogram of the test solution, showing a benzene peak at 11.467min and a peak area of 413.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (5)
1. A method for determining the benzene impurity content in carbomer by using an HS-GC external standard method is characterized by comprising the following steps: detecting by adopting a headspace gas chromatograph, and quantitatively analyzing by adopting an external standard method, wherein the gas chromatographic analysis conditions are as follows: the chromatographic column adopts a capillary column taking 6 percent cyanopropylphenyl-94 percent dimethylpolysiloxane as a stationary liquid or a chromatographic column with equivalent polarity, the length of the chromatographic column is 30m or 60m, and the inner diameter of the chromatographic column is 0.32mm or 0.53 mm; the initial column temperature was 40 ℃ and maintained at 40 ℃ for 20min, then increased to 240 ℃ at a ramp rate of 10 ℃/min and maintained at 240 ℃ for 20 min.
2. The method of claim 1, wherein: the capillary column has a membrane thickness of 1.8 μm or 3 μm.
3. The method of claim 1, wherein: the gas chromatography condition analysis further comprises: nitrogen or helium is used as carrier gas, a flame ionization detector is adopted, the sample introduction temperature is kept at 140 ℃, and the detector temperature is kept at 250 ℃.
4. The method of claim 1, wherein: the sample injection is headspace sample injection, the equilibrium temperature is 80 ℃, and the equilibrium time is 60 min.
5. The method according to any one of claims 1 to 4, characterized by the specific steps of:
(1) benzene standard stock solution preparation:
weighing 0.100g of benzene, placing the benzene into a 100.0mL volumetric flask with a small amount of dimethyl sulfoxide, adding dimethyl sulfoxide to a constant volume after the benzene is completely dissolved, and shaking up; then 1.0mL of solution is diluted to 100.0mL by water and shaken up to prepare a benzene standard stock solution A with the concentration of 10.000 mg/L;
diluting the benzene standard stock solution A with water to respectively prepare benzene standard stock solutions B, C, D, E, F with concentrations of 0.100mg/L, 0.050mg/L, 0.030mg/L, 0.010mg/L and 0.005 mg/L;
(2) preparing a test solution:
placing 50.0mg of a substance to be detected in a headspace bottle, adding 5.0mL of water and 1.0mL of dimethyl sulfoxide, immediately covering a bottle cap, and shaking up lightly to obtain a sample solution;
(3) benzene standard solution preparation:
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution B, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution B;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution C, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution C;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution D, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution D;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution E, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution E;
placing 50.0mg of a substance to be detected in a headspace bottle, adding 4.0mL of water, 1.0mL of dimethyl sulfoxide and 1.0mL of benzene standard stock solution F, immediately covering a bottle cap, and shaking up lightly to obtain benzene standard solution F;
(4) preparation of a benzene qualitative solution:
placing 5.0mL of water and 1.0mL of solution containing benzene in a headspace bottle, immediately covering a bottle cap, and shaking up lightly;
(5) preparing a blank solution:
placing 5.0mL of water and 1.0mL of dimethyl sulfoxide into a top empty bottle, immediately covering a bottle cap, and shaking up lightly;
(6) analysis by a headspace gas chromatograph:
extracting 1mL of gas in B, C, D, E, F headspace bottles of a benzene qualitative solution, a blank solution and a standard solution, feeding the gas into a chromatograph through headspace sampling, analyzing the gas, recording the peak area of benzene, drawing a standard curve by adopting an external standard method by taking the concentration of the benzene standard solution as a horizontal coordinate and taking half of the peak area as a vertical coordinate, and obtaining a standard curve regression equation;
extracting 1mL of gas in a headspace bottle of the test solution, feeding the gas into a chromatograph through headspace sampling to analyze the gas, recording the peak area of benzene, and calculating the concentration of the benzene in the test solution according to a standard curve regression equation;
(7) calculating the content of benzene in the substance to be detected:
calculating the content of benzene in the substance to be detected according to the following formula;
in the formula: w is the content of benzene in the substance to be detected, ug/g;
c, the concentration of benzene in the test solution is mg/L;
v, the constant volume of the substance to be detected, mL;
m represents the mass of the substance to be detected in g.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106153749A (en) * | 2015-04-07 | 2016-11-23 | 江苏宝众宝达药业有限公司 | The method of residual solvent in inspection chlophedianol hydrochloride Starting material medicine |
| CN113125584A (en) * | 2019-12-30 | 2021-07-16 | 成都百裕制药股份有限公司 | Method for detecting benzene in rivaroxaban by combining HS-GC/MS |
| CN113514566A (en) * | 2020-04-10 | 2021-10-19 | 昆药集团股份有限公司 | Method for detecting potential residual solvent benzene in homopiperazine |
-
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- 2022-02-28 CN CN202210188769.5A patent/CN114660209A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106153749A (en) * | 2015-04-07 | 2016-11-23 | 江苏宝众宝达药业有限公司 | The method of residual solvent in inspection chlophedianol hydrochloride Starting material medicine |
| CN113125584A (en) * | 2019-12-30 | 2021-07-16 | 成都百裕制药股份有限公司 | Method for detecting benzene in rivaroxaban by combining HS-GC/MS |
| CN113514566A (en) * | 2020-04-10 | 2021-10-19 | 昆药集团股份有限公司 | Method for detecting potential residual solvent benzene in homopiperazine |
Non-Patent Citations (4)
| Title |
|---|
| 宋敏;赵朝群;周永福;: "气相色谱法测定复方红豆杉胶囊中七种有机溶剂残留量", 黑龙江中医药, no. 06 * |
| 徐丽;陆晨光;: "顶空气相色谱法测定二苯乙酮中的苯含量", 山东化工, no. 19 * |
| 李淑丽;韦林洪;殷义平;: "埃索美拉唑钠残留溶剂苯的测定", 化学研究与应用, no. 03 * |
| 章为;李文波;李晓燕;王伟姣;谭桂山;: "顶空气相色谱法同时测定甲苯磺酸妥舒沙星原料药中6种有机溶剂的残留量", 中国药房, no. 06 * |
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