CN116858961A - Analysis method for bromoethyl acetate content in cephalosporin drugs - Google Patents
Analysis method for bromoethyl acetate content in cephalosporin drugs Download PDFInfo
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- RGHQKFQZGLKBCF-UHFFFAOYSA-N 2-bromoethyl acetate Chemical compound CC(=O)OCCBr RGHQKFQZGLKBCF-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 238000004458 analytical method Methods 0.000 title claims abstract description 28
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 229940079593 drug Drugs 0.000 title claims abstract description 19
- 229930186147 Cephalosporin Natural products 0.000 title claims abstract description 17
- 229940124587 cephalosporin Drugs 0.000 title claims abstract description 17
- 150000001780 cephalosporins Chemical class 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract description 31
- 238000002347 injection Methods 0.000 claims abstract description 17
- 239000007924 injection Substances 0.000 claims abstract description 17
- 229960001668 cefuroxime Drugs 0.000 claims abstract description 16
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 239000013558 reference substance Substances 0.000 claims abstract description 11
- 239000000523 sample Substances 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 28
- 239000007789 gas Substances 0.000 claims description 13
- 238000012360 testing method Methods 0.000 claims description 13
- 239000012488 sample solution Substances 0.000 claims description 11
- 239000012086 standard solution Substances 0.000 claims description 11
- 238000007865 diluting Methods 0.000 claims description 8
- 238000001819 mass spectrum Methods 0.000 claims description 8
- 239000011550 stock solution Substances 0.000 claims description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- 239000012159 carrier gas Substances 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 5
- 238000004817 gas chromatography Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 239000001307 helium Substances 0.000 claims description 3
- 229910052734 helium Inorganic materials 0.000 claims description 3
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 230000010355 oscillation Effects 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 238000004445 quantitative analysis Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000001514 detection method Methods 0.000 abstract description 14
- 238000001914 filtration Methods 0.000 abstract description 5
- 238000000956 solid--liquid extraction Methods 0.000 abstract description 3
- 230000007062 hydrolysis Effects 0.000 abstract description 2
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 2
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 abstract 1
- 239000012452 mother liquor Substances 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- IIASCQBFNHWZBE-UHFFFAOYSA-N 1-bromoethyl acetate Chemical compound CC(Br)OC(C)=O IIASCQBFNHWZBE-UHFFFAOYSA-N 0.000 description 3
- KEJCWVGMRLCZQQ-YJBYXUATSA-N Cefuroxime axetil Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-YJBYXUATSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229960002620 cefuroxime axetil Drugs 0.000 description 3
- 231100000024 genotoxic Toxicity 0.000 description 3
- 230000001738 genotoxic effect Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- G01N30/62—Detectors specially adapted therefor
- G01N30/72—Mass spectrometers
-
- 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
- G01N30/86—Signal analysis
- G01N30/8624—Detection of slopes or peaks; baseline correction
- G01N30/8631—Peaks
- G01N30/8634—Peak quality criteria
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Quality & Reliability (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention belongs to the technical field of analysis and detection, and particularly relates to an analysis method for bromoethyl acetate content in cephalosporin drugs. The analysis method utilizes a triple quaternary-gas chromatograph-mass spectrometer to measure the content of bromoethyl acetate in cefuroxime medicines, takes bromoethyl acetate as a reference substance, takes normal hexane as a solvent, and analyzes the content of bromoethyl acetate by a standard curve method. The analysis method of the invention overcomes the problems of active acetyl bromide, easy hydrolysis and difficult determination by a direct sample injection mode after solid-liquid extraction and filtration, and the detection method is efficient and accurate.
Description
Technical Field
The invention belongs to the technical field of analysis and detection, and particularly relates to an analysis method for bromoethyl acetate content in cephalosporin drugs.
Background
Cefuroxime is a second generation cephalosporin and has strong fat solubility. The cefuroxime can be hydrolyzed and released in the patient's body by oral administration to the patient. Cefuroxime has good antibacterial effect, and can be used for treating mild and moderate respiratory tract infection, skin soft tissue infection, genitourinary system infection and gonorrhea caused by sensitive bacteria. At present, some cefuroxime medicines use solvents such as 1-acetoxy-1-bromoethane, ethyl acetate and the like in the synthesis process, and bromoethyl acetate genotoxic impurities can be generated in the reaction and decomposition process, so that the medication safety is influenced.
For example, the preparation method of cefuroxime axetil disclosed in patent CN103435632a comprises the steps of completely dissolving cefuroxime axetil with dimethylformamide, and carrying out esterification reaction with 1-bromoethyl acetate under the catalysis of cupric chloride; hydrolyzing with ethyl acetate and sodium chloride solution, extracting, distilling under reduced pressure, crystallizing with cyclohexane, vacuum filtering, and drying to obtain high-purity cefuroxime axetil. In the preparation process, bromoethyl acetate genotoxic impurities are generated, so that the bromoethyl acetate genotoxic impurities contained in cefuroxime medicines need to be analyzed and detected.
However, bromoethyl acetate belongs to a high-activity substance, is severely decomposed by water and alcohol, can react with nucleophilic substances rapidly, and adopts a liquid method to carry out derivatization or decomposition and destruction on the bromoethyl acetate before indirect measurement, so that the test method is complicated and can influence the test accuracy, and a new test method needs to be researched.
Disclosure of Invention
The purpose of the invention is that: the method for analyzing the bromoethyl acetate content in the cephalosporin medicine is characterized in that a solvent which does not react with the bromoethyl acetate is selected for solid-liquid extraction and then is measured after filtration, so that the problems of extremely active bromoethyl acetate, easiness in hydrolysis and difficulty in measurement are solved, and the detection method is efficient and accurate.
According to the analysis method of the bromoethyl acetate content in the cefuroxime drug, the ternary quaternary-gas chromatograph-mass spectrometer is used for measuring the bromoethyl acetate content in the cefuroxime drug, the bromoethyl acetate is used as a reference substance, the normal hexane is used as a solvent, and the bromoethyl acetate content in the cefuroxime drug is analyzed by a standard curve method.
Specifically, the analysis method of bromoethyl acetate content in cefuroxime drug comprises the following steps:
(1) Setting the parameter conditions of liquid chromatography and mass spectrum of a triple quaternary-gas chromatograph-mass spectrometer;
(2) Placing the prepared reference substance solution and the prepared sample solution into a liquid phase small bottle, adopting direct sample injection, collecting data, and then carrying out analysis and test;
(3) And after the analysis is finished, calculating the concentration of bromoethyl acetate in the solution according to the peak area of bromoethyl acetate measured in the solution of the sample to be measured by using a standard curve, and carrying out quantitative analysis.
The parameter conditions of the gas chromatography are as follows:
the sample injection mode is direct sample injection;
the sample injection amount is 2 μl;
the chromatographic column is SH-Stabilwax-MS chromatographic column, 30m×0.25mm×0.25 μm;
the carrier gas is helium;
carrier gas flow rate 1.0ml/min, split ratio 3:1;
the temperature of the sample inlet is 200 ℃;
the temperature-raising program is as follows: the initial column temperature was 50℃for 3min, and the temperature was raised to 150℃at a rate of 12℃per minute, and then to 250℃at a rate of 40℃per minute for 2min.
The parameter conditions of the mass spectrum are as follows:
adopting an EI ion source, wherein collision gas is argon;
delaying the solvent for 6.0min, and collecting the solvent for 6.0-8.5 min;
in the MRM scanning mode, the quantitative ion pair is 87.05>43.05, and the qualitative ion pair is 106.95>27.05;
the ion source temperature is 230 ℃ and the interface temperature is 220 ℃.
The standard curve is prepared by preparing linear standard solutions, sequentially injecting the linear standard solutions into a gas chromatograph-mass spectrometer, and making a standard curve according to the concentration of each linear solution and the peak area.
As a preferred embodiment, the standard curve can be prepared by the following method:
(1) Taking 90mg of bromoethyl acetate, precisely weighing, placing into a 100ml measuring flask, dissolving with n-hexane, diluting to a scale, and shaking uniformly to obtain a reference mother liquor with the concentration of 0.9 mg/ml;
precisely measuring a proper amount of reference substance mother liquor of 0.9mg/ml, placing the reference substance mother liquor into a 100ml measuring flask, diluting to a scale with n-hexane, and shaking uniformly to prepare 900ng/ml reference substance stock solution;
(2) Accurately measuring 900ng/ml of control stock solution, and diluting with n-hexane to obtain linear solutions with concentrations of 18ng/ml, 27ng/ml, 45ng/ml, 90ng/ml, 135ng/ml and 180 ng/ml;
(3) Setting parameter conditions of gas chromatography and mass spectrum, then analyzing the linear solutions in turn, and making a standard curve according to the concentration of each linear solution to the peak area.
The standard curve equation for bromoethyl acetate is as follows:
Y＝4563.21X-21783.66，r＝0.9999。
the preparation method of the sample solution comprises the following steps: 300mg of cefuroxime drug is taken, precisely weighed, placed in a 5ml measuring flask, diluted to a scale by normal hexane, and subjected to vortex oscillation for 1min and then filtered through a 0.22 mu m filter membrane, thus obtaining the sample solution.
Placing the prepared sample solution into a liquid phase small bottle, adopting direct sample injection, collecting data, calculating the concentration of bromoethyl acetate in the solution according to the measured peak area of bromoethyl acetate, and analyzing the content of bromoethyl acetate by a standard curve method.
Compared with the prior art, the invention has the following advantages:
(1) The detection and analysis method of the invention uses normal hexane as a solvent, adopts a direct sample injection method after solid-liquid extraction and filtration, has short reaction time and simple operation, solves the problems that bromoethyl acetate has active properties and can not be directly measured, and has accurate quantification;
(2) The detection and analysis method has the advantages of light pollution of the chromatographic column and the ion source of the mass spectrum detector, and relatively simple maintenance work.
Drawings
FIG. 1 is a standard graph of bromoethyl acetate;
FIG. 2 is a total ion flow diagram of the labeling solution-1 under the precision term of example 2.
Detailed Description
The present invention will be described in detail with reference to specific examples.
The instrumentation used in the examples is as follows:
triple quaternary-gas chromatograph-mass spectrometer: GC model 2030, MS model TQ-8050NX.
The reagents, solutions used in the examples were as follows:
0.9mg/ml bromoethyl acetate control mother liquor prepared by taking normal hexane as a solvent.
The analytical conditions parameters in the examples are as follows:
the parameters of the liquid chromatograph were: the sample injection mode is direct sample injection; the sample injection amount is 2 μl; the chromatographic column filler is polyethylene glycol with the specification of 30m multiplied by 0.25mm multiplied by 0.25 mu m; the carrier gas is helium; carrier gas flow rate 1.0ml/min, split ratio 3:1; the temperature of the sample inlet is 200 ℃; the temperature-raising program is as follows: the initial column temperature was 50℃for 3min, and the temperature was raised to 150℃at a rate of 12℃per minute, and then to 250℃at a rate of 40℃per minute for 2min.
The parameter conditions of the mass spectrum are as follows: adopting an EI ion source, wherein collision gas is argon; delaying the solvent for 6.0min, and collecting the solvent for 6.0-8.5 min; in the MRM scanning mode, the quantitative ion pair is 87.05>43.05, and the qualitative ion pair is 106.95>27.05; the ion source temperature is 230 ℃ and the interface temperature is 220 ℃.
Example 1
Linear and linear range analysis:
the method comprises the following steps:
precisely measuring 100 mu l of bromoethyl acetate reference substance mother liquor with the concentration of 0.9mg/ml, placing the mother liquor in a 100ml volumetric flask, and diluting the mother liquor to a scale with n-hexane to obtain reference substance stock solution with the concentration of 900 ng/ml; precisely measuring a proper amount of stock solution, and diluting with n-hexane to obtain linear solutions with concentrations of 18ng/ml, 27ng/ml, 45ng/ml, 90ng/ml, 135ng/ml and 180 ng/ml; and (3) sample injection detection, then sequentially analyzing the linear solutions, and respectively making regression curves according to the concentration of each linear solution and the peak area.
Discussion of results:
bromoethyl acetate standard curve as shown in fig. 1, y= 4563.21X-21783.66, r=0.9999; the linear relation is formed between the concentrations of 18ng/ml to 180ng/ml (corresponding to the limit concentration of 20% -200%), and the linear correlation coefficient r=0.9999.
Example 2
Precision analysis:
the method comprises the following steps:
precisely weighing 250 μl of reference substance mother liquor of 0.9mg/ml, placing in a 10ml volumetric flask, diluting to scale with n-hexane, and shaking to obtain bromoethyl acetate intermediate solution with concentration of 22.5 μg/ml;
300mg of the sample is taken, precisely weighed, placed in a 5ml volumetric flask, added with 20 mu l of intermediate solution of bromoethyl acetate with the concentration of 22.5 mu g/ml, diluted to a scale by normal hexane, vortex-vibrated for 1min and filtered to obtain the sample adding standard solution with the standard concentration of 90ng/ml, and 6 parts are prepared by the same method.
Discussion of results:
the results of precision investigation of bromoethyl acetate are shown in Table 1.
Table 1 results of precision investigation
Example 3
Accuracy analysis:
the method comprises the following steps:
(1) Test solution: 300mg of the product is taken, precisely weighed, placed in a 5ml volumetric flask, diluted to a scale with normal hexane, vortex-oscillated for 1min and filtered to obtain the sample solution with the concentration of 60 mg/ml. 3 parts were prepared.
(2) 50% of test sample adding standard solution: 300mg of the product is taken, precisely weighed, placed in a 5ml volumetric flask, added with 10 mu l of intermediate solution of bromoethyl acetate with the concentration of 22.5 mu g/ml, diluted to a scale by normal hexane, vortex-vibrated for 1min and filtered to obtain the sample adding standard solution with the standard concentration of 45 ng/ml. 3 parts of the mixture are prepared by the same method.
(3) 100% of test sample adding standard solution: 300mg of the product is taken, precisely weighed, placed in a 5ml volumetric flask, added with 20 mu l of intermediate solution of bromoethyl acetate with the concentration of 22.5 mu g/ml, diluted to a scale by normal hexane, vortex-vibrated for 1min and filtered to obtain the sample adding standard solution with the standard concentration of 90 ng/ml. 6 parts of the mixture were prepared in the same manner.
(4) 150% of test sample adding standard solution: 300mg of the product is taken, precisely weighed, placed in a 5ml volumetric flask, added with 30 mu l of intermediate solution of bromoethyl acetate with the concentration of 22.5 mu g/ml, diluted to a scale by normal hexane, vortex-vibrated for 1min and filtered to obtain the test sample adding standard solution with the standard concentration of 135 ng/ml. 3 parts of the mixture are prepared by the same method.
Discussion of results:
the accuracy analysis results of bromoethyl acetate are shown in table 2, respectively.
TABLE 2 accuracy analysis results
Example 4
And (3) detection limit analysis:
the method comprises the following steps:
taking 0.1ml of control stock solution with the concentration of 900ng/ml, adding 8.9ml of normal hexane for dilution, and shaking uniformly to obtain the detection limit solution with the concentration of 10 ng/ml. 3 needles were collected continuously.
Discussion of results:
the detection limit analysis results of bromoethyl acetate are shown in Table 3.
TABLE 3 detection limit analysis results
Example 5
Analysis of test article:
the method comprises the following steps:
respectively taking 300mg of test samples in different batches, precisely weighing, placing in a 5ml volumetric flask, diluting to a scale with n-hexane, vortex oscillating for 1min, and filtering to obtain a test sample solution with the concentration of 60 mg/ml; placing the prepared sample solution into a liquid phase small bottle, adopting direct sample injection, collecting data, calculating the concentration of bromoethyl acetate in the solution according to the measured peak area of bromoethyl acetate, and analyzing the content of bromoethyl acetate by a standard curve method.
The calculation formula is as follows: 1-bromoethyl acetate content (ng/mg) =c×v/m;
wherein: c is the concentration (ng/ml) obtained by standard curve calculation, V is the volume (ml) of the solvent used for dissolving the test sample, and m is the mass (mg) of the second-generation cephalosporin cefuroxime medicines.
Discussion of results:
the results of analysis of the bromoethyl acetate content in the test samples of the different batches are shown in Table 4.
TABLE 4 analysis results of bromoethyl acetate content in test samples
The analysis method is used for detecting the bromoethyl acetate content in the second-generation cephalosporin cefuroxime medicines, overcomes the difficulties of active property and difficult detection of bromoethyl acetate, and has the advantages of good precision, high accuracy, low detection limit, detection time saving and high efficiency and accuracy.
Claims (9)
1. A method for analyzing bromoethyl acetate content in cephalosporin drugs is characterized in that: and determining the content of bromoethyl acetate in the cefuroxime medicines by using a triple quaternary-gas chromatograph-mass spectrometer, taking bromoethyl acetate as a reference substance, taking normal hexane as a solvent, and analyzing the content of bromoethyl acetate in the cefuroxime medicines by using a standard curve method.
2. The method for analyzing the bromoethyl acetate content in the cephalosporin according to claim 1, which is characterized in that: the method comprises the following steps:
(1) Setting the parameter conditions of gas chromatography and mass spectrum of a triple quaternary-gas chromatograph-mass spectrometer;
(2) Placing the prepared reference substance solution and the prepared sample solution into a liquid phase small bottle, adopting direct sample injection, collecting data, and then carrying out analysis and test;
(3) And after the analysis is finished, calculating the concentration of bromoethyl acetate in the solution according to the peak area of bromoethyl acetate measured in the solution of the sample to be measured by using a standard curve, and carrying out quantitative analysis.
3. The method for analyzing the bromoethyl acetate content in the cephalosporin according to claim 1 or 2, characterized in that: the gas chromatograph parameters of the triple quaternary-gas chromatograph-mass spectrometer are as follows:
the sample injection mode is direct sample injection;
the sample injection amount is 2 μl;
the chromatographic column filler is polyethylene glycol with the specification of 30m multiplied by 0.25mm multiplied by 0.25 mu m;
the carrier gas is helium;
carrier gas flow rate 1.0ml/min, split ratio 3:1;
the temperature of the sample inlet is 200 ℃;
the temperature-raising program is as follows: the initial column temperature was 50℃for 3min, and the temperature was raised to 150℃at a rate of 12℃per minute, and then to 250℃at a rate of 40℃per minute for 2min.
4. The method for analyzing the bromoethyl acetate content in the cephalosporin according to claim 1 or 2, characterized in that: the parameters of the mass spectrum of the triple quaternary-gas chromatograph-mass spectrometer are as follows:
adopting an EI ion source, wherein collision gas is argon;
delaying the solvent for 6.0min, and collecting the solvent for 6.0-8.5 min;
in the MRM scanning mode, the quantitative ion pair is 87.05>43.05, and the qualitative ion pair is 106.95>27.05;
the ion source temperature is 230 ℃ and the interface temperature is 220 ℃.
5. The method for analyzing the bromoethyl acetate content in the cephalosporin according to claim 2, which is characterized in that: the standard curve is prepared by preparing linear standard solutions, sequentially injecting the linear standard solutions into a gas chromatograph-mass spectrometer, and making a standard curve according to the concentration of each linear solution and the peak area.
6. The method for analyzing bromoethyl acetate content in cephalosporins according to claim 5, characterized in that: the standard curve is prepared by the following method:
(1) Preparing a bromoethyl acetate reference stock solution with the concentration of 900ng/ml by taking n-hexane as a n-hexane-dissolving agent;
(2) Accurately measuring 900ng/ml of control stock solution, and diluting with n-hexane to obtain linear solutions with concentrations of 18ng/ml, 27ng/ml, 45ng/ml, 90ng/ml, 135ng/ml and 180 ng/ml;
(3) Setting parameter conditions of gas chromatography and mass spectrum, then analyzing the linear solutions in turn, and making a standard curve according to the concentration of each linear solution to the peak area.
7. The method for analyzing bromoethyl acetate content in cephalosporins according to claim 2, 5 or 6, characterized in that: the standard curve equation for bromoethyl acetate is as follows:
Y＝4563.21X-21783.66，r＝0.9999。
8. the method for analyzing the bromoethyl acetate content in the cephalosporin according to claim 2, which is characterized in that: the preparation method of the sample solution comprises the following steps: 300mg of cefuroxime drug is taken, precisely weighed, placed in a 5ml measuring flask, diluted to a scale by normal hexane, and subjected to vortex oscillation for 1min and then filtered through a 0.22 mu m filter membrane, thus obtaining the sample solution.
9. The method for analyzing the bromoethyl acetate content in the cephalosporin according to claim 8, which is characterized in that: placing the prepared sample solution into a liquid phase small bottle, adopting direct sample injection, collecting data, calculating the concentration of bromoethyl acetate in the solution according to the measured peak area of bromoethyl acetate, and analyzing the content of bromoethyl acetate by a standard curve method.
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