CN117471012A - Method for detecting related substances of p-chlorobenzoyl chloride by gas chromatography - Google Patents
Method for detecting related substances of p-chlorobenzoyl chloride by gas chromatography Download PDFInfo
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- CN117471012A CN117471012A CN202311425656.3A CN202311425656A CN117471012A CN 117471012 A CN117471012 A CN 117471012A CN 202311425656 A CN202311425656 A CN 202311425656A CN 117471012 A CN117471012 A CN 117471012A
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- chlorobenzoyl chloride
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- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 239000000126 substance Substances 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000004817 gas chromatography Methods 0.000 title claims abstract description 22
- 238000001514 detection method Methods 0.000 claims abstract description 18
- 238000002347 injection Methods 0.000 claims abstract description 17
- 239000007924 injection Substances 0.000 claims abstract description 17
- 239000007789 gas Substances 0.000 claims abstract description 11
- 239000012159 carrier gas Substances 0.000 claims abstract description 10
- 239000000523 sample Substances 0.000 claims description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- 239000012535 impurity Substances 0.000 claims description 21
- 239000000243 solution Substances 0.000 claims description 20
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 claims description 10
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 claims description 8
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000012488 sample solution Substances 0.000 claims description 7
- CEOCVKWBUWKBKA-UHFFFAOYSA-N 2,4-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1Cl CEOCVKWBUWKBKA-UHFFFAOYSA-N 0.000 claims description 6
- VTXNOVCTHUBABW-UHFFFAOYSA-N 3,4-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C(Cl)=C1 VTXNOVCTHUBABW-UHFFFAOYSA-N 0.000 claims description 6
- 239000011550 stock solution Substances 0.000 claims description 6
- 239000012085 test solution Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 3
- 239000013558 reference substance Substances 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 230000000630 rising effect Effects 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 230000035945 sensitivity Effects 0.000 abstract description 5
- 239000010453 quartz Substances 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 5
- 239000012490 blank solution Substances 0.000 description 4
- 125000003963 dichloro group Chemical group Cl* 0.000 description 4
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000011895 specific detection Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009876 antimalignant effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- -1 methyl ester compound Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- 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
- G01N30/60—Construction of the column
- G01N30/6052—Construction of the column body
-
- 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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- Physics & Mathematics (AREA)
- 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)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention relates to the technical field of chemical industry detection, in particular to a method for detecting substances related to p-chlorobenzoyl chloride by using a gas chromatography, wherein an instrument is a gas chromatograph, a detector is an FID detector, a chromatographic column adopts a MEGA-1 quartz capillary chromatographic column, carrier gas is N2, the flow rate is 2.0mL/min, the split ratio is 20:1, and the temperature programming is carried out: the starting temperature was 130℃for 15 minutes and the temperature was raised to 200℃at a rate of 15℃per minute for 5 minutes. Sample injection mode: directly injecting sample, wherein the temperature of an injection port is 260 ℃ and the temperature of a detector is 280 ℃; sample injection volume: the method has the advantages of simple operation, strong specificity, high sensitivity and accuracy, good linearity and capability of accurately and rapidly measuring the content of various related substances in the p-chlorobenzoyl chloride.
Description
Technical Field
The invention relates to the technical field of chemical detection, in particular to a method for detecting substances related to p-chlorobenzoyl chloride by using a gas chromatography.
Background
P-chlorobenzoyl chloride is an important starting material in the synthesis of methotrexate drug substances. Methotrexate is an immunosuppressant which is used for treating children leukemia since the discovery of the 40 th century, is used for treating psoriasis since the 50 th century, is a clinically commonly used anti-malignant tumor medicament at present, and is mainly applicable to diseases such as acute leukemia, breast cancer, chorionic epithelial cancer, malignant grape embryo and the like. The main dosage forms include tablets, injection and oral liquid, and are incorporated into the national medical insurance catalogue. Therefore, it is particularly important to control the quality of the starting materials at the source.
The existing detection methods of substances related to the p-chlorobenzoyl chloride include high performance liquid chromatography and gas chromatography. Since acyl chloride impurities are unstable and have high activity, chen Fengqin et al use high performance liquid chromatography to hydrolyze p-chlorobenzoyl chloride to p-chlorobenzoic acid and then analyze isomer impurities; wang Shijin et al invent a liquid phase detection method of p-chlorobenzoyl chloride by reacting an acyl chloride compound with an excessive amount of anhydrous methanol to detect the generated methyl ester compound, thereby achieving the purpose of detecting and controlling isomers, and the reproducibility is poor due to the fact that the mobile phase contains water and is easy to hydrolyze into acid. Jin Qian by gas chromatography, esterifying p-chlorobenzoyl chloride with methanol, and detecting the esterified isomer impurity; the derivatization method has high temperature and time requirements, and is complex to operate and poor in reproducibility.
In the prior art, no method for directly detecting the position isomer and the dichloro isomer impurity in the p-chlorobenzoyl chloride exists, so that the development of a detection method capable of effectively detecting the isomer impurity and the dichloro isomer impurity in the p-chlorobenzoyl chloride is necessary. At present, a very simple and effective detection method is needed to be provided for enterprise central control and finished product detection.
Disclosure of Invention
The invention aims to provide a method for detecting related substances of p-chlorobenzoyl chloride by using a gas chromatography, which has the characteristics of simple operation and capability of effectively detecting isomer impurities and dichloro isomer impurities in the p-chlorobenzoyl chloride.
The technical aim of the invention is realized by the following technical scheme:
a method for detecting p-chlorobenzoyl chloride related substances by gas chromatography, comprising the following steps:
1) Selection of the device: adopting a gas chromatograph, an FID detector, wherein the chromatographic column is MEGA-1 or a capillary column with similar polarity;
2) Preparation of a System applicability solution: about 0.1g of o-chlorobenzoyl chloride, about 0.17g of m-chlorobenzoyl chloride and about 0.1g of benzoyl chloride are respectively taken, and are precisely weighed, put into a 20ml measuring flask, dissolved and diluted to scale by acetone, and uniformly shaken to be used as an impurity mixed stock solution; about 0.5g of p-chlorobenzoyl chloride is taken, precisely weighed, placed into a 10ml measuring flask, added with acetone for dissolution, precisely added with 0.3ml of impurity reference substance stock solution, diluted to scale with acetone, and shaken uniformly;
3) Preparation of test solution: weighing 0.5g of the sample to be tested, placing the sample into a 10ml volumetric flask, adding acetone to dilute the sample to a scale, and shaking the sample uniformly;
4) Preparation of control solution: precisely measuring the sample solution of 0.5ml to 100ml in a measuring flask, adding acetone to dilute to a scale, and shaking uniformly;
5) Determination of the substance: and precisely measuring 0.2 mu l of each of the system applicability solution, the control solution and the sample solution, respectively injecting into a gas chromatograph, recording a chromatogram, and calculating according to the self-control method and the peak area.
Preferably, the chromatographic column selected in the step 1) is a MEGA-1 capillary column.
Preferably, the column temperature change flow in the gas phase detection is as follows: the initial temperature of the column is 125-135 ℃, the holding time is 13-17min, then the temperature is increased to 200 ℃ at the temperature rising rate of 13-17 ℃/min, and the final temperature of the column is 3-7min.
Preferably, the carrier gas in the gas chromatography detection is nitrogen.
Preferably, the temperature of the sample inlet in the gas chromatography detection is 250-270 ℃, and the temperature of the FID detector is 270-290 ℃.
Preferably, the sample injection mode in the gas chromatography detection is direct sample injection, and the sample injection volume is 0.2 mu L.
Preferably, the carrier gas flow rate is 1.5-2.5ml/min and the split ratio is 20:1.
Preferably, the substance measured in the substance measurement step includes at least one or a combination of two or more of benzoyl chloride, m-chlorobenzoyl chloride, p-chlorobenzoyl chloride, o-chlorobenzoyl chloride, 2, 4-dichlorobenzoyl chloride and 3, 4-dichlorobenzoyl chloride.
In summary, the invention has the following beneficial effects:
the method can effectively separate related substances in the p-chlorobenzoyl chloride, such as benzoyl chloride, m-chlorobenzoyl chloride, o-chlorobenzoyl chloride, 2, 4-dichlorobenzoyl chloride, 3, 4-dichlorobenzoyl chloride and the like, and the method has the advantages of simple operation, strong specificity, high sensitivity, high accuracy, good linearity and controllable quality of the p-chlorobenzoyl chloride because the intermediate chlorobenzoyl chloride, the p-chlorobenzoyl chloride, the o-chlorobenzoyl chloride and the like are all isomers and various dichloro impurities such as the 2, 4-dichlorobenzoyl chloride, the 3, 4-dichlorobenzoyl chloride and the like are all isomers, and the acyl chloride impurities are unstable and have high activity and are easy to hydrolyze into corresponding acid, so that the detection method is unstable; the invention provides a stable and reliable detection method for detecting substances related to the p-chlorobenzoyl chloride.
Drawings
FIG. 1 is a blank solution chromatogram;
FIG. 2 is a chromatogram of a system mixed solution;
FIG. 3 is a chromatogram of a test solution;
FIG. 4 is a chromatogram of a control solution;
FIG. 5 is a graph showing the results of linear tests of various related substances;
FIG. 6 is a chromatogram of an accurate solution.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings.
The present embodiment is only for explanation of the present invention and is not to be construed as limiting the present invention, and modifications to the present embodiment, which may not creatively contribute to the present invention as required by those skilled in the art after reading the present specification, are all protected by patent laws within the scope of claims of the present invention.
Examples:
the instrumentation and chromatographic conditions used in the following examples are as follows: the gas chromatograph is Agilent7890A, a FID detector is adopted, the initial temperature of the column is 125-135 ℃, the holding time is 13-17min, then the temperature is increased to 200 ℃ at the heating rate of 13-17 ℃/min, and the final temperature of the column is 3-7min; the carrier gas is nitrogen, preferably, the flow rate of the carrier gas is 1.5-2.5ml/min, and the split ratio is 20:1; the temperature of the sample inlet is 250-270 ℃, and the temperature of the detector is 270-290 ℃; the sample injection mode is direct sample injection; the sample volume was 0.2. Mu.L.
A method for detecting p-chlorobenzoyl chloride related substances by gas chromatography, comprising the following steps:
1) Selection of instrument and chromatographic conditions: a gas chromatograph; the chromatographic column is MEGA-1 (50 m×0.32mm×1.0 μm) or capillary chromatographic column with similar polarity; adopting an FID detector, wherein the initial temperature of the column is 125-135 ℃, the holding time is 13-17min, then the temperature is increased to 200 ℃ at the heating rate of 13-17 ℃/min, and the holding time of the final temperature of the column is 3-7min; the carrier gas is nitrogen.
In order to achieve a better detection effect, the flow rate of the carrier gas is 1.5-2.5ml/min, and the split ratio is 20:1; the temperature of the sample inlet is 250-270 ℃, and the temperature of the detector is 270-290 ℃; the sample injection mode is direct sample injection; the sample volume was 0.2. Mu.L.
2) Preparing a solution, and preparing the following solutions:
a. blank solution (diluent): acetone;
b. system applicability solution configuration: about 0.1g of o-chlorobenzoyl chloride, about 0.17g of m-chlorobenzoyl chloride and about 0.1g of benzoyl chloride are respectively taken, and are precisely weighed, put into a 20ml measuring flask, dissolved and diluted to scale by acetone, and uniformly shaken to be used as an impurity mixed stock solution; about 0.5g of p-chlorobenzoyl chloride is taken, precisely weighed, placed into a 10ml measuring flask, added with acetone for dissolution, precisely added with 0.3ml of impurity reference substance stock solution, diluted to scale with acetone, and shaken uniformly;
c. sample solution preparation: weighing 0.5g of the sample to be tested, placing the sample into a 10ml volumetric flask, adding acetone to dilute the sample to a scale, shaking the sample uniformly, and preparing the sample again when in use;
d. control solution preparation: accurately measuring the sample solution from 0.5ml to 100ml in a measuring flask, adding acetone to dilute to a scale, and shaking uniformly.
Sampling according to the following sequence table:
| name of the name | Number of sample injection needles |
| Blank solution | 1 or more needle |
| System applicability solution | 1 needle |
| Control solution | 1 needle |
| Test solution | 1 needle |
The peak area of each related substance in the p-chlorobenzoyl chloride test sample solution is calculated according to a self-control method.
Preferably, the chromatographic conditions selected for the gas chromatographic analysis according to the invention are as follows:
using a FID detector;
chromatographic column: MEGA-1 (50 m. Times.0.32 mm. Times.1.0 μm) or capillary chromatographic columns of similar polarity;
programming temperature: the initial temperature was 1300℃for 15 minutes and the temperature was raised to 200℃per minute for 5 minutes. Carrier gas: nitrogen gas flow rate of 2.0mL/min, split ratio: 20:1;
sample inlet temperature: 260 ℃; detector (FID) temperature: 280 ℃;
sample injection mode: directly sampling; sample injection volume: 0.2 μl.
The specificity is examined, and the examination results are shown in fig. 1-2:
precisely measuring the blank solution, mixing the solution with the system, the solution to be tested and the positioning solution of each impurity by 0.2 mu L, injecting into a gas chromatograph, and recording the chromatograms. The experimental results of the positioning and the separation degree of each impurity show that the blank has no interference, other related substances have no interference on the measurement of the sample, the minimum separation degree between the impurities is 1.9, the specificity of the analysis condition is good, and the test result is as follows:
results of the proprietary test
Sensitivity test investigation results:
the specific detection results of the limit of quantification (LOQ) are as follows:
the specific detection Limit (LOD) results are as follows:
the quantitative limit and detection limit measurement results of each known impurity and the main component show that: the detection sensitivity of each impurity is high, and the method sensitivity meets the requirements.
Linearity investigation, as shown in fig. 4:
the peak area is plotted against the concentration, benzoyl chloride is in the range of 29.242 mug/mL-292.421 mug/mL, m-chlorobenzoyl chloride is in the range of 30.066 mug/mL-300.656 mug/mL, p-chlorobenzoyl chloride is in the range of 51.030 mug/mL-510.298 mug/mL, o-chlorobenzoyl chloride is in the range of 30.967 mug/mL-309.672 mug/mL, 2, 4-dichlorobenzoyl chloride is in the range of 49.788 mug/mL-497.875 mug/mL, 3, 4-dichlorobenzoyl chloride is in the range of 51.508 mug/mL-515.075 mug/mL, the sample concentration is in a linear relationship with the peak area, and the specific results are as follows:
accuracy inspection, chromatogram is shown in fig. 5:
preparing recovery rate solutions according to the limit concentration of benzoyl chloride, m-chlorobenzoyl chloride, o-chlorobenzoyl chloride, 2, 4-dichlorobenzoyl chloride and 3, 4-dichlorobenzoyl chloride of 20%, 100% and 200% by sample addition, preparing 3 parts of each group of concentration in parallel, preparing one part of test solution and one part of reference solution, and calculating the recovery rate according to the chromatographic condition. The recovery rate of each related substance is in the range of 80% -120%, and the results are shown in the following table:
while the invention has been described with respect to the preferred embodiments thereof, it will be understood by those skilled in the art that various modifications may be made without departing from the principles of the invention, and such modifications should also be considered as being within the scope of the invention and not as being particularly limited thereto.
Claims (8)
1. A method for detecting p-chlorobenzoyl chloride related substances by gas chromatography, comprising the steps of:
1) Selection of the device: adopting a gas chromatograph, an F ID detector and a chromatographic column which is MEGA-1 or a capillary column with similar polarity;
2) Preparation of a System applicability solution: about 0.1g of o-chlorobenzoyl chloride, about 0.17g of m-chlorobenzoyl chloride and about 0.1g of benzoyl chloride are respectively taken, and are precisely weighed, put into a 20m l measuring flask, dissolved and diluted to scale by acetone, and uniformly shaken to be used as an impurity mixed stock solution; about 0.5g of p-chlorobenzoyl chloride is taken, precisely weighed, placed into a 10ml measuring flask, added with acetone for dissolution, precisely added with 0.3ml of impurity reference substance stock solution, diluted to scale with acetone, and shaken uniformly;
3) Preparation of test solution: weighing 0.5g of the sample to be tested, placing the sample into a 10ml volumetric flask, adding acetone to dilute the sample to a scale, and shaking the sample uniformly;
4) Preparation of control solution: precisely measuring the sample solution of 0.5ml to 100ml in a measuring flask, adding acetone to dilute to a scale, and shaking uniformly;
5) Determination of the substance: and precisely measuring 0.2 mu l of each of the system applicability solution, the control solution and the sample solution, respectively injecting into a gas chromatograph, recording a chromatogram, and calculating according to the self-control method and the peak area.
2. The method for detecting p-chlorobenzoyl chloride related substances by gas chromatography according to claim 1, wherein the chromatographic column selected in step 1) is a MEGA-1 capillary column.
3. The method for detecting p-chlorobenzoyl chloride related substances by gas chromatography according to claim 1, wherein the column temperature change flow in the gas phase detection is as follows: the initial temperature of the column is 125-135 ℃, the holding time is 13-17min, then the temperature is increased to 200 ℃ at the temperature rising rate of 13-17 ℃/min, and the final temperature of the column is 3-7min.
4. The method for detecting p-chlorobenzoyl chloride related substances by gas chromatography according to claim 1, wherein the carrier gas in the gas chromatography is nitrogen.
5. The method for detecting p-chlorobenzoyl chloride related substances by gas chromatography according to claim 1, wherein the sample inlet temperature is 250-270 ℃ and the FID detector temperature is 270-290 ℃.
6. The method for detecting substances related to p-chlorobenzoyl chloride by using the gas chromatography according to claim 1, wherein the sample injection mode in the gas chromatography detection is direct sample injection, and the sample injection volume is 0.2 mu L.
7. The method for detecting p-chlorobenzoyl chloride related substances by gas chromatography according to claim 1, wherein the carrier gas flow rate is 1.5-2.5ml/min and the split ratio is 20:1.
8. The method for detecting p-chlorobenzoyl chloride related substances by gas chromatography according to claim 1, wherein the substances detected in the substance detecting step include at least one or a combination of two or more of benzoyl chloride, m-chlorobenzoyl chloride, p-chlorobenzoyl chloride, o-chlorobenzoyl chloride, 2, 4-dichlorobenzoyl chloride and 3, 4-dichlorobenzoyl chloride.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311425656.3A CN117471012A (en) | 2023-10-31 | 2023-10-31 | Method for detecting related substances of p-chlorobenzoyl chloride by gas chromatography |
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| CN202311425656.3A CN117471012A (en) | 2023-10-31 | 2023-10-31 | Method for detecting related substances of p-chlorobenzoyl chloride by gas chromatography |
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| CN202311425656.3A Withdrawn CN117471012A (en) | 2023-10-31 | 2023-10-31 | Method for detecting related substances of p-chlorobenzoyl chloride by gas chromatography |
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