CN113671077B - Method for detecting acryloyl chloride and related substances - Google Patents
Method for detecting acryloyl chloride and related substances Download PDFInfo
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- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 28
- 239000000126 substance Substances 0.000 title claims abstract description 23
- 238000001514 detection method Methods 0.000 claims abstract description 27
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000001212 derivatisation Methods 0.000 claims abstract description 10
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- 239000012071 phase Substances 0.000 claims description 13
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- 238000010828 elution Methods 0.000 claims description 10
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 8
- 239000012346 acetyl chloride Substances 0.000 claims description 8
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 36
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 abstract description 12
- 238000004811 liquid chromatography Methods 0.000 abstract description 7
- 230000035945 sensitivity Effects 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 2
- 239000000523 sample Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000011550 stock solution Substances 0.000 description 9
- 238000010606 normalization Methods 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 239000013558 reference substance Substances 0.000 description 6
- 239000012488 sample solution Substances 0.000 description 6
- 238000007865 diluting Methods 0.000 description 5
- 238000004817 gas chromatography Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 150000001263 acyl chlorides Chemical class 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- -1 acrylic ester Chemical class 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 150000003335 secondary amines Chemical group 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012085 test solution Substances 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
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
- G01N30/8679—Target compound analysis, i.e. whereby a limited number of peaks is analysed
-
- 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
- G01N2030/067—Preparation by reaction, e.g. derivatising the sample
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pathology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- General Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Library & Information Science (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for detecting acryloyl chloride and related substances thereof, which uses aniline substances as a derivative reagent and uses high performance liquid chromatography for detection. At present, no report on the detection of the acryloyl chloride and/or related substances thereof by adopting liquid chromatography exists, and the method adopts N-ethylaniline as a derivatization reagent, so that the operation is simple and convenient, the derivatization time is short, the sensitivity is high, and the side reaction is less; the ultraviolet detector is used for detecting liquid chromatography, the application range is wide, known impurities and unknown impurities in a sample can be detected, and the repeatability and the durability are good.
Description
Technical Field
The invention belongs to the field of medicine analysis, and relates to an HPLC detection method for acryloyl chloride and related substances thereof.
Background
The acryloyl chloride is colorless flammable liquid, has corrosiveness and irritation and is easy to volatilize. Because of the active chemical property, various chemical reactions can occur, and various organic matters such as acrylic ester and acrylamide compounds are derived, so that the catalyst is an important raw material in the industries of medicine, chemical industry and the like.
The chemical nature of the acrylic acid chloride is active, and the acrylic acid chloride can react with water, alcohol and amine solvents, so that the content of the acrylic acid chloride is difficult to directly detect. At present, the method for detecting the content of the acryloyl chloride is mainly gas chromatography, namely, the acryloyl chloride is firstly derived by alcohol or amine (mainly aniline) compounds and then detected by gas chromatography, but the detection by gas chromatography can leak detection of some unknown impurities, and meanwhile, some unknown peaks in the gas chromatography cannot be judged to be solvent peaks or impurity peaks, and accurate quantification cannot be performed. At present, no detection method of substances related to the acryloyl chloride is reported.
HPLC is an important branch of chromatography, is a novel analysis technology developed on the basis of classical liquid chromatography and gas chromatography at the end of the 60 th century, adopts a high-pressure infusion system, pumps a mobile phase into a chromatographic column, elutes each component in the chromatographic column in an isocratic or gradient elution mode, and sequentially enters a detector (ultraviolet detector (UV), diode Array Detector (DAD) or Evaporative Light Scattering Detector (ELSD) and the like) for detection, thereby realizing analysis of samples and being widely applied to the fields of medicines, foods and the like. HPLC can be used for analyzing organic compounds with high boiling point, difficult volatilization, unstable heating, large molecular weight, different polarities, bioactive substances, high molecular compounds and the like, is suitable for 80% of organic compound analysis, makes up for the deficiency of GC, and simultaneously has the characteristics of high analysis efficiency, high selectivity, high detection sensitivity, high analysis speed and the like.
Disclosure of Invention
Based on the above problems, the present invention actually provides a method for detecting the acryloyl chloride and related substances by high performance liquid chromatography for the first time.
Specifically, the invention provides a method for detecting acryloyl chloride and/or related substances thereof, which uses aniline substances as a derivative reagent and uses high performance liquid chromatography for detection, and comprises the following detection conditions:
chromatographic column: octadecylsilane chemically bonded silica gel column
Mobile phase: the organic phase was acetonitrile: methanol (3-1): 1, aqueous phase pH2-4, gradient elution procedure comprising:
at present, no report on the detection of the acryloyl chloride and/or related substances thereof by adopting liquid chromatography exists, and the method adopts N-ethylaniline as a derivatization reagent, so that the operation is simple and convenient, the derivatization time is short, the sensitivity is high, and the side reaction is less; the ultraviolet detector is used for detecting liquid chromatography, the application range is wide, known impurities and unknown impurities in a sample can be detected, and the repeatability and the durability are good.
The related substances are selected from acetyl chloride, 3-chloropropionyl chloride and propionyl chloride.
Wherein the aniline is selected from aromatic secondary amines, such as N-ethylaniline.
Wherein, in the organic phase, acetonitrile: methanol may be selected from 3:1, 2:1, 1:1, etc.
Among them, common organic acids and/or inorganic acids are pH adjusters.
Wherein, the pH regulator can be selected from conventional acidic reagents such as hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid and the like. The pH may be greater than 2.8, such as 2.8-4, excluding 2.8, and may be further selected from 3.0-3.2.
Further, the gradient elution procedure for the first 26min was:
alternatively, the first 28min gradient elution procedure was:
the detection method of the invention further comprises one of the following conditions:
(1) Column temperature: 20-30 ℃; for example, 20, 23, 24, 25, 26, 27, 30℃and the like are used.
(2) Flow rate: 0.8-1.2 ml/min; for example, 0.8, 0.9, 1.0, 1.1, 1.2ml/min are used.
(3) Wavelength: 220.+ -.5 nm. For example, 215, 218, 219, 220, 221, 222, 225nm, etc.
(4) Sample injection amount: 20-35 μl; for example, 20, 25, 30. Mu.l are used.
In the invention, the derivatization reaction method comprises the steps of reacting a sample to be detected and N-ethylaniline in a solvent. The acid chloride compound is active in nature, so that the acid chloride compound can easily react with aniline substances.
Meanwhile, because the acyl chloride compound has active property, the solvent does not comprise water, alcohol and amine solvents, so that the solvent is prevented from reacting with the solvent. Acetonitrile may be used as a solvent.
The derivatization reaction time can be adjusted according to actual conditions, and the reaction endpoint is determined.
The invention also comprises the preparation of the sample solution to be detected, which comprises the following steps: by referring to the conventional method of liquid chromatography, the sample to be detected is derivatized and then dissolved in a solvent to prepare a sample solution, a reference solution, a system applicability solution, a standard sample solution and the like, wherein the solvent can be acetonitrile, methanol or the like.
Octadecyl bond and silica gel column, ostade-cylilane, abbreviated ODS. The chromatographic column can be YMC-Pack Pro C18 RS, ACE Excel 3C 18-PFP or an expected equivalent chromatographic column, and is preferably YMC-Pack Pro C18 RS.
The method can detect the content of the acryloyl chloride and related substances thereof, can directly detect the content of the acryloyl chloride and related substances thereof through liquid chromatography, and has stable and reliable detection results.
The above-mentioned derivatization method is also applicable to detection of other similar acyl chloride compounds, and the aniline substance is used as a derivatization reagent, and the aniline substance is selected from secondary amines, and is detected by using high performance liquid chromatography. The mobile phase elution condition can be properly adjusted for different acyl chloride compounds, and the acyl chloride compounds which are detected by the invention at present comprise the acryloyl chloride, the acetyl chloride, the 3-chloropropionyl chloride and the propionyl chloride.
Drawings
FIG. 1 example 1 detection chromatogram
FIG. 2 example 2 detection chromatogram
FIG. 3 comparative example detection chromatogram
Detailed Description
The following examples will help demonstrate the beneficial effects of the present invention, but they are merely illustrative of the present invention and not limiting the invention in any way.
In the present invention, SM3-YS is an N-ethylaniline derivative of acryloyl chloride, SM3-Z1-YS is an N-ethylaniline derivative of acetyl chloride, SM3-Z2-YS is an N-ethylaniline derivative of 3-chloropropionyl chloride, and SM3-Z3-YS is an N-ethylaniline derivative of propionyl chloride.
Example 1
Taking a proper amount of the product, precisely weighing, placing the product into a 50ml measuring flask, diluting the product to a scale with acetonitrile, and preparing a solution containing about 0.5mg of acryloyl chloride in each 1ml of the product as a sample stock solution.
Accurately measuring 0.2ml of N-ethylaniline, placing the solution into a 50ml measuring flask, and diluting the solution to a scale with acetonitrile to obtain N-ethylaniline stock solution.
Precisely measuring 1ml of sample stock solution and 1ml of N-ethylaniline stock solution, placing into a 10ml measuring flask, shaking uniformly, standing at normal temperature for 20min, and diluting with water to scale to obtain sample solution.
Taking a proper amount of an acryloyl chloride reference substance, precisely weighing, diluting with acetonitrile to a scale, and preparing a solution containing about 1mg of the acryloyl chloride in each 1ml of the solution as a stock solution of the acryloyl chloride reference substance.
And respectively taking a proper amount of impurity acetyl chloride, 3-chloropropionyl chloride and propionyl chloride reference substances, and preparing an impurity reference substance stock solution containing about 0.025mg of acetyl chloride, 3-chloropropionyl chloride and propionyl chloride in each 1ml by acetonitrile.
Precisely measuring 0.5ml of an acrylic chloride reference substance stock solution, 0.5ml of acetonitrile, 1.0ml of an N-ethylaniline stock solution, 100 μl of each of an acetyl chloride, 3-chloropropionyl chloride and propionyl chloride impurity reference substance stock solution, placing into a 10ml measuring flask, shaking uniformly, standing at normal temperature for 20min, diluting with water to constant volume to scale, and taking the solution as a system applicability solution.
According to the measurement of high performance liquid chromatography (rule 0512 of four edition of Chinese pharmacopoeia 2020), octadecylsilane chemically bonded silica is used as filler (YMC-Pack Pro C18 RS,4.6mm×150mm,3 μm or chromatographic column with equivalent efficacy), phosphoric acid water (pH=3.0) is used as mobile phase A, acetonitrile-methanol (1:1) is used as mobile phase B, gradient elution is carried out according to Table 1, the flow rate is 1.0ml per minute, the column temperature is 25 ℃, and the detection wavelength is 220nm.
And (3) precisely measuring 30 μl of the system applicability solution, injecting into a liquid chromatograph, recording a chromatogram, and sequentially outputting peaks of acetyl chloride derivative, acryloyl chloride derivative, propionyl chloride derivative and 3-chloropropionyl chloride derivative, wherein the separation degree of the peaks of the main component derivative and the peaks of the known impurity derivatives in the system applicability solution is not less than 1.5.
30 μl of the sample solution is precisely measured and injected into the liquid chromatograph, and the chromatogram is recorded. The sample solution has impurity peaks, each known impurity is calculated according to a peak area normalization method added with correction factors, and the unknown impurity is calculated according to a peak area normalization method (the impurity with the content less than 0.03% is ignored).
TABLE 1 gradient elution procedure
The detection pattern is shown in FIG. 1.
Table 2 results of data on linear correlations of BT-1053-SM3 and impurities thereof
Precision:
in a 6-needle system applicability solution chromatogram, the RSD of the peak area of a main peak derivative product is less than 2.0%, and the retention time RSD is less than 1.0%; the RSD of the peak area of the derivative products of all known impurities is less than 10.0%, the retention time RSD is less than 1.0%, and the result shows that the sample injection precision of the method meets the requirement.
Repeatability:
6 parts of standard-adding test samples, and calculating the content of each impurity by adopting an impurity external standard method and a correction factor peak area normalization method, wherein the obtained results all meet the RSD of less than or equal to 10.0% or the range of less than or equal to 0.03%; and the obtained results of the two different calculation methods also meet that RSD is less than or equal to 10.0 percent or the range is less than or equal to 0.03 percent. The results obtained by calculating the unknown impurities according to the peak area normalization method all meet the extremely poor of less than or equal to 0.03 percent. The results show that the reproducibility of the method is satisfactory.
Intermediate precision:
in 6 parts of the standard-adding test sample and 12 parts of the two people of the standard-adding test sample, the peak area normalization method for adding correction factors is adopted to calculate the content of each known impurity, and the obtained results all meet the RSD less than or equal to 10.0% or the range less than or equal to 0.03%; the peak area normalization method is adopted to calculate the content of each unknown impurity, and the obtained results all meet the extremely poor of less than or equal to 0.03 percent. The results show that the intermediate precision of the method meets the requirement.
Recovery rate:
under the concentration of three different levels of 50%, 100% and 150%, 3 parts of impurities are prepared in parallel at each level, the recovery rate of each impurity is in the range of 90.0% -110.0%, RSD meets the requirements under the corresponding concentration items, and the result shows that the accuracy of the method meets the requirements.
Stability:
the system applicability solution is placed for 38 hours under the room temperature condition to be stable; the test solution was stable at room temperature for 25 h.
Durability:
TABLE 3 results of the contents of various impurities dissolved in the test sample under the durability condition
Under the different conditions of the table 3, the system applicability can pass; the blank solution chromatogram has no interference peak at the peak position of the derivative products of the acryloyl chloride and the impurities; the detection of the acrylic chloride derivative is not interfered by all known impurity derivative products in a system applicability solution chromatogram, and the separation degree between peaks of the acrylic chloride derivative products and all known impurity derivative products is more than 1.5; the number of theoretical plates is larger than 5000, tailing factors are between 0.8 and 2.0, and the peak purity of the main component and the peaks of the derivative products of the known impurities meets the regulations. In the chromatogram of the solution of the standard sample, the separation degree between the peak derivative of the acrylic acid chloride and each known impurity and the adjacent impurity peaks before and after the peak derivative of the acrylic acid chloride is more than 1.2, the theoretical plate number is more than or equal to 5000, the tailing factors are all between 0.8 and 2.0, and the peak purity meets the regulations. When the derivative conditions and the chromatographic conditions are slightly changed, compared with the specified method, the detection results of the impurity acetyl chloride and propionyl chloride are extremely poor and are respectively 0.03% and 0.028%, and the detection result RSD of the impurity 3-chloropropionyl chloride is 3.8%, so that the RSD is less than 10.0% or extremely poor and is less than 0.03%; the result range of the unknown impurity calculated by the peak area normalization method is less than 0.03%, and meets the requirements. However, when the pH is 2.8, the peak sequence of the 3-chloropropionyl chloride derivative product peak and the peak sequence of the unknown impurity peak in the sample are changed, and the unknown impurity is moved to the front of the 3-chloropropionyl chloride derivative product peak, so that the durability is poor when the pH is 2.8, and the pH range is controlled within 3.0-3.2. The other results show that the method has good durability to chromatographic columns of different instruments, same brands and different batch numbers within the range of column temperature of 23-27 ℃ and the range of flow rate of 0.9-1.1 ml/min and the range of derivative time of 18-22 min.
Example 2
Mobile phase a: phosphoric acid water (ph 3.00), mobile phase B: acetonitrile: methanol (1:1), sample injection amount
The mobile phase elution gradient was 25. Mu.l as follows, with the other conditions being the same as in example 1:
the chromatogram is shown in fig. 2.
Baseline separation between SM3-Z3 derivative product and the following unknown impurity was not achieved.
Comparative example
The following chromatographic conditions were used:
mobile phase a: phosphoric acid water (ph 3.00), mobile phase B: acetonitrile; column temperature: 30 ℃, wavelength: 210nm, sample volume: 20 μl, otherwise the same as in example 1. Gradient elution was as follows:
baseline separation was not achieved, see figure 3.
Claims (5)
1. The method for detecting the acryloyl chloride and related substances is characterized in that: the related substances are acetyl chloride, 3-chloropropionyl chloride and propionyl chloride; the method uses N-ethylaniline as a derivatization reagent and uses high performance liquid chromatography for detection, and comprises the following detection conditions:
column temperature: 20-30 ℃, flow rate: 0.8-1.2 ml/min, wavelength: 220+ -5 nm
Chromatographic column: octadecyl bond and silica gel column
Mobile phase: the organic phase was acetonitrile: methanol 1:1, aqueous phase is phosphoric acid aqueous solution with pH of 3.0-3.2, and gradient elution procedure comprises:
。
2. The method of claim 1, wherein: the detection method further comprises one of the following conditions:
(1) Column temperature: 25 DEG C
(2) Flow rate: 1.0ml/min
(3) Wavelength: 220nm.
3. The method of claim 1, wherein: the method comprises the steps of derivatization reaction, wherein the reaction method comprises the steps of reacting a sample to be detected and N-ethylaniline in a solvent.
4. A detection method according to claim 3, wherein: the solvent does not include water, alcohol, amine solvents.
5. A detection method according to claim 3, wherein: the solvent is selected from acetonitrile.
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