CN113671077A - Detection method of acryloyl chloride and related substances thereof - Google Patents
Detection method of acryloyl chloride and related substances thereof Download PDFInfo
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- 238000001514 detection method Methods 0.000 title claims abstract description 36
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 239000000126 substance Substances 0.000 title claims abstract description 23
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 24
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 10
- 238000001212 derivatisation Methods 0.000 claims abstract description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 14
- 238000010828 elution Methods 0.000 claims description 12
- 239000012071 phase Substances 0.000 claims description 12
- 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 compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical group 0.000 claims description 2
- 150000003335 secondary amines Chemical group 0.000 claims description 2
- 239000012535 impurity Substances 0.000 abstract description 35
- 239000007788 liquid Substances 0.000 abstract description 5
- 238000004811 liquid chromatography Methods 0.000 abstract description 5
- 230000035945 sensitivity Effects 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 18
- 239000000523 sample Substances 0.000 description 14
- 238000010606 normalization Methods 0.000 description 7
- 239000013558 reference substance Substances 0.000 description 6
- 239000012488 sample solution Substances 0.000 description 6
- 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
- 238000007865 diluting Methods 0.000 description 4
- -1 acrylic ester Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 238000009795 derivation Methods 0.000 description 3
- 150000002894 organic compounds Chemical class 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical group CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 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 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
- 230000033228 biological regulation 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
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect 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
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 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
- 238000005070 sampling Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
Images
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
Abstract
The invention provides a detection method of acryloyl chloride and related substances thereof, which takes aniline substances as a derivative reagent and uses high performance liquid chromatography for detection. At present, no report of detecting acryloyl chloride and/or related substances thereof by adopting liquid chromatography is available, and the method adopts N-ethylaniline as a derivatization reagent, so that the method is simple and convenient to operate, short in derivatization time, high in sensitivity and less in side reaction; the ultraviolet detector is adopted to detect the known impurities and the unknown impurities in the sample in the liquid chromatogram, the application range is wide, the repeatability and the durability are good.
Description
Technical Field
The invention belongs to the field of pharmaceutical analysis, and relates to an HPLC (high performance liquid chromatography) detection method for acryloyl chloride and related substances thereof.
Background
Acryloyl chloride, a colorless flammable liquid, corrosive and irritant, and volatile. Due to the active chemical property, the organic compound can generate various chemical reactions, and derive various organic matters, such as acrylic ester and acrylamide compounds, and is an important raw material in the industries of medicine, chemical engineering and the like.
Acryloyl chloride is active in chemical property and can react with water, alcohol and amine solvents, so that the content of the acryloyl chloride is difficult to directly detect. At present, the detection method for the content of acryloyl chloride mainly comprises a gas chromatography, wherein the acryloyl chloride is firstly derived by alcohol or amine (mainly aniline) compounds, and then the detection is carried out by using the gas chromatography, but the detection by using the gas chromatography can leak and detect some unknown impurities, meanwhile, some unknown peaks in the gas chromatography can not be judged to be solvent peaks or impurity peaks, and the accurate quantification can not be carried out. At present, no report on a detection method of acryloyl chloride related substances exists.
HPLC, 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 20 th 60 s, which adopts a high-pressure infusion system to pump a mobile phase into a chromatographic column, elutes each component in the chromatographic column by adopting an isocratic or gradient elution mode, and sequentially enters a detector (ultraviolet detector (UV), Diode Array Detector (DAD), Evaporative Light Scattering Detector (ELSD) or the like) for detection, so that a sample is analyzed, and the method is widely used in the fields of medicines, foods and the like. The HPLC can be used for analyzing organic compounds with high boiling point, difficult volatilization, unstable heating, large molecular weight and different polarities, bioactive substances, high molecular compounds and the like, is suitable for analyzing 80 percent of organic compounds, makes up the defects of GC, and has the characteristics of high analysis efficiency, high selectivity, high detection sensitivity, high analysis speed and the like.
Disclosure of Invention
Based on the problems, the invention provides a method for detecting acryloyl chloride and related substances thereof by using a high performance liquid chromatography for the first time.
Specifically, the invention provides a detection method of acryloyl chloride and/or related substances thereof, aniline substances are used as a derivative reagent, and high performance liquid chromatography is used for detection, and the detection method comprises the following detection conditions:
a chromatographic column: octadecylsilane bonded silica gel column
Mobile phase: the organic phase is acetonitrile: methanol (3-1): 1, aqueous phase pH2-4, gradient elution procedure comprising:
at present, no report of detecting acryloyl chloride and/or related substances thereof by adopting liquid chromatography is available, and the method adopts N-ethylaniline as a derivatization reagent, so that the method is simple and convenient to operate, short in derivatization time, high in sensitivity and less in side reaction; the ultraviolet detector is adopted to detect the known impurities and the unknown impurities in the sample in the liquid chromatogram, the application range is wide, the repeatability and the durability are good.
The related substances in the invention are selected from acetyl chloride, 3-chloropropionyl chloride and propionyl chloride.
Wherein the aniline material is selected from aromatic secondary amines, such as N-ethyl aniline.
Wherein, in the organic phase, acetonitrile: the methanol may be selected from 3:1, 2:1, 1:1, etc.
Wherein, common organic acid and/or inorganic acid is pH regulator.
Wherein the pH regulator can be selected from conventional acidic reagents such as hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, etc. The pH can be greater than 2.8, such as 2.8-4, excluding 2.8, and can be further selected from 3.0-3.2.
Further, the gradient elution procedure for the first 26min was:
alternatively, the gradient elution procedure for the first 28min was:
the detection method of the invention also 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. are used.
(4) Sample introduction amount: 20-35 μ l; for example, 20, 25, 30. mu.l are used.
In the invention, the derivatization reaction method comprises the step of reacting a sample to be detected and N-ethylaniline in a solvent. Due to the active nature of the acid chloride compound, the compound is easy to react with aniline substances.
Meanwhile, because the acyl chloride compound is active, the solvent does not comprise water, alcohol and amine solvents, so that the solvent and the solvent are prevented from reacting. 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: referring to the conventional method of liquid chromatography, a sample to be detected is derivatized and dissolved in a solvent to prepare a test solution, a reference solution, a system applicability solution, a labeled test solution and the like, wherein the solvent can be acetonitrile, methanol or the like.
Octadecyl bond and silica gel column, ostade-cyclane, abbreviated as ODS. The chromatographic column of the invention can be selected from YMC-Pack Pro C18 RS, ACE Excel 3C 18-PFP or expected equivalent chromatographic column, preferably YMC-Pack Pro C18 RS.
The method of the invention not only can detect the acryloyl chloride and related substances thereof, but also can directly measure the content of the acryloyl chloride and related substances thereof by liquid chromatography, and the detection result is stable and reliable.
The derivation method is also suitable for detecting other similar acyl chloride compounds, aniline substances are used as a derivation reagent, the aniline substances are selected from secondary amine, and high performance liquid chromatography is used for detecting. For different acyl chloride compounds, the elution conditions of the mobile phase can be properly adjusted, and the acyl chloride compounds detected at present comprise acryloyl chloride, acetyl chloride, 3-chloropropionyl chloride and propionyl chloride.
Drawings
FIG. 1 example 1 detection chromatogram
FIG. 2 example 2 detection chromatogram
FIG. 3 example 2 comparative example detection chromatogram
Detailed Description
The following examples will help demonstrate the beneficial effects of the present invention, but they are only for illustrative purposes and do not limit the present invention in any way.
In the 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 in a 50ml measuring flask, diluting to scale with acetonitrile, and preparing into a solution containing about 0.5mg of acryloyl chloride in each 1ml as a test sample storage solution.
0.2ml of N-ethylaniline is precisely measured, placed in a 50ml measuring flask, diluted to the scale with acetonitrile and used as a N-ethylaniline stock solution.
Precisely measuring 1ml of the sample solution and 1ml of the N-ethylaniline solution, placing the sample solution and the N-ethylaniline solution in a 10ml measuring flask, shaking up, standing at normal temperature for 20min, and diluting with water to a scale to obtain the sample solution.
Taking a proper amount of acryloyl chloride reference substance, precisely weighing, diluting to scale with acetonitrile, and preparing a solution containing about 1mg of acryloyl chloride in each 1ml as an acryloyl chloride reference substance storage solution.
Taking appropriate amount of reference substances of acetyl chloride, 3-chloropropionyl chloride and propionyl chloride as impurities, and preparing impurity reference substance stock solution containing acetyl chloride, 3-chloropropionyl chloride and propionyl chloride respectively in an amount of about 0.025mg in each 1ml with acetonitrile.
Accurately measuring 0.5ml of acryloyl chloride reference substance storage solution, 0.5ml of acetonitrile, 1.0ml of N-ethylaniline storage solution, 100 mu l of each of acetyl chloride, 3-chloropropionyl chloride and propionyl chloride impurity reference substance storage solution, putting the solutions into a 10ml measuring flask, shaking up, standing at normal temperature for 20min, diluting with water to a constant volume to obtain a system applicability solution.
The elution was performed by high performance liquid chromatography (0512, the four ministry of China pharmacopoeia 2020 edition), using octadecylsilane chemically bonded silica as a filler (YMC-Pack Pro C18 RS, 4.6 mm. times.150 mm, 3 μm or a column with equivalent performance), using phosphoric acid water (pH 3.0) as a mobile phase A and acetonitrile-methanol (1:1) as a mobile phase B, and performing gradient elution according to Table 1 at a flow rate of 1.0ml per minute, a column temperature of 25 ℃ and a detection wavelength of 220 nm.
Precisely measuring 30 mu l of system applicability solution, injecting into a liquid chromatograph, recording a chromatogram, and sequentially outputting peaks of acetyl chloride derivatives, acryloyl chloride derivatives, propionyl chloride derivatives and 3-chloropropionyl chloride derivatives, wherein the separation degree of each peak of main component derivatives and known impurity derivatives in the system applicability solution is not less than 1.5.
Precisely measuring 30 μ l of the sample solution, injecting into a liquid chromatograph, and recording chromatogram. If the sample solution has impurity peaks, each known impurity is calculated according to a peak area normalization method added with a correction factor, and the unknown impurity is calculated according to the peak area normalization method (the impurity with the content less than 0.03 percent is ignored).
TABLE 1 gradient elution procedure
The detection profile is shown in FIG. 1.
TABLE 2 BT-1053-SM3 Linear correlation data results for its impurities
Precision:
in a 6-pin system applicability solution chromatogram, the RSD of the peak area of a main peak derived product is less than 2.0 percent, and the retention time RSD is less than 1.0 percent; RSD of the peak area of each known impurity derived product is less than 10.0%, and RSD of retention time is less than 1.0%, and results show that the sampling precision of the method meets requirements.
Repeatability:
6 parts of standard sample is added, the content of each impurity is calculated by adopting an impurity external standard method and a correction factor added peak area normalization method, and the obtained results meet the condition that RSD is less than or equal to 10.0 percent or range difference is less than or equal to 0.03 percent; and the results obtained by the two different calculation methods also meet the condition that the RSD is less than or equal to 10.0 percent or the range difference is less than or equal to 0.03 percent. The results of the unknown impurities calculated according to the peak area normalization method all meet the range difference of less than or equal to 0.03 percent. The results show that the reproducibility of the method meets the requirements.
Intermediate precision:
in 6 parts of standard sample and 12 parts of standard sample, calculating the content of each known impurity by adopting a peak area normalization method with a correction factor, wherein the RSD is less than or equal to 10.0 percent or the range difference is less than or equal to 0.03 percent; the results obtained by calculating the content of each unknown impurity by adopting a peak area normalization method meet the range difference of less than or equal to 0.03 percent. The results show that the intermediate precision of the method meets the requirements.
And (3) recovery rate:
under the concentration of three different levels of 50%, 100% and 150%, 3 parts are prepared in parallel in each level, the recovery rate of each impurity is in the range of 90.0% -110.0%, RSD meets the requirement under the corresponding concentration item, and the result shows that the accuracy of the method meets the requirement.
Stability:
the system applicability solution is stable after being placed for 38h at room temperature; the test solution is stable after being placed for 25h at room temperature.
Durability:
TABLE 3 result table of the content of each impurity dissolved in the test article under the durability condition
Under the different conditions of the above table 3, the system applicability can be passed; the blank solution chromatogram has no interference peak at the peak position of acryloyl chloride and each impurity derived product; the detection of the acryloyl chloride derivative product is not interfered by each known impurity derivative product in a system applicability solution chromatogram, and the separation degree between the acryloyl chloride derivative product and each known impurity derivative product peak is more than 1.5; and (3) counting by using the chromatographic peak of the acryloyl chloride derivative product, wherein the number of theoretical plates is more than 5000, tailing factors are between 0.8 and 2.0, and the peak purity of the main component and each known impurity derivative product peak meets the specification. In the chromatogram of the solution of the standard sample, the separation degrees between the acryloyl chloride derivative product and each known impurity peak derivative and the adjacent impurity peaks before and after the acryloyl chloride derivative product are both greater than 1.2, the number of theoretical plates is greater than or equal to 5000 by the chromatographic peak of the acryloyl chloride derivative product, the tailing factors are both between 0.8 and 2.0, and the peak purities meet the regulations. When the derivation condition and the chromatographic condition are slightly changed, compared with a specified method, the detection results of the impurities acetyl chloride and propionyl chloride are respectively 0.03 percent and 0.028 percent, and the detection result RSD of the impurity 3-chloropropionyl chloride is 3.8 percent, which meet the condition that the RSD is less than 10.0 percent or the range is less than 0.03 percent; the range of results of the unknown impurities calculated by a peak area normalization method is less than 0.03 percent, and the requirements are met. However, when the pH is 2.8, the peak appearance sequence of the 3-chloropropionyl chloride derived product in the sample and the peak appearance sequence of the unknown impurity in the sample changes, and the unknown impurity moves to the front of the peak of the 3-chloropropionyl chloride derived product, so the durability is poor when the pH is 2.8, and therefore, the pH range is controlled to be 3.0-3.2. The other results show that the method has good durability to chromatographic columns of different instruments, same brand and same type and different batch numbers within the range of column temperature of 23-27 ℃, flow rate of 0.9-1.1 ml/min and derivatization time of 18-22 min.
Example 2
Mobile phase A: phosphoric acid water (ph3.00), mobile phase B: acetonitrile: methanol (1:1), sample size
25 μ l, mobile phase elution gradient as follows, other conditions were the same as in example 1:
the chromatogram is shown in FIG. 2.
Baseline separation was not achieved between the SM 3-Z3-derived product and subsequently unknown impurities.
Comparative example
The following chromatographic conditions were used:
mobile phase A: phosphoric acid water (ph3.00), mobile phase B: acetonitrile; column temperature: 30 ℃, wavelength: 210nm, sample injection volume: 20 μ l, other conditions were the same as in example 1. The gradient elution was as follows:
baseline separation was not achieved, see figure 3.
Claims (9)
1. The detection method of acryloyl chloride and/or related substances thereof is characterized in that: the method comprises the following steps of (1) detecting by using high performance liquid chromatography with aniline substances as a derivatization reagent, wherein the detection conditions comprise:
a chromatographic column: octadecyl bond and silica gel column
Mobile phase: the organic phase is acetonitrile: methanol (3-1): 1, aqueous phase pH2-4, gradient elution procedure comprising:
2. the detection method according to claim 1, characterized in that: the related substances comprise acetyl chloride, 3-chloropropionyl chloride and propionyl chloride.
3. The detection method according to claim 1, characterized in that: the aniline is selected from secondary amines.
4. The detection method according to claim 1, characterized in that: in the organic phase, acetonitrile: the methanol is 1: 1.
5. the detection method according to claim 1, characterized in that: the pH regulator used in the water phase is selected from organic acid and/or inorganic acid, and further selected from hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, and acetic acid.
6. The detection method according to claim 1, characterized in that: the gradient elution procedure included:
or
7. The detection method according to claim 1, characterized in that: the detection method further comprises one of the following conditions:
(1) column temperature: 20-30 ℃; further selected from 25 deg.C
(2) Flow rate: 0.8-1.2 ml/min; further selected from 1.0ml/min
(3) Wavelength: 220 +/-5 nm; further selected from 220 nm.
8. The detection method according to claim 1, characterized in that: the method comprises the steps of carrying out derivatization reaction, wherein the reaction method comprises the step of reacting a sample to be detected and N-ethylaniline in a solvent.
9. The detection method according to claim 8, characterized in that: the solvent does not comprise water, alcohol and amine solvents; further, the solvent is selected from acetonitrile.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114689751A (en) * | 2022-03-30 | 2022-07-01 | 山东省食品药品检验研究院 | Non-target screening method for alkylating genotoxic impurities |
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