CN114264752A - Detection method of methyl bromoacetate - Google Patents

Detection method of methyl bromoacetate Download PDF

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CN114264752A
CN114264752A CN202111635578.0A CN202111635578A CN114264752A CN 114264752 A CN114264752 A CN 114264752A CN 202111635578 A CN202111635578 A CN 202111635578A CN 114264752 A CN114264752 A CN 114264752A
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methyl bromoacetate
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CN114264752B (en
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孟庆博
李莉
安勇
邵旭
黄海玉
王立茹
向宏艳
段月晓
崔娅丽
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Beijing Jincheng Taier Pharmaceutical Co ltd
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Abstract

The invention belongs to the technical field of medicine detection, and particularly relates to a method for detecting methyl bromoacetate. The content of methanol, methoxy acetic acid, bromo acetic acid and methoxy methyl acetate in methyl bromoacetate is determined by gas chromatography. The method can effectively separate the methanol, the methyl methoxyacetate, the methoxyacetic acid, the methyl bromoacetate and the bromoacetic acid, and can quickly, efficiently and accurately determine the contents of the methanol, the methoxyacetic acid, the bromoacetic acid and the methyl methoxyacetate in the methyl bromoacetate.

Description

Detection method of methyl bromoacetate
Technical Field
The invention belongs to the technical field of medicine detection, and particularly relates to a method for detecting methyl bromoacetate.
Background
Methyl bromoacetate is a chemical raw material, can be used for synthesizing herbicides and can also be used as an intermediate for synthesizing dyes and medicaments. In the prior art, when the content of methyl bromoacetate is measured by adopting a gas chromatography, the temperature of a chromatographic column is usually constant, and the content of the methyl bromoacetate is calculated by adopting an area normalization method through a peak area, but other impurity components possibly contained in the methyl bromoacetate cannot be effectively separated.
Chinese patent CN 113049712A discloses a method for measuring the content of cyclopropyl methyl ketone, which comprises the following steps: (i) providing a sample solution to be detected and an internal standard solution; (ii) injecting sample solution to be detected and internal standard solution and carrying out gas chromatography analysis to obtain corresponding gas chromatogram so as to obtain the content of cyclopropyl methyl ketone in the sample to be detected; wherein the gas chromatography is carried out using a medium polarity capillary chromatography column. The patent aims at the content determination of the pharmaceutical intermediate cyclopropyl methyl ketone, has strong specificity and cannot be used for reference in the detection of other medicines.
At present, a need exists for providing a rapid, efficient and accurate method for detecting methyl bromoacetate.
Disclosure of Invention
The invention aims to provide a method for detecting methyl bromoacetate, which can effectively separate methanol, methyl methoxyacetate, methoxyacetic acid, methyl bromoacetate and bromoacetic acid and can quickly, efficiently and accurately determine the contents of the methanol, the methoxyacetic acid, the bromoacetic acid and the methyl methoxyacetate in the methyl bromoacetate.
The detection method of methyl bromoacetate adopts gas chromatography to measure the content of methanol, methoxy acetic acid, bromoacetic acid and methyl methoxy acetate in the methyl bromoacetate.
The detection method of methyl bromoacetate specifically comprises the steps of preparing a reference solution and a test solution, sequentially injecting a blank solvent, the test solution and the reference solution into a gas chromatograph, recording a gas chromatogram, and determining the content of methanol, methoxyacetic acid, bromoacetic acid and methyl methoxyacetate in the test solution by adopting an external standard method.
The preparation method of the reference solution comprises the steps of measuring 1ml of methanol stock solution, 1ml of methoxy methyl acetate stock solution, 1ml of methoxy acetic acid stock solution, 1ml of bromoacetic acid stock solution and 1ml of bromomethyl acetate stock solution, diluting the solution to 10ml by using a diluent, and shaking up the solution to obtain the reference solution.
The preparation method of the methanol stock solution comprises the steps of taking 50mg of methanol, diluting the methanol to 10ml by using a diluent, and shaking up the methanol to obtain the methanol stock solution;
the preparation method of the methyl methoxyacetate stock solution comprises the steps of taking 50mg of methyl methoxyacetate, diluting the methyl methoxyacetate to 10ml by using a diluent, and shaking up the methyl methoxyacetate stock solution to obtain the methyl methoxyacetate stock solution;
the preparation method of the methoxy acetic acid stock solution comprises taking 50mg of methoxy acetic acid, diluting to 10ml with diluent, and shaking up to obtain the methoxy acetic acid stock solution;
the preparation method of bromoacetic acid stock solution comprises taking 50mg of bromoacetic acid, diluting with diluent to 10ml, and shaking up to obtain;
the preparation method of the methyl bromoacetate stock solution comprises the steps of taking 50mg of methyl bromoacetate, diluting the methyl bromoacetate to 10ml by using a diluent, and shaking up the methyl bromoacetate stock solution to obtain the methyl bromoacetate stock solution.
The preparation method of the test solution comprises the steps of taking 1g of methyl bromoacetate sample, adding a diluent to dilute the sample to 10ml, and shaking up the sample to obtain the test solution.
The diluent is acetonitrile.
The blank solvent is acetonitrile.
The chromatographic conditions in the gas chromatography are as follows:
a chromatographic column: a quartz capillary column with stationary phase 5% phenyl 95% dimethyl polysiloxane;
sample inlet temperature: 135 ℃ and 145 ℃;
a detector: flame ionization detector FID;
detector temperature: 195 ℃ and 205 ℃;
the split ratio is as follows: 3-7: 1;
carrier gas: nitrogen gas;
carrier gas flow: 3.8-4.2 ml/min;
and (3) sample introduction mode: directly feeding a sample;
sample introduction amount: 1 mul;
column box temperature program: the initial column box temperature is kept at 40-50 ℃ for 1min, the temperature is raised to 130 ℃ at 10 ℃/min for 10min, and the temperature is raised to 200 ℃ at 20 ℃/min for 4 min.
The detection method of methyl bromoacetate further comprises the steps of preparing a sample adding solution, injecting the sample adding solution into a gas chromatograph, recording a gas chromatogram, and comparing and verifying the chromatogram of the sample adding solution, the chromatogram of the sample solution and the chromatogram of a reference solution.
The preparation method of the sample labeling solution comprises the steps of taking 1g of methyl bromoacetate sample, adding 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of methoxyacetic acid stock solution and 1ml of bromoacetic acid stock solution, diluting to 10ml with a diluent, and shaking up to obtain the reagent labeling solution.
The purpose of the sample added with the standard solution is to investigate and verify whether the separation degree between the known impurities (methanol, methyl methoxyacetate, methoxyacetic acid and bromoacetic acid) and the adjacent peak and the separation degree between the methyl bromoacetate and the adjacent peak meet the requirement that the separation degree is more than 1.5.
The invention has the following beneficial effects:
in the prior art, the temperature of a chromatographic column is usually constant when gas chromatography is adopted for detection, the content of methyl bromoacetate is calculated by adopting an area normalization method according to the peak area, and the impurity components in the methyl bromoacetate are measured by the chromatographic column at constant temperature, so that the separation is difficult, and the quality of the methyl bromoacetate cannot be strictly controlled. According to the invention, based on a synthetic route of methyl bromoacetate, the impurity spectra are prepared into methanol, methyl methoxyacetate, methoxyacetic acid and bromoacetic acid, and the possibility of causing side reaction is reduced by controlling the limit level of impurities, so that the quality of methyl bromoacetate is controlled.
The method can effectively separate the methanol, the methyl methoxyacetate, the methoxyacetic acid, the methyl bromoacetate and the bromoacetic acid, and can quickly, efficiently and accurately determine the contents of the methanol, the methoxyacetic acid, the bromoacetic acid and the methyl methoxyacetate in the methyl bromoacetate.
Drawings
FIG. 1 is a chromatogram of an air-white solvent in example 1.
FIG. 2 is a chromatogram of the test solution in example 1.
FIG. 3 is a chromatogram of the sample addition solution in example 1.
FIG. 4 is a chromatogram of the control solution of example 1.
FIG. 5 is a chromatogram of an air-white solvent in example 2.
FIG. 6 is a chromatogram of the test solution in example 2.
FIG. 7 is a chromatogram of the sample-spiking solution in example 2.
FIG. 8 is a chromatogram of the control solution of example 2.
FIG. 9 is a chromatogram of an air-white solvent in example 3.
FIG. 10 is a chromatogram of the test solution in example 3.
FIG. 11 is a chromatogram of the control solution of example 3.
Detailed Description
The present invention is further described below with reference to examples.
Example 1
(1) The preparation method of the reference solution comprises weighing methanol stock solution 1ml, methyl methoxyacetate stock solution 1ml, methoxyacetic acid stock solution 1ml, bromoacetic acid stock solution 1ml and methyl bromoacetate stock solution 1ml, diluting with acetonitrile to 10ml, and shaking.
The preparation method of the methanol stock solution comprises taking 50mg of methanol, diluting with acetonitrile to 10ml, and shaking up to obtain the final product;
the preparation method of the methyl methoxyacetate stock solution comprises the steps of taking 50mg of methyl methoxyacetate, diluting the methyl methoxyacetate to 10ml with acetonitrile, and shaking up the methyl methoxyacetate stock solution to obtain the methyl methoxyacetate stock solution;
the preparation method of the methoxy acetic acid stock solution comprises the steps of taking 50mg of methoxy acetic acid, diluting the methoxy acetic acid to 10ml with acetonitrile, and shaking up the methoxy acetic acid stock solution to obtain the methoxy acetic acid stock solution;
the preparation method of bromoacetic acid stock solution comprises taking 50mg of bromoacetic acid, diluting to 10ml with acetonitrile, and shaking up to obtain;
the preparation method of the methyl bromoacetate stock solution comprises the steps of taking 50mg of methyl bromoacetate, diluting the methyl bromoacetate to 10ml with acetonitrile, and shaking up the methyl bromoacetate stock solution to obtain the methyl bromoacetate stock solution.
(2) The test solution is prepared by taking 1g of methyl bromoacetate sample, adding acetonitrile to dilute to 10ml, and shaking up.
(3) The blank solvent was acetonitrile.
(4) The preparation method of the sample added standard solution comprises taking 1g of methyl bromoacetate sample, adding 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of methoxyacetic acid stock solution and 1ml of bromoacetic acid stock solution, diluting to 10ml with acetonitrile, and shaking up to obtain the final product.
(5) The specificity is as follows: preparing the blank solvent, the test solution, the reference solution and the test and standard solution.
(6) And (4) quantitative limit: measuring 1ml of the reference solution, putting the reference solution into a 10ml measuring flask, adding 0.1ml of bromoacetic acid stock solution, diluting the reference solution to 10ml with acetonitrile, and shaking up to obtain the quantitative limiting solution.
(7) Detection limit: measuring 0.02ml of methanol stock solution, 0.1ml of methoxy methyl acetate stock solution, 0.25ml of methoxy acetic acid stock solution, 1ml of bromoacetic acid stock solution and 0.25ml of bromomethyl acetate stock solution, diluting to 500ml with acetonitrile, and shaking up to obtain the detection limit solution.
(8) Linear solution: respectively measuring appropriate amounts of methanol stock solution, methoxy methyl acetate stock solution, methoxy acetic acid stock solution, bromoacetic acid stock solution and bromomethyl acetate stock solution, and diluting with acetonitrile to obtain a series of solutions with concentrations:
a solution containing 0.1mg of methanol, 0.1mg of methyl methoxyacetate, 0.1mg of methoxyacetic acid, 0.1mg of bromoacetic acid and 0.1mg of methyl bromoacetate per 1 ml;
a solution containing 0.3mg of methanol, 0.3mg of methyl methoxyacetate, 0.3mg of methoxyacetic acid, 0.3mg of bromoacetic acid and 0.3mg of methyl bromoacetate per 1 ml;
a solution containing 0.4mg of methanol, 0.4mg of methyl methoxyacetate, 0.4mg of methoxyacetic acid, 0.4mg of bromoacetic acid and 0.4mg of methyl bromoacetate per 1 ml;
a solution containing 0.5mg of methanol, 0.5mg of methyl methoxyacetate, 0.5mg of methoxyacetic acid, 0.5mg of bromoacetic acid and 0.5mg of methyl bromoacetate per 1 ml;
a solution containing 0.8mg of methanol, 0.8mg of methyl methoxyacetate, 0.8mg of methoxyacetic acid, 0.8mg of bromoacetic acid and 0.8mg of methyl bromoacetate per 1 ml;
each 1ml solution contained 1mg of methanol, 1mg of methyl methoxyacetate, 1mg of methoxyacetic acid, 1mg of bromoacetic acid and 1mg of methyl bromoacetate.
(9) Precision: taking 1g of methyl bromoacetate sample, placing the sample in a 10ml measuring flask, sequentially adding 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of methoxyacetic acid stock solution and 1ml of bromoacetic acid stock solution, diluting the mixture to 10ml with acetonitrile, and shaking up to obtain the precision solution (12 parts in parallel).
(10) And (3) recovery rate:
and (3) quantitative limiting concentration: taking 1g of methyl bromoacetate sample, placing the sample in a 10ml measuring flask, sequentially adding 1ml of reference substance solution and 0.1ml of bromoacetic acid stock solution, diluting the sample to 10ml with acetonitrile, and shaking up to obtain the product (3 parts are prepared in parallel).
50% limiting concentration: taking 1g of methyl bromoacetate sample, placing the sample in a 10ml measuring flask, sequentially adding 0.5ml of methanol stock solution, 0.5ml of methoxy methyl acetate stock solution, 0.5ml of methoxy acetic acid stock solution and 0.5ml of bromoacetic acid stock solution, diluting the mixture to 10ml with acetonitrile, and shaking up to obtain the product (3 parts are prepared in parallel).
100% limit concentration: taking 1g of methyl bromoacetate sample, placing the sample in a 10ml measuring flask, sequentially adding 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of methoxyacetic acid stock solution and 1ml of bromoacetic acid stock solution, diluting the mixture to 10ml with acetonitrile, and shaking up to obtain the product (3 parts in parallel).
150% limit concentration: taking 1g of methyl bromoacetate sample, placing the sample in a 10ml measuring flask, sequentially adding 1.5ml of methanol stock solution, 1.5ml of methoxy methyl acetate stock solution, 1.5ml of methoxy acetic acid stock solution and 1.5ml of bromoacetic acid stock solution, diluting the mixture to 10ml with acetonitrile, and shaking up to obtain the product (3 parts are prepared in parallel).
(11) Sample detection: samples of methyl bromoacetate of batch 1, batch 2 and batch 3 are taken respectively to prepare methyl bromoacetate test solution of different batches.
(12) The determination method comprises the following steps: precisely measuring blank solvent, sample solution, reference solution, sample adding solution, limit solution, detection limit solution, linear solution, precision solution and recovery solution, respectively 1 μ l, and injecting into gas chromatograph under the conditions shown in Table 1, recording chromatogram, and showing the results of specific chromatogram in FIGS. 1, 2, 3 and 4. Specificity, quantitation limit, detection limit, linearity, precision, recovery rate and sample detection results are shown in tables 2-8.
Table 1 chromatographic conditions for example 1
Figure BDA0003441999960000051
TABLE 2 results of specificity test
Figure BDA0003441999960000052
Figure BDA0003441999960000061
TABLE 3 detection of quantitative limits
Peak name Limit concentration mg/ml for quantification Is equivalent to the sample solution% Signal to noise ratio
Methanol 0.0492 0.05 352.4
Methoxyacetic acid methyl ester 0.0499 0.05 240.6
Methoxy acetic acid 0.0591 0.06 143.2
Bromoacetic acid methyl ester 0.0539 0.05 129.2
Bromoacetic acid 0.1007 0.10 93.5
TABLE 4 detection Limit test results
Peak name Detection limit concentration mg/ml Is equivalent to the sample solution% Signal to noise ratio
Methanol 0.0002 0.0002 6.9
Methoxyacetic acid methyl ester 0.0010 0.0010 4.4
Methoxy acetic acid 0.0030 0.0030 3.7
Bromoacetic acid methyl ester 0.0027 0.0027 6.0
Bromoacetic acid 0.0101 0.0101 5.3
TABLE 5 Linear test results
Peak assignment Linear equation of equations Slope of Intercept of a beam 25% of the 100% response value Coefficient of correlation r
Methanol y＝22.7592x+0.4017 22.7592 0.4017 2.8496 0.9979
Methoxyacetic acid methyl ester y＝18.0340x+0.2405 18.0340 0.2405 2.2423 0.9988
Methoxy acetic acid y＝11.8219x+0.0291 11.8219 0.0291 1.6949 0.9990
Bromoacetic acid methyl ester y＝11.3200x+0.1879 11.3200 0.1879 1.5498 0.9989
Bromoacetic acid y＝7.1572x-0.0052 7.1572 0.0052 0.8738 0.9987
TABLE 6 results of precision measurement
Serial number Methanol Methoxyacetic acid methyl ester Methoxy acetic acid Bromoacetic acid
1 0.532 0.693 0.629 0.597
2 0.528 0.691 0.627 0.597
3 0.523 0.687 0.624 0.592
4 0.534 0.696 0.634 0.603
5 0.524 0.690 0.627 0.596
6 0.525 0.690 0.625 0.595
7 0.567 0.668 0.594 0.587
8 0.567 0.668 0.596 0.590
9 0.565 0.663 0.593 0.588
10 0.563 0.663 0.593 0.588
11 0.567 0.668 0.598 0.592
12 0.532 0.668 0.598 0.592
12 parts by weight average content% 0.544 0.679 0.612 0.593
RSD％ 3.61 1.95 2.80 0.79
TABLE 7 results of recovery test
Figure BDA0003441999960000071
Figure BDA0003441999960000081
TABLE 8 results of sample examination
Test solution Batch 1 Batch 2 Batch 3
Methanol content 0.006％ 0.060％ 0.190％
Methyl methoxyacetate content 0.126％ 0.150％ 0.130％
Content of methoxyacetic acid Not detected out Not detected out Not detected out
Content of Bromoacetic acid Not detected out 0.050％ 0.250％
And (4) conclusion: under the chromatographic conditions of the example 1, the blank solvent does not interfere the measurement, and the separation degrees of each known impurity and adjacent peak, and main component peak and adjacent peak in the sample adding solution are both more than 1.5, so that the separation is good. Proved by methodology, the quantitative limit, the detection limit, the linearity, the precision and the recovery rate are all good.
Known impurities of methanol 0.006% and methyl methoxyacetate 0.126% were detected in the test solution of batch 1, and bromoacetic acid and methoxyacetic acid were not detected. Known impurities of methanol 0.060%, methyl methoxyacetate 0.150% and bromoacetic acid 0.050% were detected in the test solution of batch 2, and methoxyacetic acid was not detected. Known impurities of methanol 0.190%, methyl methoxyacetate 0.130% and bromoacetic acid 0.250% were detected in the test solution of batch 3, and methoxyacetic acid was not detected.
In conclusion, the chromatographic conditions of the embodiment 1 are adopted to detect methanol, methyl methoxyacetate, methoxyacetic acid and bromoacetic acid in methyl bromoacetate, and the impurity detection capability is good.
Example 2
(1) The preparation method of the reference solution comprises weighing methanol stock solution 1ml, methyl methoxyacetate stock solution 1ml, methoxyacetic acid stock solution 1ml, bromoacetic acid stock solution 1ml and methyl bromoacetate stock solution 1ml, diluting with acetonitrile to 10ml, and shaking.
The preparation method of the methanol stock solution comprises taking 50mg of methanol, diluting with acetonitrile to 10ml, and shaking up to obtain the final product;
the preparation method of the methyl methoxyacetate stock solution comprises the steps of taking 50mg of methyl methoxyacetate, diluting the methyl methoxyacetate to 10ml with acetonitrile, and shaking up the methyl methoxyacetate stock solution to obtain the methyl methoxyacetate stock solution;
the preparation method of the methoxy acetic acid stock solution comprises the steps of taking 50mg of methoxy acetic acid, diluting the methoxy acetic acid to 10ml with acetonitrile, and shaking up the methoxy acetic acid stock solution to obtain the methoxy acetic acid stock solution;
the preparation method of bromoacetic acid stock solution comprises taking 50mg of bromoacetic acid, diluting to 10ml with acetonitrile, and shaking up to obtain;
the preparation method of the methyl bromoacetate stock solution comprises the steps of taking 50mg of methyl bromoacetate, diluting the methyl bromoacetate to 10ml with acetonitrile, and shaking up the methyl bromoacetate stock solution to obtain the methyl bromoacetate stock solution.
(2) The test solution is prepared by taking 1g of methyl bromoacetate sample, adding acetonitrile to dilute to 10ml, and shaking up.
(3) The blank solvent was acetonitrile.
(4) The preparation method of the sample added standard solution comprises taking 1g of methyl bromoacetate sample, adding 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of methoxyacetic acid stock solution and 1ml of bromoacetic acid stock solution, diluting to 10ml with acetonitrile, and shaking up to obtain the final product.
(5) The determination method comprises the following steps: precisely measuring 1 μ l of each of the blank solvent, the test solution, the reference solution and the test solution and adding the standard solution into a gas chromatograph, wherein the chromatographic conditions are shown in Table 9, the chromatogram is recorded, the chromatographic results are shown in FIG. 5, FIG. 6, FIG. 7 and FIG. 8, the contents of methanol, methoxy acetic acid, bromoacetic acid and methyl methoxy acetate in the test solution are obtained by measuring the peak area by adopting an external standard method, and the detection results of the test solution, the reference solution and the test solution and adding the standard solution are shown in Table 10.
Table 9 chromatographic conditions for example 2
Figure BDA0003441999960000091
TABLE 10 test results of the test article solution, the test article spiking solution and the control article solution of example 2
Figure BDA0003441999960000092
Figure BDA0003441999960000101
And (4) conclusion: under the chromatographic conditions of the example 2, the separation degrees of each known impurity and adjacent peak, and main component peak and adjacent peak in the sample adding solution are both more than 1.5, and the separation is good. The known impurities of methanol 0.007% and methyl methoxyacetate 0.133% are detected in the test solution, and bromoacetic acid and methoxyacetic acid are not detected.
Example 3
(1) The preparation method of the reference solution comprises weighing methanol stock solution 1ml, methyl methoxyacetate stock solution 1ml, methoxyacetic acid stock solution 1ml, bromoacetic acid stock solution 1ml and methyl bromoacetate stock solution 1ml, diluting with acetonitrile to 10ml, and shaking.
The preparation method of the methanol stock solution comprises taking 50mg of methanol, diluting with acetonitrile to 10ml, and shaking up to obtain the final product;
the preparation method of the methyl methoxyacetate stock solution comprises the steps of taking 50mg of methyl methoxyacetate, diluting the methyl methoxyacetate to 10ml with acetonitrile, and shaking up the methyl methoxyacetate stock solution to obtain the methyl methoxyacetate stock solution;
the preparation method of the methoxy acetic acid stock solution comprises the steps of taking 50mg of methoxy acetic acid, diluting the methoxy acetic acid to 10ml with acetonitrile, and shaking up the methoxy acetic acid stock solution to obtain the methoxy acetic acid stock solution;
the preparation method of bromoacetic acid stock solution comprises taking 50mg of bromoacetic acid, diluting to 10ml with acetonitrile, and shaking up to obtain;
the preparation method of the methyl bromoacetate stock solution comprises the steps of taking 50mg of methyl bromoacetate, diluting the methyl bromoacetate to 10ml with acetonitrile, and shaking up the methyl bromoacetate stock solution to obtain the methyl bromoacetate stock solution.
(2) The test solution is prepared by taking 1g of methyl bromoacetate sample, adding acetonitrile to dilute to 10ml, and shaking up.
(3) The blank solvent was acetonitrile.
(4) The determination method comprises the following steps: precisely measuring 1 μ l of each of the blank solvent, the test solution and the reference solution, injecting into a gas chromatograph, recording chromatogram under the chromatographic conditions shown in Table 11, recording the chromatogram, and obtaining the contents of methanol, methoxy acetic acid, bromoacetic acid and methyl methoxy acetate in the test solution by peak area measurement with an external standard method, wherein the detection results of the test solution and the reference solution are shown in Table 12.
Table 11 chromatographic conditions for example 3
Figure BDA0003441999960000111
TABLE 12 test results of the test solution and the control solution of example 3
Figure BDA0003441999960000112
And (4) conclusion: under the chromatographic conditions of the example 3, the separation degree of each known impurity and adjacent peak and the separation degree of each known impurity and adjacent peak in the reference solution are both more than 1.5, and the separation is good. The known impurities of methanol 0.007% and methyl methoxyacetate 0.125% are detected in the test solution, and bromoacetic acid and methoxyacetic acid are not detected.

Claims (10)

1. A method for detecting methyl bromoacetate is characterized in that the content of methanol, methoxy acetic acid, bromoacetic acid and methyl methoxy acetate in the methyl bromoacetate is determined by adopting a gas chromatography.
2. The method for detecting methyl bromoacetate according to claim 1, wherein a reference solution and a sample solution are prepared, the blank solvent, the sample solution and the reference solution are sequentially injected into a gas chromatograph, a gas chromatogram is recorded, and the content of methanol, methoxyacetic acid, bromoacetic acid and methyl methoxyacetate in the sample solution is determined by an external standard method.
3. The method for detecting methyl bromoacetate according to claim 2, wherein the reference solution is prepared by measuring 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of bromoacetate stock solution and 1ml of methyl bromoacetate stock solution, diluting the solution with a diluent to 10ml, and shaking the diluted solution.
4. The method for detecting methyl bromoacetate according to claim 3, wherein the preparation method of the methanol stock solution is to take 50mg of methanol, dilute the methanol to 10ml by using a diluent, and shake the methanol stock solution uniformly to obtain the methyl bromoacetate;
the preparation method of the methyl methoxyacetate stock solution comprises the steps of taking 50mg of methyl methoxyacetate, diluting the methyl methoxyacetate to 10ml by using a diluent, and shaking up the methyl methoxyacetate stock solution to obtain the methyl methoxyacetate stock solution;
the preparation method of the methoxy acetic acid stock solution comprises taking 50mg of methoxy acetic acid, diluting to 10ml with diluent, and shaking up to obtain the methoxy acetic acid stock solution;
the preparation method of bromoacetic acid stock solution comprises taking 50mg of bromoacetic acid, diluting with diluent to 10ml, and shaking up to obtain;
the preparation method of the methyl bromoacetate stock solution comprises the steps of taking 50mg of methyl bromoacetate, diluting the methyl bromoacetate to 10ml by using a diluent, and shaking up the methyl bromoacetate stock solution to obtain the methyl bromoacetate stock solution.
5. The method for detecting methyl bromoacetate according to claim 2, wherein the test solution is prepared by taking 1g of methyl bromoacetate sample, diluting the sample with a diluent to 10ml, and shaking up the sample.
6. The method for detecting methyl bromoacetate according to any one of claims 3 to 5, wherein the diluent is acetonitrile.
7. The method for detecting methyl bromoacetate according to claim 2, wherein the blank solvent is acetonitrile.
8. The method for detecting methyl bromoacetate according to claim 1, wherein the chromatographic conditions in the gas chromatography are as follows:
a chromatographic column: a quartz capillary column with stationary phase 5% phenyl 95% dimethyl polysiloxane;
sample inlet temperature: 135 ℃ and 145 ℃;
a detector: flame ionization detector FID;
detector temperature: 195 ℃ and 205 ℃;
the split ratio is as follows: 3-7: 1;
carrier gas: nitrogen gas;
carrier gas flow: 3.8-4.2 ml/min;
and (3) sample introduction mode: directly feeding a sample;
sample introduction amount: 1 mul;
column box temperature program: the initial column box temperature is kept at 40-50 ℃ for 1min, the temperature is raised to 130 ℃ at 10 ℃/min for 10min, and the temperature is raised to 200 ℃ at 20 ℃/min for 4 min.
9. The method for detecting methyl bromoacetate according to claim 2, further comprising preparing a sample solution, injecting the sample solution into a gas chromatograph, recording a gas chromatogram, and comparing and verifying the chromatogram of the sample solution, the chromatogram of the sample solution and the chromatogram of the control solution.
10. The method for detecting methyl bromoacetate according to claim 9, wherein the preparation method of the sample solution comprises the steps of taking 1g of methyl bromoacetate sample, adding 1ml of methanol stock solution, 1ml of methyl methoxyacetate stock solution, 1ml of methoxyacetate stock solution and 1ml of bromoacetate stock solution, diluting the mixture with a diluent to 10ml, and shaking up to obtain the methyl bromoacetate detection reagent.
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