CN113252831A - Ultra-high performance liquid chromatography analysis method for N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate - Google Patents

Ultra-high performance liquid chromatography analysis method for N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate Download PDF

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CN113252831A
CN113252831A CN202110552180.4A CN202110552180A CN113252831A CN 113252831 A CN113252831 A CN 113252831A CN 202110552180 A CN202110552180 A CN 202110552180A CN 113252831 A CN113252831 A CN 113252831A
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trifluoromethoxy
chloroformyl
phenyl
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CN113252831B (en
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许百红
高洪奎
张晓会
李兰兰
刘亚鲁
许慧斌
王玉莹
朱红玉
张淑艳
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Shandong Jingbo Agrochemical Technology Co ltd
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • 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
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Abstract

The invention relates to the technical field of chemical analysis, in particular to an ultra-high performance liquid chromatography analysis method of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate, (1) preparing a standard solution and a sample solution to be detected, wherein the concentration range of the standard solution and the sample solution is 0.5-2 g/L; (2) setting the detection wavelength to 210nm, sequentially injecting samples according to the sequence of a standard substance, a sample to be detected and the standard substance after the instrument baseline is stable, and respectively calculating the peak area average values of the standard substance solution and the sample solution to be detected; (3) and (3) calculating the content of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected according to an external standard method formula. The analysis method fills the blank of the prior art, has strong specificity, good precision, high recovery rate, high reliability and good repeatability, and is particularly suitable for the quality control of the chemical production process.

Description

Ultra-high performance liquid chromatography analysis method for N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate
Technical Field
The invention relates to the technical field of chemical analysis, in particular to an ultra-high performance liquid chromatography analysis method of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate.
Background
Indoxacarb is a novel, high-efficiency and low-toxicity oxadiazine pesticide developed by DuPont in the United states, and has wide market prospect due to the unique action mechanism.
Methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate is a key intermediate for synthesizing indoxacarb, and because chlorine atoms in chloroformyl contained in the methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate have an electron-withdrawing effect and are relatively active in nature, reactions such as hydrolysis, esterification and the like can occur, most of high performance liquid chromatography can use water as a mobile phase, and therefore, the analysis of the substances by using the high performance liquid chromatography is generally not considered. The current detection method generally adopts a gas chromatography normalization method for detection or a gas chromatography internal standard method for quantitative detection. The invention of China patent CN201210539617.1 discloses a method for analyzing the content of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate, and provides a gas chromatography method which uses diethyl phthalate as an internal standard substance and is tested by means of a capillary chromatographic column and a hydrogen flame ionization detector.
Compared with a hydrogen flame ionization detector of a liquid chromatogram, the ultraviolet detector of the liquid chromatogram does not damage a sample, and the sample does not need to be vaporized at high temperature, so that the stability is higher. And with the application of the small-particle-size and ultra-high performance liquid chromatography column, the liquid chromatography can complete analysis in a short time, and has remarkable advantages.
Therefore, the analysis method for rapidly and stably detecting the content of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate by using the ultra-high performance liquid chromatography is provided, and has important effect and practical significance for ensuring the production of the indoxacarb.
Disclosure of Invention
Aiming at the technical problem of longer content period of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in a gas phase detection method, the invention provides an ultra-high performance liquid chromatography method for analyzing N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate, which fills the blank of the prior art, has strong specificity, good precision, high recovery rate, high reliability and good repeatability, and is particularly suitable for quality control in the chemical production process.
An ultra-high performance liquid chromatography analysis method of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate, comprising the following steps:
(1) respectively dissolving a standard substance and a sample to be detected by using a solvent to prepare a standard substance solution and a sample solution to be detected, wherein the concentration ranges of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the standard substance solution and the sample solution to be detected are 0.5-2 g/L;
(2) setting the detection wavelength of the ultra-high performance liquid chromatography to 210nm, sequentially injecting samples according to the sequence of a standard substance, a sample to be detected and the standard substance after the baseline of the instrument is stable, and respectively calculating the average value of the peak areas of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the solution of the standard substance and the solution of the sample to be detected;
(3) calculating the content of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected according to an external standard method formula, wherein the external standard method formula is as follows:
Figure BDA0003075887000000021
in the formula (I), the compound is shown in the specification,
X1-N-chloroformyl-N- [4- (trifluoromethoxy) phenyl group in sample solution to be tested]Mass fraction of methyl carbamate;
A1-Chloromethyl-N- [4- (trifluoromethoxy) phenyl group in Standard solution]Average of methyl carbamate peak area;
A2-N-chloroformyl-N- [4- (trifluoromethoxy) phenyl group in sample solution to be tested]Average of methyl carbamate peak area;
m1-the quality of the standard;
m2-the mass of the sample to be tested;
P1-Chloromethyl-N- [4- (trifluoromethoxy) phenyl group in Standard substance]Mass fraction of methyl carbamate.
Further, in the step (1), acetonitrile is used for dissolving the standard substance and the sample to be detected. Acetonitrile is more inert than methanol, and the sample is more stable by using acetonitrile as a solvent.
Further, the step (2) uses a C18 reversed phase chromatographic column, the temperature of the chromatographic column is 30-40 ℃, and the mobile phase is a mixed system of acetonitrile and water. The temperature range of 30-40 ℃ is in the using temperature range of the chromatographic column and is easy to control, the constant temperature of the chromatographic column is controlled, the stability of retention time is ensured, and the repeatability of sample detection is improved.
Further, the length of the chromatographic column in the step (2) is 100mm, the inner diameter of the chromatographic column is 3-4.6mm, and the particle size is 1.8-2.7 μm.
Further, the volume ratio of acetonitrile to water in the mobile phase in the step (2) is 7-5: 3-5, in the range of the flow ratio, the total machine time of the standard sample and the sample is ensured to be less than 10min, and the separation degree of the standard sample and the solvent and impurities is ensured.
Further, the flow rate of the mobile phase in the step (2) is 1.0-1.5 mL/min. The flow rate is less than 1.0mL/min, the analysis time is increased, and chromatographic peak broadening can be caused; flow rates >1.5mL/min, while not significantly affecting the separation, can cause the chromatograph system to be over-pressurized.
Further, the sample volume of each injection sample in the step (2) is 5 μ L.
Further, the step (2) is specifically as follows:
using a C18 reversed phase chromatographic column, wherein the length of the chromatographic column is 100mm, the inner diameter of the chromatographic column is 3mm, the particle size is 2.7 mu m, the temperature of the chromatographic column is 40 ℃, and the volume ratio of a mobile phase is 6: 4, the flow rate of a mobile phase is 1.5mL/min, the detection wavelength of the ultra-high performance liquid chromatography is set to 210nm, samples are sequentially injected according to the sequence of a standard substance, a sample to be detected and the standard substance after the baseline of the instrument is stable, the volume of the sample injected each time is 5 mu L, and the average value of the peak areas of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the standard substance solution and the sample solution to be detected is respectively calculated.
The 2.7 mu m particle size chromatographic column is the most common type in the commercial ultra-high performance liquid chromatographic column at present, and compared with the conventional chromatographic columns with particle sizes of 4 mu m and 5 mu m, the ultra-high performance chromatographic column with the type has higher theoretical plate number and better separation degree; the column length of a conventional liquid chromatographic column is usually more than 150mm, the liquid chromatographic column with small particle size is usually less than 100mm, and the inner diameter is thinner, so that the column volume is smaller than that of the conventional liquid chromatographic column, the dead time of the chromatographic column with small column volume is shorter under the same detection condition, and the method is particularly important for shortening the detection time; the chromatographic peak area obtained by the chromatographic column with small volume is higher, and the detection sensitivity is also higher. If a column with a smaller particle size is selected, the column pressure will rise significantly and the equipment requirements will be higher.
The beneficial effect of the invention is that,
the brand new method for detecting the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate fills the blank of the prior art in the corresponding field, the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate contains chloroformyl groups, and the property is relatively active, but when the method is used for analysis, the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate cannot be hydrolyzed;
the concentration of the solution is limited to be 0.5-2g/L, and within the concentration range, the standard sample and the sample can be directly weighed into the volumetric flask without operations such as transfer, dilution and the like, so that the operation is simplified, and the analysis time is saved;
the detection wavelength is limited to 210nm, N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate has better ultraviolet absorption in the wavelength range, and the linear range of a sample under the wavelength is wider, the peak area size is proper, the absorption is stable, and the improvement of the detection precision and the stability is facilitated;
the detected N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate has stable and accurate mass fraction, can realize complete separation of impurities, a position to be detected and a solvent peak, has good chromatographic peak shape, stable retention time, accurate integral calculation result, good repeatability and high reliability of the obtained result, has wide linear range through linear verification, can accurately analyze the content by adopting a single standard comparison method, and does not need to make a multi-point correction curve;
compared with other detection methods, the method is simpler and faster in operation, the standard substance and the sample are only required to be weighed and then dissolved to a constant volume, the operation can be carried out on the machine, the preparation and the removal of an internal standard solution are not required, the ultra-high performance liquid chromatography and the small-particle-size chromatographic column are used, the time sharing time is short, the single on-machine operation time of the standard substance and the sample can be controlled to be about 2min, the on-machine operation of the sample and the standard substance can be completed only within about 10min, the analysis time is greatly shortened, and the method is particularly suitable for the detection of process control;
in conclusion, the analysis method disclosed by the invention not only ensures the accuracy of the detection result, but also ensures the timeliness of the detection result, and provides powerful data support for the production of indoxacarb.
Drawings
In order to more clearly illustrate the embodiments or technical solutions in the prior art of the present invention, the drawings used in the description of the embodiments or prior art will be briefly described below, and it is obvious for those skilled in the art that other drawings can be obtained based on these drawings without creative efforts.
FIG. 1 is a chromatogram of the standard solution in example 1;
FIG. 2 is a chromatogram of a sample solution to be tested in example 1;
FIG. 3 is a chromatogram of the standard solution in example 2;
FIG. 4 is a chromatogram of a sample solution to be tested in example 2;
FIG. 5 is a chromatogram of the standard solution in example 3;
FIG. 6 is a chromatogram of a sample solution to be tested in example 3;
FIG. 7 is an acetonitrile solution chromatogram of methyl acetate in example 3;
FIG. 8 is a chromatogram of a sample to be tested in comparative example 1 after being left for 2 hours in a methanol solution;
FIG. 9 is a mass spectrum of impurities generated when the methanol solution of the sample to be tested is left for 2 hours in comparative example 1;
FIG. 10 is a graph showing the linear relationship in test example 4;
FIG. 11 is a UV spectrum of methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate in comparative example 2;
FIG. 12 is a graph showing the linear relationship with 195nm as the detection wavelength in comparative example 2;
FIG. 13 is a graph showing the linear relationship with the detection wavelength of 220nm in comparative example 2;
wherein in FIGS. 1-8, the abscissa represents time and the ordinate represents absorbance; in fig. 9, the abscissa represents the charge-to-mass ratio and the ordinate represents the abundance; in FIGS. 10, 12, and 13, the abscissa represents the concentration of the standard solution (in g/L), and the ordinate represents the average peak area; in fig. 11, the abscissa represents wavelength and the ordinate represents absorbance.
Detailed Description
In order to make those skilled in the art better understand the technical solution of the present invention, the technical solution in the embodiment of the present invention will be clearly and completely described below with reference to the drawings in the embodiment of the present invention, and it is obvious that the described embodiment is only a part of the embodiment of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A sample of methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate is analyzed for its content by a method comprising the steps of:
(1) accurately weighing N-chloroformyl-N- [4- (trifluoromethoxy) phenyl]Placing 0.0496g of methyl carbamate standard substance into a 50mL volumetric flask, adding 45mL of acetonitrile, oscillating to dissolve, diluting to a scale with the acetonitrile to obtain a standard substance solution for later use, wherein the standard substance solution contains N-chloroformyl-N- [4- (trifluoromethoxy) phenyl]Mass fraction P of methyl carbamate1＝99.5％；
Accurately weighing 0.0541g of a sample to be detected, placing the sample to be detected in a 50mL volumetric flask, adding 45mL of acetonitrile, after oscillating and dissolving, diluting the sample to be detected to a scale with the acetonitrile to obtain a sample solution to be detected for later use;
(2) adopting an ultra-high performance liquid chromatograph, wherein a chromatographic column is an EC-C18 reversed-phase chromatographic column, the length of the chromatographic column is 100mm, the inner diameter of the chromatographic column is 3.0mm, and the particle size of the chromatographic column is 2.7 mu m; the temperature of the chromatographic column is 40 ℃; the mobile phase is 6: 4, a mixed system of acetonitrile and water; the flow rate of the mobile phase is 1.5 mL/min; the detection wavelength was set to 210 nm;
after the baseline of the instrument is stable, samples are sequentially injected according to the sequence of a standard substance, a sample to be detected and the standard substance, the volume of the sample injected each time is 5 mu L, the average value of the peak areas of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the solution of the standard substance and the solution of the sample to be detected is respectively calculated, the detection spectrum is shown in figure 1 and figure 2, the position of 1.120min in figure 1 corresponds to the chromatographic peak of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the standard substance, and the position of 1.123min in figure 2 corresponds to the chromatographic peak of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected; the test data are shown in table 1 below:
table 1 example 1 test results
Figure BDA0003075887000000071
(3) Calculating the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected according to an external standard method formula which is as follows,
Figure BDA0003075887000000072
in the formula (I), the compound is shown in the specification,
X1-chloroformyl-N- [4- (trifluoromethoxy) phenyl group in sample to be tested]Mass fraction of methyl carbamate;
A1-Chloromethyl-N- [4- (trifluoromethoxy) phenyl group in Standard solution]Average of methyl carbamate peak area;
A2-N-chloroformyl-N- [4- (trifluoromethoxy) phenyl group in sample solution to be tested]Average of methyl carbamate peak area;
m1-the quality of the standard;
m2-the mass of the sample to be tested;
P1-Chloromethyl-N- [4- (trifluoromethoxy) phenyl group in Standard substance]Mass fraction of methyl carbamate;
and calculating to obtain the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected to be 99.3%.
Example 2
A sample of methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate is analyzed for its content by a method comprising the steps of:
(1) accurately weighing N-chloroformyl-N- [4- (trifluoromethoxy) phenyl]Placing 0.0385g of methyl carbamate standard substance into a 50mL volumetric flask, adding 45mL of acetonitrile, oscillating to dissolve, diluting with acetonitrile to a scale to obtain a standard substance solution for later use, wherein the standard substance solution is N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl]Mass fraction P of methyl carbamate1＝99.5％；
Accurately weighing 0.0407g of a sample to be detected, placing the sample to be detected in a 50mL volumetric flask, adding 45mL of acetonitrile, after oscillating and dissolving, diluting the sample to be detected to a scale with the acetonitrile to obtain a sample solution to be detected for later use;
(2) adopting a high performance liquid chromatograph, wherein a chromatographic column is an HPH-C18 reversed phase chromatographic column, the length of the chromatographic column is 100mm, the inner diameter of the chromatographic column is 3.0mm, and the particle size of the chromatographic column is 2.7 mu m; the temperature of the chromatographic column is 35 ℃; the mobile phase is 7: 3, a mixed system of acetonitrile and water; the flow rate of the mobile phase is 1.0 mL/min; the detection wavelength was set to 210 nm;
after the baseline of the instrument is stable, samples are sequentially injected according to the sequence of a standard substance, a sample to be detected and the standard substance, the volume of the sample injected each time is 5 muL, the average value of the peak areas of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the solution of the standard substance and the solution of the sample to be detected is respectively calculated, a detection spectrum is shown in a figure 3 and a figure 4, the position of 1.252min in the figure 3 corresponds to the chromatographic peak of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the standard substance, and the position of 1.256min in the figure 4 corresponds to the chromatographic peak of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected; the test data are shown in table 2 below:
table 2 example 2 test results
Figure BDA0003075887000000081
(3) And (3) calculating the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected according to an external standard method formula, wherein the external standard method formula is the same as the example 1, and the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected is calculated to be 98.3%.
Example 3
In the process of research and development of a small scale, N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate is prepared into a solution methyl acetate solution to carry out indoxacarb synthesis reaction, and the prepared methyl acetate solution is subjected to N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate content detection, wherein the method comprises the following steps:
(1) accurately weighing N-chloroformyl-N- [4- (trifluoromethoxy) phenyl]Placing 0.0425g of methyl carbamate standard substance into a 50mL volumetric flask, adding 45mL of acetonitrile, oscillating to dissolve, diluting to a scale with the acetonitrile to obtain a standard substance solution for later use, wherein N-chloromethyl in the standard substance isacyl-N- [4- (trifluoromethoxy) phenyl group]Mass fraction P of methyl carbamate1＝99.5％；
Accurately weighing 0.1156g of a sample to be detected, placing the sample to be detected in a 50mL volumetric flask, adding 45mL of acetonitrile, after oscillating and dissolving, diluting the sample to be detected to a scale with the acetonitrile to obtain a sample solution to be detected for later use;
(2) adopting a high performance liquid chromatograph with a diode array detector, wherein the chromatographic column is an EC-C18 reversed phase chromatographic column, the length of the chromatographic column is 100mm, the inner diameter of the chromatographic column is 3.0mm, and the particle size of the chromatographic column is 1.8 mu m; the temperature of the chromatographic column is 30 ℃; the mobile phase is 5: 5 of a mixed system of acetonitrile and water; the flow rate of the mobile phase is 1.5 mL/min; the detection wavelength was set to 210 nm;
after the baseline of the instrument is stable, samples are sequentially injected according to the sequence of a standard substance, a sample to be detected, the sample volume of each sample injection is 5 mu L, the average value of the peak areas of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the solution of the standard substance and the solution of the sample to be detected is respectively calculated, the detection spectrum is shown in a figure 5 and a figure 6, the position of 2.037min in the figure 5 corresponds to the chromatographic peak of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the standard substance, and the position of 2.042min in the figure 6 corresponds to the chromatographic peak of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected; the test data are shown in table 3 below:
table 3 example 3 test results
Figure BDA0003075887000000091
(3) And (3) calculating the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected according to an external standard method formula, wherein the external standard method formula is the same as the example 1, and the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected is calculated to be 35.5%.
In order to verify that no impurity chromatographic peak consistent with the peak position of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate exists in the methyl acetate, the methyl acetate is prepared into a 2mg/mL acetonitrile solution for analysis, and then the feasibility of the method is confirmed, wherein the detection spectrum is shown in figure 7, and the figure 7 has no chromatographic peak near 2.0min, so that the methyl acetate does not cause interference on detection.
Test example 1 stability test
Since methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate contains acyl chloride groups and is relatively active in nature, in order to verify the stability of the methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate in a solvent and a mobile phase, the standard solution in example 1 is taken as a subject to be examined, and is analyzed once at intervals of a certain time at room temperature for 6 times, and simultaneously, the peak area is recorded, and the analysis conditions are the same as in example 1. The results are shown in the following table 4, the retention time of chromatographic peaks is stable, the RSD is less than 1% when comparing peak areas, which indicates that the analysis method of the present invention has good stability.
TABLE 4 stability test results
Figure BDA0003075887000000101
Comparative example 1
About 52.5mg of the sample in example 1 was weighed, placed in a 50mL volumetric flask, added with 45mL of methanol, dissolved by shaking, diluted to the scale with methanol, analyzed once every certain time at room temperature for 6 times, and simultaneously the peak area was recorded, the stability of the peak area was examined, and the chromatographic conditions were the same as in test example 1. As shown in table 5 below, although the retention time of the chromatographic peak was stable, the comparative peak area was found to be stable between 0 and 1h, but the chromatographic peak area tended to decrease significantly after 2h, unlike in the case of the verification example 1. FIG. 8 is a liquid chromatogram of a sample analyzed after being left for 2h, an impurity peak is added at 1.400min, FIG. 9 is a mass spectrogram of the impurity peak, and the peak is a product peak of the impurity structure of substituting the chlorine in the chloroformyl group in the methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate by the methoxy group, which indicates that the sample is left in methanol for a period of time and then undergoes an esterification reaction with the methanol.
TABLE 5 stability test results of the samples in methanol
Figure BDA0003075887000000111
It was found from the data of comparative test example 1 and comparative example 1 that the stability of methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate in acetonitrile was better, and therefore it was more appropriate to select acetonitrile as the solvent.
Test example 2 precision test
Taking the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate sample in example 2 as an investigation object, weighing 0.0385g of standard substance and five parallel samples to be tested, respectively placing the samples in a 50mL volumetric flask, adding 45mL of acetonitrile to oscillate and dissolve, diluting the samples to the scale with acetonitrile, preparing a standard substance solution and a sample solution to be tested, respectively injecting samples according to the sequence of the standard substance solution, the sample solution to be tested, the sample to be tested and the standard substance solution, calculating the mass fraction of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the five parallel samples to be tested, and analyzing conditions are the same as example 2. The results are shown in table 6 below, and comparing the mass fraction of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamic acid methyl ester, the RSD is less than 1%, indicating that the analytical method of the present invention has good precision.
TABLE 6 results of precision test
Figure BDA0003075887000000112
Figure BDA0003075887000000121
Test example 3 recovery test
Taking the sample of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the example 1, accurately preparing five methyl acetate solutions with different concentrations, and comparing the detected content with the theoretical content to perform a recovery rate experiment;
the analysis conditions were: adopting a high performance liquid chromatograph with a diode array detector, wherein a chromatographic column is an HPH-C18 reversed phase chromatographic column, the length of the chromatographic column is 100mm, the inner diameter of the chromatographic column is 3.0mm, and the particle size of the chromatographic column is 1.8 mu m; the temperature of the chromatographic column is 40 ℃; the mobile phase is 5: 5, the flow rate of a mobile phase is 1.5 mL/min; setting the detection wavelength of the high performance liquid chromatography to 210 nm;
after the baseline of the instrument is stable, samples are sequentially injected according to the sequence of the standard substance, the sample to be detected, the standard substance and the sample to be detected, the volume of the sample injected each time is 5 mu L, the average value of the peak areas of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the standard substance solution and the sample solution to be detected is calculated respectively, the results are shown in the following table 7, the recovery rates are all 99-101%, the average recovery rate is 99.6%, and the experimental recovery rate meets the requirements.
TABLE 7 recovery test results
Figure BDA0003075887000000122
Figure BDA0003075887000000131
Test example 4 Linear test
Weighing a series of standard substances with different masses, respectively placing the standard substances in 50mL volumetric flasks, adding 45mL acetonitrile, oscillating and dissolving, diluting to a scale with the acetonitrile, observing the relation between the peak area and the solution concentration after sample injection, and analyzing under the same conditions as in example 1. The results are shown in table 8 below and fig. 10, and the correlation coefficient is 1.00, which indicates that the analysis method provided by the present invention is linear and meets the requirements.
TABLE 8 results of the Linear test
Figure BDA0003075887000000132
Comparative example 2
Scanning N-chloroformyl-N- [4- (trifluoromethoxy) phenyl group by liquid chromatography diode array detector]The ultraviolet spectrum of methyl carbamate is shown in FIG. 11, and N-chloroformyl-N- [4- (trifluoromethoxy) phenyl]Amino-methylLambda of methyl ester of acidmax195nm and essentially no absorption at wavelengths greater than 230 nm. The invention selects the wavelength of 210nm as the analysis wavelength and carries out linear verification, because the slope of the 210nm on the absorption curve is lower, the influence of the instrument condition and the like is smaller, the absorption is more stable, and the wavelength analysis is used for analyzing the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl group]In the case of methyl carbamate, the peak area size is suitable and suitable as an analysis wavelength.
Under the conditions of test example 4, linearity verification was performed at wavelengths of 195nm and 220nm, respectively, and the results are shown in tables 9 to 10 and FIGS. 12 to 13. As can be seen from Table 9 and FIG. 11, the peak area obtained by detection is too large due to the large absorption at wavelength of 195nm, and the last two concentration points are obviously not in the linear range; as can be seen from Table 10 and FIG. 12, although the linear correlation coefficient R at a wavelength of 220nm was obtained2The value is also larger than 0.99, but compared with a linear equation under the wavelength of 210nm, the linear correlation coefficient is small, the intercept is very large, if the single standard comparison method is adopted for sample analysis, the error is large, and only a multi-point standard curve can be drawn for sample analysis each time.
TABLE 9195 nm wavelength Linear test results
Figure BDA0003075887000000141
TABLE 10220 nm wavelength Linear test results
Figure BDA0003075887000000142
It can be seen from the above test examples 1-4 and comparative examples 1-2 that the method for analyzing the content of methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate provided by the present invention has high accuracy and good operability, and can be widely applied to the analysis and detection of the content of methyl N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] carbamate.
Although the present invention has been described in detail by referring to the drawings in connection with the preferred embodiments, the present invention is not limited thereto. Various equivalent modifications or substitutions can be made on the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and these modifications or substitutions are within the scope of the present invention/any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention.

Claims (8)

  1. An ultra-high performance liquid chromatography analysis method of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate, which is characterized by comprising the following steps:
    (1) respectively dissolving a standard substance and a sample to be detected by using a solvent to prepare a standard substance solution and a sample solution to be detected, wherein the concentration ranges of N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the standard substance solution and the sample solution to be detected are 0.5-2 g/L;
    (2) setting the detection wavelength of the ultra-high performance liquid chromatography to 210nm, sequentially injecting samples according to the sequence of a standard substance, a sample to be detected and the standard substance after the baseline of the instrument is stable, and respectively calculating the average value of the peak areas of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the solution of the standard substance and the solution of the sample to be detected;
    (3) and (3) calculating the content of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate in the sample to be detected according to an external standard method formula.
  2. 2. The ultra high performance liquid chromatography analysis method according to claim 1, wherein the acetonitrile is used in the step (1) to dissolve the standard substance and the sample to be tested.
  3. 3. The ultra high performance liquid chromatography analysis method of claim 1, wherein the C18 reverse phase chromatographic column is used in the step (2), the temperature of the chromatographic column is 30-40 ℃, and the mobile phase is a mixed system of acetonitrile and water.
  4. 4. The ultra high performance liquid chromatography analysis method according to claim 1, wherein the column length of the chromatography column of step (2) is 100mm, the inner diameter of the column is 3 to 4.6mm, and the particle diameter is 1.8 to 2.7 μm.
  5. 5. The ultra performance liquid chromatography analysis method of claim 1, wherein the volume ratio of acetonitrile to water in the mobile phase of step (2) is 7-5: 3-5.
  6. 6. The ultra high performance liquid chromatography analysis method according to claim 1, wherein the flow rate of the mobile phase in the step (2) is 1.0 to 1.5 mL/min.
  7. 7. The ultra high performance liquid chromatography analysis method according to claim 1, wherein the sample volume per sample injection in step (2) is 5 μ L.
  8. 8. The ultra high performance liquid chromatography analysis method according to claim 1, wherein the step (2) is specifically:
    using a C18 reversed phase chromatographic column, wherein the length of the chromatographic column is 100mm, the inner diameter of the chromatographic column is 3mm, the particle size is 2.7 mu m, the temperature of the chromatographic column is 40 ℃, and the volume ratio of a mobile phase is 6: 4, the flow rate of a mobile phase is 1.5mL/min, the detection wavelength of the ultra-high performance liquid chromatography is set to 210nm, samples are sequentially injected according to the sequence of a standard substance, a sample to be detected and the standard substance after the baseline of the instrument is stable, the volume of the sample injected each time is 5 mu L, and the average value of the peak areas of the N-chloroformyl-N- [4- (trifluoromethoxy) phenyl ] methyl carbamate of the standard substance solution and the sample solution to be detected is respectively calculated.
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