Gas chromatography-mass spectrometry analysis method of dimethyl carbamoyl chloride

Abstract

The invention discloses a gas chromatography-mass spectrometry analysis method of dimethyl carbamoyl chloride. The method comprises the following steps: S1, setting a chromatographic column; s2, selecting carrier gas, and adjusting the purity and flow velocity of the carrier gas; s3, preparing solutions: preparing a DMCC contrast solution, a test solution and a system adaptive solution; s4, starting a GC-MS system: setting a heating program: keeping the initial temperature at 60-80 DEG C for 2 minutes, then heating to 250 DEG C at the speed of 15-20 DEG C / min, and keeping the temperature for 6-10 minutes; setting the collected molecular weight to be 107, selecting electron ionization (EI) as an ion source type, and setting the temperature of a sample inlet, the temperature of the ion source and the temperature of an ion transmission line; s5, sample injection: sucking the sample solution or the contrast solution by using a microsyringe; a sample is carefully injected into a GC sample inlet, and data is obtained after analysis. The gas chromatography-mass spectrometry analysis method of the dimethylaminoformyl chloride can directly detect the DMCC in the compound, does not need derivation, and is relatively low in detection limit, short in detection time and convenient to operate.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of gas chromatography-mass spectrometry detection method, in particular to a gas chromatography-mass spectrometry analysis method for dimethyl carbamoyl chloride. BACKGROUND

[0002] As a genotoxic impurity, dimethyl carbamoyl chloride (DMCC) has few methods for detecting DMCC. There are three known methods for detecting DMCC in the literature, 1) gas phase detection method for detecting DMCC and its related substances; 2) gas chromatography-mass spectrometry for detecting DMCC in sodium glycopyrronium; 3) N,N-dimethyl carbamate is generated by derivatization of DMCC and ethanol, and the generation and hydrolysis of DMCC in the Vilsmeier reaction are detected by gas chromatography-mass spectrometry using selected ion mode. These are the current methods for detecting dimethyl carbamoyl chloride, which use gas chromatography and gas chromatography-mass spectrometry. The gas phase detection method detects DMCC and its related substances, with a quantitative limit of 10.126 μg / ml, and the sensitivity cannot meet the requirements; the gas chromatography-mass spectrometry detects DMCC in sodium glycopyrronium, using ether as the solvent, which is a drug precursor, so its use is limited; the derivatization method detects the generation and hydrolysis of DMCC, which may cause side reactions and loss of target substances, and the pretreatment time is relatively long, which has certain limitations. The existing DMCC detection methods have significant shortcomings in sensitivity, ease of operation and compliance, and there is an urgent need to develop direct, high-sensitivity and environmentally friendly trace analysis technology. SUMMARY

[0003] The present application provides a gas chromatography-mass spectrometry analysis method for dimethyl carbamoyl chloride, which can integrate advanced instrument technology and simplify the pretreatment process, provide a reliable solution for the quality control of dimethyl carbamoyl chloride (DMCC), and promote the standardization process of drug research and production.

[0004] The present application first provides a gas chromatography-mass spectrometry analysis method for dimethyl carbamoyl chloride, characterized by comprising the following steps:

[0005] S1 sets up a chromatographic column;

[0006] S2 selects carrier gas and adjusts its purity and flow rate;

[0007] S3 configures solutions: DMCC control solution, test sample solution, and system suitability solution;

[0008] S4 starts the GC-MS system:

[0009] Temperature programming: initial temperature 60-80℃ for 2 minutes, then increase the temperature to 250℃ at a rate of 15-20℃ / min, and keep the temperature for 6-10 minutes;

[0010] Set the acquisition molecular weight as 107, select electron ionization (EI) as the ion source type, and set the inlet temperature, ion source temperature and ion transmission line temperature;

[0011] S5 sample injection:

[0012] Use a microsyringe to suck the sample solution or the control solution; carefully inject the sample into the GC inlet, and obtain data after analysis.

[0013] The application also provides the following optimization scheme:

[0014] Preferably, the chromatographic column in S1 is DB-624, with a specification of 30m x 0.32mm x 1.8μm.

[0015] Preferably, the carrier gas in S2 is nitrogen, with a flow rate of 1.5ml / min.

[0016] Preferably, the concentration of the DMCC control solution in S3 is 0.3μg / ml.

[0017] Preferably, the concentration of the test sample solution in S3 is 100mg / ml.

[0018] Preferably, the inlet temperature, ion source temperature and ion transmission line temperature in S4 are all 250℃.

[0019] Preferably, the split ratio in S4 is set as 50:1.

[0020] Preferably, the preparation method of the DMCC control solution in S3 is as follows: accurately weigh 30mg of DMCC into a 10ml volumetric flask, add appropriate diluent to make up to 10ml, and shake well; take 1ml from the above solution into another 100ml volumetric flask, and again make up to 100ml with diluent, and shake well; repeat this step once to obtain the DMCC control solution with a final concentration of 0.3μg / ml.

[0021] Preferably, the diluent is one of dichloromethane, toluene or acetonitrile.

[0022] Preferably, the preparation method of the test sample solution is as follows: accurately weigh 1g of the test sample into a 10ml volumetric flask, add diluent to make up to 10ml, and shake well.

[0023] The detailed settings of the temperature rising procedure are as follows: the initial temperature is 80 DEG C and is kept for 2 minutes, then the temperature is raised to 250 DEG C at a speed of 20 DEG C / min, and is kept at this temperature for 6 minutes, and the total running time is 16.5 minutes.

[0024] The acquisition molecular weight is set to 107, the electron ionization (EI) is selected as the ion source type, and the ion source temperature and the ion transmission line temperature are both set to 250 DEG C.

[0025] The split ratio is set to 50:1.

[0026] Sample injection:

[0027] 1 ul of the sample solution or the control solution is taken by using a microsyringe, and plastic droppers are avoided to prevent pollution. The sample is carefully injected into the GC injection port, and data analysis is performed after detection.

[0028] The beneficial effects of the present application are as follows:

[0029] Compared with the prior art, the gas chromatography mass spectrometry analysis method of dimethylcarbamoyl chloride of the present application can directly detect DMCC in the compound without derivation, has a lower detection limit, a shorter detection time, and convenient operation.

[0030] The gas chromatography mass spectrometry analysis method of dimethylcarbamoyl chloride of the present application has good separation effect, and through gradual temperature rising, effective separation of DMCC and related impurities can be realized; the moderate temperature rising rate and the reasonable holding time reduce peak broadening, and improve detection sensitivity. The chromatographic column is cleaned in the high-temperature holding stage, the influence of residues on subsequent analysis is reduced, and the durability is strong. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 The blank solvent peak chromatogram of Example 1 of the present application is shown in Figure 1.

[0032] Figure 2 The chromatogram of the target compound (DMCC) of Example 1 of the present application is shown in Figure 2.

[0033] Figure 3 The linear graph of the concentration and the peak area of DMCC detection of the present application is shown in Figure 3.

[0034] Figure 4 The chromatogram of the target compound (DMCC) of the present application using toluene as a diluent is shown in Figure 4.

[0035] Figure 5 The chromatogram of the target compound (DMCC) of the present application using acetonitrile as a diluent is shown in Figure 5. DETAILED DESCRIPTION

[0036] In order for those skilled in the art to better understand the technical solutions of the application, the application will be further described in detail below with reference to the specific embodiments.

[0037] At present, three detection methods of DMCC are known in the literature, which are as follows:

[0038] 1) The detection method of DMCC and its related substances by gas phase detection method is as follows:

[0039] Detector: hydrogen flame ionization detector

[0040] Detector temperature: 240℃

[0041] Chromatographic column: CP-Volamine, 30m x 0.32mm

[0042] Injection port temperature: 190℃

[0043] Carrier gas: nitrogen

[0044] Carrier gas flow rate: 1.4ml / min

[0045] Injection mode: split injection

[0046] Split ratio: 21:1

[0047] Injection volume: 1μl

[0048] Temperature program: 35℃ for 5min, then increased to 180℃ at a rate of 8℃ / min for 3min, and then increased to 200℃ at a rate of 40℃ / min for 10min

[0049] The limit of quantification is 10.126μg / ml, and the diluent is acetonitrile.

[0050] 2) The detection method of DMCC in sodium glycopyrrate by gas phase-mass spectrometry is as follows:

[0051] Chromatographic column: VF-624ms, 30m x 0.25mm, 1.4μm

[0052] Initial column temperature: 40℃

[0053] Carrier gas: helium

[0054] Column flow rate: 1.5ml / min

[0055] Mass spectrometry detection mode: selected ion mode (SIM)

[0056] Target ion m / z: 107

[0057] The solvent used is diethyl ether, and the limit of quantification is 8.08ng / ml.

[0058] 3) N,N-dimethylcarbamate based on DMCC and ethanol derivatization, and the use of selected ion mode by gas-mass spectrometry to detect the generation and hydrolysis of DMCC in the Wilmsmeier reaction, detection method:

[0059] Chromatographic column: DB-1701, 30 m x 0.25 mm, 0.25 μm

[0060] Carrier gas: helium

[0061] Flow rate: 1.0 ml / min

[0062] Split ratio: 50:1

[0063] Detector temperature: 250°C

[0064] Temperature program: 40°C for 2 min, 10°C / min to 130°C, 40°C / min to 300°C, hold for 5 min

[0065] Acquisition mode: Selected ion monitoring

[0066] Target ion acquisition time: 6.0-10.5 min

[0067] Target ion m / z: 72.0, 89.0 and 117.0 (quantitative)

[0068] Naphthalene acquisition time: 10.5-20.2 min

[0069] Naphthalene m / z: 64.0, 102.0, 128.0 (quantitative)

[0070] Dwell time: 100 ms

[0071] Derivation process: Weigh 0.5 g of sample into a 5 ml test tube containing ethanol (1 ml), heat to 70°C, continuously heat, and put DMCC (0.5 ml) into it, after one hour, cool to room temperature. Add saturated sodium bicarbonate (1-2 ml) and water (1-2 ml) to the test tube, adjust the pH to 8-9, extract with dichloromethane containing 50 ppm naphthalene, dry the organic phase with anhydrous sodium sulfate, and detect. The limit of quantification is 0.35 μg / ml.

[0072] Among the above three detection methods, the gas phase detection method detects DMCC and its related substances, with a limit of quantification of 10.126 μg / ml, and the sensitivity cannot meet the requirements; the gas-mass spectrometry detection of DMCC in sodium glycopyrronium uses ether as the solvent, and ether is a chemical that can be easily made into a drug, so its use is limited; the derivation method for detecting the generation and hydrolysis of DMCC will cause side reactions and loss of target substances, and the pretreatment time is relatively long, which has certain limitations.

[0073] The application adopts gas chromatography-mass spectrometry to analyze dimethyl carbamoyl chloride, and the detailed operation steps are as follows:

[0074] S1 sets the chromatographic column;

[0075] The chromatographic column is set to DB-624, with a specification of 30 m x 0.32 mm, 1.8 μm; and it is confirmed that the gas chromatography-mass spectrometer (GC-MS) has been correctly installed and debugged.

[0076] S2 selects the carrier gas and adjusts its purity and flow rate;

[0077] The carrier gas is nitrogen, and its purity and flow rate are ensured to meet the requirements. The flow rate is 1.5 ml / min.

[0078] S3 configures the solution: configure the DMCC control solution, the test sample solution, and the system adaptability solution;

[0079] The DMCC control solution (0.3 μg / ml) is prepared by accurately weighing 30 mg of DMCC into a 10 ml volumetric flask, adding an appropriate amount of diluent (such as dichloromethane) to make up the volume, and shaking well; 1 ml of the above solution is transferred to another 100 ml volumetric flask, which is again diluted with diluent to make up the volume, and shaken well; this step is repeated once to obtain a DMCC control solution with a final concentration of 0.3 μg / ml.

[0080] The test sample solution (100 mg / ml) is prepared by accurately weighing 1 g of the test sample into a 10 ml volumetric flask, adding diluent to make up the volume, and shaking well.

[0081] The system adaptability solution is prepared by adding 1 g of the test sample into a 10 ml volumetric flask, and then using the DMCC control solution to make up the volume and shake well.

[0082] S4 starts the GC-MS system:

[0083] Turn on the instrument power, and preheat the equipment to the specified temperature according to the manufacturer's operation manual; and tune the gas chromatography instrument performance (ISQ Dashboard).

[0084] Set the temperature rising program: the initial temperature is 80℃, which is maintained for 2 minutes, then the temperature is raised to 250℃ at a speed of 20℃ / min, and maintained at this temperature for 6 minutes; the total running time is 16.5 minutes.

[0085] Set the acquisition molecular weight to 107, select electron ionization (EI) as the ion source type, and set the injection port temperature, ion source temperature, and ion transmission line temperature to 250℃; the split ratio is set to 50:1.

[0086] S5 sample injection:

[0087] Using a microsyringe to take 1 μl of sample solution or control solution, avoid using plastic dropper to prevent pollution; Carefully inject the sample into the GC injection port, get the data after analysis.

[0088] Data analysis:

[0089] Collect data and generate chromatogram and mass spectrum.

[0090] Compare the response of the blank solvent peak and the target compound (DMCC) to confirm no interference.

[0091] The temperature program is the key point of the invention technology, the following is the detailed exposition of the temperature program.

[0092] 1. Design logic of temperature program

[0093] The temperature program is:

[0094] Initial temperature: 80℃, hold for 2 minutes

[0095] Temperature rate: rise to 250℃ at 20℃ / min

[0096] Final temperature: 250℃, hold for 6 minutes

[0097] Total running time: 16.5 minutes

[0098] This design combines the physicochemical properties of volatile compounds, the separation ability of the chromatographic column, and the separation requirements of the target compound (DMCC) and impurities.

[0099] 2. Initial temperature and holding time (80℃, hold for 2 minutes)

[0100] Principle:

[0101] 80℃ is a relatively low initial temperature, the purpose is to let the low boiling point or volatile compounds start to separate at the inlet of the chromatographic column.

[0102] Hold for 2 minutes is to ensure that these low boiling point compounds can fully enter the chromatographic column and start to separate, while reducing the peak broadening or tailing phenomenon caused by premature sample loss.

[0103] Effect:

[0104] Helps to separate low boiling point impurities that may interfere with detection.

[0105] Ensures that DMCC and other high boiling point compounds will not be "taken out" at the initial injection stage, thus avoiding peak overlap.

[0106] 3. Temperature rate (20℃ / min)

[0107] Principle:

[0108] 20℃ / min is a moderate ramp rate that balances separation efficiency with analysis time.

[0109] Too fast a ramp rate can cause poor peak shape (e.g., broadening or tailing), while too slow a ramp rate can extend analysis time and reduce efficiency.

[0110] Purpose:

[0111] Ramping the column temperature gradually allows compounds of different boiling points to elute from the column in sequence, resulting in good separation.

[0112] For a moderately volatile compound like DMCC, a ramp rate of 20℃ / min ensures effective separation from other impurities (e.g., matrix components or other related substances).

[0113] 4. Final temperature and hold time (250℃, hold for 6 minutes)

[0114] Principle:

[0115] 250℃ is a high temperature designed to ensure that all volatile compounds, including high-boiling impurities, elute completely from the column.

[0116] Holding for 6 minutes allows for thorough column cleaning, preventing residual interference with subsequent analyses.

[0117] Purpose:

[0118] The high-temperature hold phase elutes any high-boiling impurities that may be trapped in the column, preventing them from affecting the next analysis.

[0119] Cleaning the column helps extend its lifespan and ensures stability for each analysis.

[0120] 5. Special considerations for DMCC

[0121] DMCC is a moderately volatile compound with a small molecular weight (107 Da) and some thermal stability.

[0122] An initial temperature of 80℃ is sufficient to introduce DMCC into the column, while a ramp rate of 20℃ / min ensures its elution within an appropriate retention time, avoiding overlap with other impurities.

[0123] A final temperature of 250℃ is high enough to ensure complete separation of DMCC and its related impurities without residual interference.

[0124] The above is a detailed description of the invention, and the following is an example of the invention.

[0125] Example 1

[0126] Determine the concentration of dimethylcarbamoyl chloride by gas chromatography-mass spectrometry. The detailed operation steps are as follows:

[0127] S1 Set up the chromatographic column.

[0128] The chromatographic column is set to DB-624, with specifications of 30 m x 0.32 mm, 1.8 μm; and the gas chromatography-mass spectrometry (GC-MS) is confirmed to be correctly installed and debugged.

[0129] S2 Select the carrier gas and adjust its purity and flow rate, with a flow rate of 1.5 ml / min

[0130] The carrier gas is nitrogen, and its purity and flow rate are ensured to meet the requirements.

[0131] S3 Configure solutions: configure the DMCC control solution, test sample solution, and system suitability solution.

[0132] DMCC control solution (0.3 μg / ml): accurately weigh 30 mg of DMCC into a 10 ml volumetric flask, add an appropriate amount of diluent dichloromethane to make up to 10 ml, and shake well; transfer 1 ml from the above solution to another 100 ml volumetric flask, and again use the diluent to make up to 100 ml, shake well; repeat this step once to obtain a final concentration of 0.3 μg / ml of the DMCC control solution.

[0133] Test sample solution (100 mg / ml): accurately weigh 1 g of test sample into a 10 ml volumetric flask, add diluent to make up to volume, and shake well.

[0134] System suitability solution: after adding 1 g of test sample to a 10 ml volumetric flask, use the DMCC control solution to make up to volume, and shake well.

[0135] S4 Start the GC-MS system:

[0136] Turn on the instrument power, preheat the equipment to the specified temperature according to the manufacturer's operation manual, and tune the gas chromatography instrument performance (ISQ Dashboard).

[0137] Set the temperature program: initial temperature 80℃ for 2 minutes, then increase to 250℃ at a rate of 20℃ / min, and maintain at this temperature for 6 minutes; total running time is 16.5 minutes.

[0138] Set the acquisition molecular weight to 107, select electron ionization (EI) as the ion source type, and set the injection port temperature, ion source temperature, and ion transmission line temperature to 250℃; the split ratio is set to 50:1.

[0139] S5 Sample injection:

[0140] Using a microsyringe to suck 1 μl of sample solution or control solution, avoid using plastic dropper to prevent pollution; Carefully inject the sample into the GC injection port, get the data after analysis.

[0141] Data analysis:

[0142] Collect data and generate chromatogram and mass spectrum.

[0143] Compare the response of the blank solvent peak and the target compound (DMCC) to confirm that there is no interference. Collect data and generate chromatogram and mass spectrum, get the blank solvent peak chromatogram of Figure 1 and the chromatogram of the target compound (DMCC) of Figure 2 .

[0144] Figure 2 Blank solvent peak chromatogram, Figure 3 Chromatogram of target compound (DMCC)

[0145] Results record and report

[0146] The following data is the accuracy data, the purpose of accuracy verification is to confirm the closeness between the determination results of the existing method for the measured object within a certain range and the true value or reference value, generally expressed by recovery. The following data is 6 times of DMCC standard addition of the same concentration for one test sample, calculate the recovery

[0147] Table 1 Recovery calculation table

[0148]

[0149]

[0150] Results:

[0151] The recovery rate of 6 portions of 100% limit standard addition DMCC should be 70.0% ~ 130.0%, RSD ≤ 20%.

[0152] Table 2 limit of quantification data table

[0153]

[0154] Results:

[0155] (1) The signal-to-noise ratio of the limit of quantification peak of DMCC should be greater than 10;

[0156] (2) The peak area RSD of 6 consecutive limit of quantification concentrations should not be greater than 20%;

[0157] (3) Limit of quantification = 20.7 (S / N) = 0.000062 (mg / ml) = 20.61% (equivalent to limit concentration %).

[0158] Table 3 limit of detection data table

[0159]

[0160] Results:

[0161] (1) The signal-to-noise ratio of the 2-needle detection limit should be greater than 3;

[0162] (2) The detection limit = 4.75 (S / N) = 0.00012 (mg / ml) = 4.123% (equivalent to limit concentration %).

[0163] Table 4 durability data table

[0164]

[0165] Results:

[0166] (1) The blank solution has no interference with the relevant chromatographic peaks, and the sample solution has no interference with the relevant chromatographic peaks;

[0167] (2) The RSD of the peak area of the main component under the continuous 3-needle parameter investigation items should be ≤20%.

[0168] Table 5 linear data table

[0169] Concentration pg / ml Peak area LOQ 0.0619 390.437 50% STD 0.1549 889.130 100% STD 0.3097 1467.084 120% STD 0.3716 1766.716 150% STD 0.4646 2254.866

[0170] According to Table 5, the concentration and peak area linear graph of DMCC detection is obtained, and the results are: Figure 3

[0171] (1) The correlation coefficient R 2 ≥0.99.

[0172] (2) The intercept of the y-axis is 1.93%, which is not greater than 10%.

[0173] The blank solvent peak and 3-(N,N-dimethylaminocarbonyloxy) pyridine do not interfere with the detection of DMCC, and the linear relationship of DMCC is good within the range of 0.062 μg / ml-0.464 μg / ml (r=0.9919), the average recovery rate is 109.36% (RSD=10.3%), and the detection limit and the limit of quantification are 0.024 μg / ml and 0.062 μg / ml, respectively. The method has good durability.

[0174] Example 2

[0175] Using toluene as a diluent, the operation process is consistent with Example 1, and the typical chromatogram is obtained after detection Figure 4 ​The control solution: precisely pipette 30 mg of DMCC control into a 10 ml volumetric flask, dilute to the mark with toluene; precisely pipette 1.0 ml into a 100 ml volumetric flask, dilute to the mark with toluene; precisely pipette 1.0 ml into a 100 ml volumetric flask, dilute to the mark with toluene. The system suitability solution: take about 1 g of the sample, accurately weigh, put into a 10 ml volumetric flask, dilute to the mark with the control solution.

[0176] Example 3

[0177] Using acetonitrile as diluent, the operation process is consistent with that of Example 1, and a typical chromatogram is obtained after detection Figure 5 The control solution: precisely pipette 30 mg of DMCC control into a 10 ml volumetric flask, dilute to the mark with toluene; precisely pipette 1.0 ml into a 100 ml volumetric flask, dilute to the mark with toluene; precisely pipette 1.0 ml into a 100 ml volumetric flask, dilute to the mark with toluene. The system suitability solution: take about 1 g of the sample, accurately weigh, put into a 10 ml volumetric flask, dilute to the mark with the control solution.

[0178] From Figure 4 and Figure 5 It can be known that toluene and acetonitrile as diluent can detect DMCC, and the blank does not interfere with the detection of the sample, and the sample does not interfere with the detection of DMCC.

[0179] The above is only the preferred embodiment of the present application, it should be noted that the above preferred embodiment should not be regarded as limiting the present application, the protection scope of the present application should be limited by the scope defined by the claims. For ordinary skilled in the art, without departing from the spirit and scope of the present application, a number of improvements and refinements can also be made, which improvements and refinements should also be regarded as the protection scope of the present application.

Claims

1. A gas chromatography-mass spectrometry method for the analysis of dimethylcarbamoyl chloride, characterized in that: Includes the following steps: S1 is used to set the chromatographic column; S2 is the carrier gas; its purity and flow rate are adjusted. S3 Preparation Solutions: Prepare DMCC control solution, test solution, and system suitability solution; S4 starts the GC-MS system: Set the heating program: Initial temperature 60-80℃, hold for 2 minutes, then increase the temperature to 250℃ at a rate of 15-20℃ / min, and hold at this temperature for 6-10 minutes; Set the molecular weight to be collected to 107, select electron ionization (EI) as the ion source type, and set the injection port temperature, ion source temperature and ion transport line temperature. S5 sample injection: Use a microsyringe to draw up the sample solution or control solution; carefully inject the sample into the GC inlet, and obtain the data after analysis.

2. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 1, characterized in that: In step S1, the chromatographic column is a DB-624 with dimensions of 30m × 0.32mm and 1.8μm.

3. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 1, characterized in that: In step S2, the carrier gas is nitrogen.

4. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 1, characterized in that: In step S3, the concentration of the DMCC control solution is 0.3 μg / ml.

5. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 1, characterized in that: In step S3, the concentration of the test solution is 100 mg / ml.

6. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 1, characterized in that: In step S4, the injection port temperature, ion source temperature, and ion transport line temperature are all 250°C.

7. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 1, characterized in that: In step S4, the split ratio is set to 50:

1.

8. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 4, characterized in that: The preparation method of the DMCC control solution in step S3 is as follows: accurately weigh 30 mg of DMCC into a 10 ml volumetric flask, add an appropriate amount of diluent to bring the volume to 10 ml, and shake well; transfer 1 ml of the above solution to another 100 ml volumetric flask, and again dilute to 100 ml with diluent, and shake well; repeat this step once to obtain a DMCC control solution with a final concentration of 0.3 μg / ml.

9. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 8, characterized in that: The diluent is one of dichloromethane, toluene, or acetonitrile.

10. The gas chromatography-mass spectrometry analysis method for dimethylcarbamoyl chloride according to claim 5, characterized in that: The method for preparing the test solution is as follows: accurately weigh 1g of the test sample, place it in a 10ml volumetric flask, add diluent to make up to 10ml, and shake well.

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