Method for detecting trace dimethylamine in methylamine solution

Abstract

The invention provides a method for detecting trace dimethylamine in a methylamine solution, which comprises the following steps: (1) mixing a derivatization reagent with alkali and a solvent to obtain a derivatization reagent solution; (2) mixing a reference substance with the derivatization reagent solution to obtain a reference substance solution; (3) mixing a to-be-detected sample with the derivatization reagent solution for reaction to obtain a test solution; and (4) respectively carrying out gas chromatography detection on the test solution and the reference solution, and calculating the content of dimethylamine in the sample to be detected according to the detection result. The method provided by the invention can effectively separate the dimethylamine component in methylamine, realizes effective detection of trace dimethylamine in the methylamine solution, and has the advantages of high specificity, high sensitivity, high precision, high accuracy, wide linear range and good durability.

Description

Technical Field

[0001] The present invention belongs to the technical field of analytical chemistry, and particularly relates to a method for detecting trace dimethylamine in methylamine ethanol solution. Background Art

[0002] Methylamine is a medium-strong alkaline, colorless and flammable gas at room temperature. Commercially available methylamine is commonly in the form of ethanol, tetrahydrofuran or aqueous solution. It is one of the important basic fine chemical raw materials and is widely used in fields such as pesticides, pharmaceuticals, rubber, leather making, synthetic dyes, synthetic resins, chemical fibers, surfactants, explosives and feed additives. Among them, the consumption in pesticide production accounts for 60%, the consumption in pharmaceutical production accounts for 15%, the consumption in dyes accounts for 10%, and the consumption in other fields accounts for 5%. At present, in the pharmaceutical industry, it has been widely used in the synthesis of drugs such as meglumine and fosaprepitant dimeglumine.

[0003] Impurities in drugs refer to substances that have no therapeutic effect or affect the stability, efficacy, and even are harmful to human health in drugs. In aspects such as drug research, production, storage, and clinical application, it is necessary to ensure the purity of drugs and reduce drug impurities to ensure the effectiveness and safety of drugs. As a commonly used raw material for drug synthesis, trace amounts of dimethylamine are inevitably produced in the current production process of preparing methylamine solution. Both dimethylamine and methylamine are lower aliphatic amines with very similar properties, and by-products substituted with dimethylamine will inevitably be produced in the synthesis process. Therefore, reducing the residual dimethylamine in methylamine and ensuring the quality of methylamine play a very important role in impurity control, process optimization research, and ensuring the quality and safety of raw materials.

[0004] At present, common methods for detecting methylamine and dimethylamine include spectrophotometry, gas chromatography, liquid chromatography, ion chromatography, etc. Spectrophotometry generally uses reagents to derivatize methylamine and dimethylamine to generate substances with ultraviolet absorption, but this method has low sensitivity, low efficiency and poor repeatability. Gas chromatography is currently the main method for detecting short-chain fatty amines. However, at room temperature, both methylamine and dimethylamine are low-boiling and volatile gases, with weak retention on the gas chromatography column, difficult separation, and it is difficult to pass the recovery rate. Liquid chromatography is a classic method for measuring the content of lower aliphatic amines. Since these compounds have large polarity and low response values to liquid chromatography detectors, no chromophore, no fluorescence characteristics and no ultraviolet absorption characteristics, they often need to be derivatized first to achieve easy separation and detection. However, the derivatives of methylamine and dimethylamine have similar properties and are difficult to separate in the liquid phase and have a high detection limit. Ion chromatography has high analysis efficiency and good method sensitivity, but some common cations will seriously affect the detection results. For raw materials with strict impurity control, there is an urgent need for a method to accurately detect trace levels of dimethylamine in order to better control the safety of drugs. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a method for detecting trace dimethylamine in methylamine ethanol solution. The method provided by the present invention can effectively separate the dimethylamine component in methylamine, realizing the effective detection of trace dimethylamine in methylamine solution, and has the advantages of high specificity, high sensitivity, high precision, high accuracy, good linear range and durability.

[0006] To achieve the purpose of this invention, the following technical solutions are adopted:

[0007] The present invention provides a method for detecting trace dimethylamine in methylamine solution, and the detection method includes the following steps:

[0008] (1) Mix a derivatizing reagent with a base and a solvent to obtain a derivatizing reagent solution;

[0009] (2) Mix a reference substance with the derivatizing reagent solution to obtain a reference substance solution;

[0010] (3) Mix a sample to be tested with the derivatizing reagent solution for reaction to obtain a test sample solution;

[0011] (4) Perform gas chromatography - mass spectrometry detection on the test sample solution and the reference substance solution respectively, and calculate the content of dimethylamine in the sample to be tested according to the detection results.

[0012] Steps (2) and (3) do not distinguish the order.

[0013] The concentration of dimethylamine in the sample to be tested is not higher than 0.3 μg / mL.

[0014] The above method conducts a derivatization reaction through a derivatizing reagent to add a chromogenic group to amines with low boiling points and weak ultraviolet absorption. At the same time, the derivatized amines with low boiling points can also have higher melting and boiling points, facilitating separation; in addition, an alkali solution is used as an acid - binding agent, which can improve the reaction yield, reduce the occurrence of side reactions, and improve the accuracy of detection; at the same time, this detection method uses a mass spectrometry detector with high sensitivity, and finally makes the detection method have the advantages of high specificity, high sensitivity, high precision, high accuracy, wide linear range and good solution stability.

[0015] Preferably, the derivatizing reagent in step (1) is p - toluenesulfonyl chloride.

[0016] Preferably, the solvent in step (1) is dichloromethane.

[0017] Preferably, the base in step (1) includes any one or a combination of at least two of pyridine, ammonia water or triethylamine (TEA), and triethylamine is preferred.

[0018] Preferably, the mass ratio of the derivatization reagent to the base in step (1) is (3 - 5):(3 - 5), such as 3:5, 3.5:4.5, 4:4, 4.5:3.5, or 5:3, etc., but not limited to the values listed above. Other unlisted values within the above numerical range are equally applicable.

[0019] Preferably, the mass ratio of the derivatization reagent to the sample to be tested in step (3) is (15 - 25):3, such as 15:3, 16:3, 17:3, 18:3, 19:3, 20:3, 21:3, 22:3, 23:3, 24:3, or 25:3, etc., but not limited to the values listed above. Other unlisted values within the above numerical range are equally applicable.

[0020] Preferably, the chromatographic column for the gas chromatography - mass spectrometry detection in step (4) is HP - 5ms Ultra Inert, 30m×0.25mm, 0.25μm.

[0021] Preferably, in the gas chromatography - mass spectrometry detection in step (4), the inlet temperature is 240 - 260°C, the detector temperature is 240 - 260°C, and the transfer line temperature is 260 - 280°C.

[0022] Among them, the inlet temperature can be 240°C, 245°C, 250°C, 255°C, or 260°C, etc., the detector temperature can be 240°C, 245°C, 250°C, 255°C, or 260°C, etc., and the transfer line temperature can be 260°C, 265°C, 270°C, 275°C, or 280°C, etc., but not limited to the values listed above. Other unlisted values within the above numerical range are equally applicable.

[0023] Preferably, in the gas chromatography - mass spectrometry detection in step (4), a PSD switching valve is used to switch the signal peak of the sample to be tested between the gas phase detector and the mass spectrometry detector (which can block the contamination of the mass spectrometry detector by larger impurity peaks); or a two - way connection is used to connect the gas chromatography column and the mass spectrometry detector (all signals enter the mass spectrometry detector).

[0024] Preferably, in the gas chromatography - mass spectrometry detection in step (4), the flow rate of the carrier gas is 1 - 1.5 mL / min, such as 1 mL / min, 1.1 mL / min, 1.2 mL / min, 1.3 mL / min, 1.4 mL / min, 1.5 mL / min, etc., but not limited to the values listed above. Other unlisted values within the above numerical range are equally applicable.

[0025] Preferably, in the gas chromatography - mass spectrometry detection in step (4), the temperature - rising program is as follows:

[0026] Starting from a temperature of 70 - 90 °C, heating to 290 - 310 °C at a heating rate of 19 - 21 °C / min, and maintaining for 10 min.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The present invention provides a method for detecting trace dimethylamine in methylamine solution. Through a derivatization reagent for derivatization reaction, chromogenic groups are added to amines with low boiling points and weak ultraviolet absorption. At the same time, the derivatized amines with low boiling points can also have higher melting and boiling points, facilitating separation; in addition, using an alkali solution as an acid-binding agent can improve the reaction yield, reduce the occurrence of side reactions, and improve the accuracy of detection; at the same time, this detection method uses a mass spectrometry detector with high sensitivity, and finally makes the detection method have the advantages of high specificity, high sensitivity, high precision, high accuracy, wide linear range, and good solution stability. Description of the Drawings

[0029] Figure 1 The spectrogram obtained from the detection of Example 1;

[0030] Figure 2 The spectrogram obtained from the detection of Example 2;

[0031] Figure 3 The spectrogram obtained from the detection of Example 3;

[0032] Figure 4 The spectrogram obtained from the detection of Example 9;

[0033] Figure 5 The spectrogram obtained from the detection of Example 10;

[0034] Figure 6 The spectrogram obtained from the detection of Example 11;

[0035] Figure 7 The spectrogram obtained from the detection of Example 12;

[0036] Figure 8 The spectrogram obtained from the detection of Example 13;

[0037] Figure 9 The spectrogram obtained from the detection of Example 14;

[0038] Figure 10 The spectrogram obtained from the detection of Example 15;

[0039] Figure 11 The spectrogram obtained from the detection of Example 16;

[0040] Figure 12 The spectrogram obtained from the detection of Example 17. Detailed Embodiments

[0041] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0042] The reagents and instruments used in the following examples are as follows:

[0043] Gas chromatography: Model: Agilent 8890-5977B, Agilent Technologies Ltd.;

[0044] Detector: mass spectrometer EI detector, Agilent Technologies Ltd.;

[0045] Chromatographic column: HP-5ms Ultra Inert (30m×0.25m, 0.25μM), Agilent Technologies Ltd.

[0046] Analytical balance: XPR205DU, Mettler GmbH;

[0047] N,N-Dimethyl-p-toluenesulfonamide: analytical grade, Nanjing Yaoshi Technology Co., Ltd.;

[0048] p-Toluenesulfonyl chloride: analytical grade, Maclean Co., Ltd.;

[0049] Dichloromethane: HPLC grade, Adamas Reagent Co., Ltd.;

[0050] Triethylamine (TEA): analytical grade, Zhejiang Jianye Co., Ltd.;

[0051] Ammonia: HPLC grade, Aladdin Co., Ltd.

[0052] Pyridine: analytical grade, Nanjing Reagent Co., Ltd.;

[0053] Test sample: Methylamine ethanol solution, Nanjing Yaoshi Technology Co., Ltd.

[0054] Preparation Example 1

[0055] This preparation example provides a reference solution, and its preparation method is as follows:

[0056] Accurately weigh 10 g of p-toluenesulfonyl chloride and 10 g of triethylamine, dissolve them in 500 mL of dichloromethane, and mix them evenly to obtain a diluent.

[0057] Accurately weigh 120 mg of N,N-dimethyl-p-toluenesulfonamide, dissolve it in 25 mL of diluent, mix well to obtain N,N-dimethyl-p-toluenesulfonamide stock solution 1. Measure 1 mL of N,N-dimethyl-p-toluenesulfonamide stock solution 1, add diluent, make up the volume to 20 mL in a volumetric flask, and mix well to obtain N,N-dimethyl-p-toluenesulfonamide stock solution 2. Measure 1 mL of N,N-dimethyl-p-toluenesulfonamide stock solution 2, add diluent, make up the volume to 20 mL in a volumetric flask, and mix well to obtain N,N-dimethyl-p-toluenesulfonamide stock solution 3. Measure 2 mL of N,N-dimethyl-p-toluenesulfonamide stock solution 3, add diluent, make up the volume to 20 mL in a volumetric flask, and mix well to obtain the reference solution.

[0058] Preparation Example 2

[0059] This preparation example provides a test solution, and its preparation method is as follows:

[0060] Accurately weigh 600 mg of the sample to be tested, dissolve it in 10 mL of dichloromethane, mix well to obtain the sample stock solution. Measure 1 mL of the sample stock solution, add the diluent in Preparation Example 1, make up the volume to 20 mL in a volumetric flask, and mix well to obtain the test solution.

[0061] Preparation Example 3

[0062] This preparation example provides a sensitivity solution, and its preparation method is as follows:

[0063] Measure 5 mL of the reference solution in Preparation Example 1, add the diluent in Preparation Example 1, make up the volume to 20 mL in a volumetric flask, and mix well to obtain the sensitivity solution.

[0064] Preparation Example 4

[0065] This preparation example provides a linear solution, and its preparation method is as follows:

[0066] Respectively measure 0.5, 1, 2, 3, 4 mL of N,N-dimethyl-p-toluenesulfonamide stock solution 3 in Preparation Example 1, add the diluent in Preparation Example 1, and respectively make up the volume to 20 mL in a volumetric flask, and mix well to obtain linear solutions of 25% (LOQ), 50%, 100%, 150%, and 200%.

[0067] Preparation Example 5

[0068] This preparation example provides a spiked solution, and its preparation method is as follows:

[0069] Respectively measure 0.5, 2, 3 mL of N,N-dimethyl-p-toluenesulfonamide stock solution 3 in Preparation Example 1, respectively mix them with 1 mL of the sample stock solution in Preparation Example 2, add the diluent in Preparation Example 1, and make up the volume to 20 mL to obtain spiked solutions of 25%, 100%, and 150%.

[0070] Preparation Example 6

[0071] This preparation example provides a test solution. In the specific steps, except that triethylamine in the diluent in Preparation Example 1 is replaced by pyridine, the rest is the same as Preparation Example 1.

[0072] Preparation Example 7

[0073] This preparation example provides a test solution. In the specific steps, except that triethylamine in the diluent in Preparation Example 1 is replaced by ammonia water, the rest is the same as Preparation Example 1.

[0074] Preparation Example 8

[0075] This preparation example provides a test solution. In the specific steps, except that 10 g of p-toluenesulfonyl chloride in the diluent in Preparation Example 1 is replaced by 7.5 g of p-toluenesulfonyl chloride, the rest is the same as Preparation Example 1.

[0076] Preparation Example 9

[0077] This preparation example provides a test solution. In the specific steps, except that 10 g of p-toluenesulfonyl chloride in the diluent in Preparation Example 1 is replaced by 12.5 g of p-toluenesulfonyl chloride, the rest is the same as Preparation Example 1.

[0078] Preparation Example 10

[0079] This preparation example provides a test solution. In the specific steps, except that 10 g of triethylamine in the diluent in Preparation Example 1 is replaced by 7.5 g of triethylamine, the rest is the same as Preparation Example 1.

[0080] Preparation Example 11

[0081] This preparation example provides a test solution. In the specific steps, except that 10 g of triethylamine in the diluent in Preparation Example 1 is replaced by 12.5 g of triethylamine, the rest is the same as Preparation Example 1.

[0082] Example 1

[0083] This example provides a method for detecting trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0084] Inject the reference solution and diluent obtained in Preparation Example 1 into the gas chromatograph - mass spectrometer respectively. The injection volume is 1 μL. Use an HP - 5ms Ultra Inert (30 m×0.25 m, 0.25 μM) chromatographic column. The carrier gas is helium. Use a PSD switching valve. The quartz column connected to the mass spectrometry part is 2.23 m×0.15 mm, and the quartz column connected to the gas chromatography part is 0.3 m×0.10 mm. The carrier gas flow rate leading to the PSD switching valve is 1.4 mL / min, and the carrier gas flow rate leading to the gas chromatography is 2.8 mL / min. The split ratio is 10:1. The injection port temperature is 250 °C, the detector temperature is 250 °C, the transfer line temperature is 270 °C, the ion source temperature is 230 °C, the quadrupole temperature is 150 °C. The ion source is an EI source, and the ion source energy is 70 eV. The molecular ion peak is 199.0. The column temperature is maintained at 80 °C for 0 min as the starting temperature, and then heated to 300 °C at a rate of 20 °C / min and held for 10 min. The results show that the diluent has no interference, and the detected results are as shown in Table 1 and Figure 1 (The abscissa is time and the ordinate is intensity, the same hereinafter), indicating that the detection method provided by the present invention has strong specificity for detecting trace dimethylamine in methylamine ethanol solution.

[0085] Table 1

[0086]

[0087]

[0088] Example 2

[0089] This example provides a detection method for detecting trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0090] The difference from Example 1 is only that the reference solution obtained in Preparation Example 1 is replaced with the test solution obtained in Preparation Example 2 and injected into the gas chromatograph - mass spectrometer. The injection volume and detection method parameters are the same as those in Example 1. The detected characteristic chromatogram is as Figure 2 shown. It can be seen from the figure that the retention time of the characteristic peak of N,N - dimethyl - p - toluenesulfonamide is 7.7 min.

[0091] Example 3

[0092] This example provides a detection method for detecting trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0093] The difference from Example 1 is only that the reference solution obtained in Preparation Example 1 is replaced with the sensitivity solution obtained in Preparation Example 3. Prepare 3 parallel portions and perform gas chromatograph - mass spectrometry detection on them. The injection volume and detection method parameters are the same as those in Example 1. The detected characteristic chromatogram is as Figure 3As shown; the test results are shown in Table 2:

[0094] Table 2

[0095]

[0096]

[0097] According to the table data, the quantitative limit of this detection method is 100 ppm, indicating that the method for detecting trace dimethylamine in methylamine ethanol solution provided by the present invention has good sensitivity.

[0098] Example 4

[0099] This example provides a detection method for detecting trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0100] The difference from Example 1 is only that the reference solution obtained in Preparation Example 1 is continuously injected six times for gas chromatography detection, and the injection volume and detection method parameters are the same as those in Example 1. The test results are shown in Table 3:

[0101] Table 3

[0102]

[0103] According to the table data, after continuously injecting and testing 6 times, the relative standard deviation RSD% of the retention time is 1.4, and the RSD% of the peak area is 0.03%, indicating that the method for detecting trace dimethylamine in methylamine ethanol solution provided by the present invention has good system precision.

[0104] Example 5

[0105] This example provides a detection method for detecting trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0106] The difference from Example 1 is only that six parallel samples of the reference solution obtained in Preparation Example 1 are separately subjected to gas chromatography detection, and the injection volume and detection method parameters are the same as those in Example 1. The test results are shown in Table 4:

[0107] Table 4

[0108]

[0109] According to the table data, after parallel testing 6 times, the relative standard deviation RSD% of the recovery rate is 1.6, indicating that the method for detecting trace dimethylamine in methylamine ethanol solution provided by the present invention has good repeatability.

[0110] Example 6

[0111] This embodiment provides a detection method for trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0112] The difference from Example 1 is only that the reference solution obtained in Preparation Example 1 is replaced with the linear solution obtained in Preparation Example 4, and they are respectively injected into the gas chromatograph. The injection volume and the detection method parameters are the same as those in Example 1. The detection results are shown in Table 5:

[0113] Table 5

[0114]

[0115] Example 7

[0116] This embodiment provides a detection method for trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0117] The difference from Example 1 is only that the reference solution obtained in Preparation Example 1 is subjected to gas chromatography-mass spectrometry (GC-MS) detection at 0 h, 6.7 h, 8.9 h, 11.0 h, and 13.1 h respectively. The injection volume and the detection method parameters are the same as those in Example 1. The detection results are shown in Table 6:

[0118] Table 6

[0119]

[0120] According to the data in the table, it can be seen that the detection method has good stability within 13.1 h, indicating that the detection method for trace dimethylamine in methylamine ethanol solution by gas chromatography-mass spectrometry provided by the present invention has good stability.

[0121] Example 8

[0122] This embodiment provides a detection method for trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0123] The difference from Example 1 is only that the reference solution obtained in Preparation Example 1 is replaced with the spiked solution obtained in Preparation Example 5, and gas chromatography-mass spectrometry detection is carried out. The injection volume and the detection method parameters are the same as those in Example 1. Each concentration is tested in parallel three times, and the detection results are shown in Table 7:

[0124] Table 7

[0125]

[0126]

[0127] According to the data in the table, it can be seen that the recovery rate of this detection method is between 105-115%, indicating that the detection method for trace dimethylamine in methylamine ethanol solution by gas chromatography-mass spectrometry provided by the present invention has good accuracy and recovery rate.

[0128] Example 9

[0129] This example provides a detection method for trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0130] The difference from Example 1 is only that in the detection method parameters, the PSD switching valve is not connected, and a double-pass is directly used to connect the gas chromatography column and the mass spectrometry part together. The carrier gas flow rate is set to 1.4 mL / min, and other parameters are the same as those in Example 1. The specific results are as Figure 4 shown.

[0131] Example 10

[0132] This example provides a detection method for trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0133] The difference from Example 9 is only that according to Preparation Example 6, the triethylamine in the diluent in Preparation Example 1 is replaced with an equal amount of pyridine for gas chromatography-mass spectrometry detection. The injection volume and detection method parameters are the same as those in Example 9. Pyridine has a weak acid-binding ability as an acid-binding agent, and the solution becomes turbid after derivation, so it cannot be used to detect trace dimethylamine in methylamine ethanol solution. The results are as Figure 5 shown.

[0134] Example 11

[0135] This example provides a detection method for trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0136] The difference from Example 9 is only that according to Preparation Example 7, the triethylamine in the diluent in Preparation Example 1 is replaced with an equal amount of ammonia water (20 mg / mL) for gas chromatography-mass spectrometry detection. The injection volume and detection method parameters are the same as those in Example 9. Ammonia water has a weak acid-binding ability as an acid-binding agent, and the solution becomes turbid after derivation, so it cannot be used to detect trace dimethylamine in methylamine ethanol solution. The results are as Figure 6 shown.

[0137] Example 12

[0138] This example provides a detection method for trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0139] The difference from Example 9 is only that the reference solution obtained in Preparation Example 1 is replaced with Preparation Examples 8-11 for gas chromatography-mass spectrometry detection. The sample injection volume and detection method parameters are the same as those in Example 9. When the mass ratio of the derivatizing reagent to the alkali solution is (3-5):(3-5) or the mass ratio of the derivatizing reagent to the sample to be detected is (15-25):3, the influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide is relatively small, and the results are as Figure 7 shown.

[0140] Example 13

[0141] This example provides a method for detecting trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0142] The difference from Example 9 is only that the carrier gas flow rate is adjusted to 1.0 mL / min, 1.2 mL / min, 1.3 mL / min, 1.4 mL / min or 1.5 mL / min, and the rest is the same as that in Example 9. When the carrier gas flow rate is adjusted to 1.0 mL / min, 1.2 mL / min, 1.3 mL / min, 1.4 mL / min or 1.5 mL / min, the influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide is relatively small, and the results are as Figure 8 shown.

[0143] Example 14

[0144] This example provides a method for detecting trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0145] The difference from Example 9 is only that the initial temperature of the programmed temperature rise is set to 70 °C or 90 °C, and the rest is the same as that in Example 9. When the initial temperature of the programmed temperature rise is set to 70 °C or 90 °C, the influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide is relatively small, and the results are as Figure 9 shown.

[0146] Example 15

[0147] This example provides a method for detecting trace dimethylamine in methylamine ethanol solution. The detection method is as follows:

[0148] The difference from Example 9 is only that the final temperature of the programmed temperature rise is set to 290 °C or 310 °C, and the rest is the same as that in Example 9. When the final temperature of the programmed temperature rise is set to 290 °C or 310 °C, the influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide is relatively small, and the results are as Figure 10 shown.

[0149] Example 16

[0150] This embodiment provides a method for detecting trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0151] The difference from Example 9 is only that, except that the inlet temperature is 240, 260 °C, the detector temperature is 240, 260 °C, and the transfer line temperature is 260, 280 °C, the rest is the same as Example 9. The inlet temperature of 240, 260 °C, the detector temperature of 240, 260 °C, and the transfer line temperature of 260, 280 °C have little influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide. The results are as Figure 11 shown.

[0152] Example 17

[0153] This embodiment provides a method for detecting trace dimethylamine in methylamine ethanol solution, and the detection method is as follows:

[0154] The difference from Example 9 is only that, except that the programmed temperature increase rate is set to 15 °C / min, 19 °C / min, 21 °C / min or 25 °C / min, the rest is the same as Example 9. Among them, setting the programmed temperature increase rate to 19 °C / min or 21 °C / min has little influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide; setting the programmed temperature increase rate to 15 °C / min has a certain influence on the peak emergence and resolution of N,N-dimethyl-p-toluenesulfonamide, and the resolution is only 1.86, and there are large interfering substances not far from the peak emergence of the target substance, which may interfere with the peak emergence of N,N-dimethyl-p-toluenesulfonamide; while setting the programmed temperature increase rate to 25 °C / min, the resolution does not meet the system suitability requirement of being greater than 1.5 (1.36). The results are as Figure 12 shown.

[0155] The applicant declares that the present invention uses the above embodiments to illustrate the detection method of trace dimethylamine in the methylamine solution of the present invention, but the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, the equivalent replacement of each raw material of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc. all fall within the protection scope and disclosure scope of the present invention.

[0156] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept scope of the present invention, various simple modifications can be made to the technical solutions of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0157] In addition, it should be noted that, in the above specific embodiments, the various specific technical features described can be combined in any appropriate manner without contradiction. To avoid unnecessary repetition, the present invention will not separately describe various possible combinations.

Claims

1. A method for detecting trace dimethylamine in methylamine solution, characterized in that, The detection method includes the following steps: (1) Mix the derivatization reagent with a base and a solvent to obtain a derivatization reagent solution; (2) Mix the reference substance with the derivatization reagent solution to obtain a reference substance solution; (3) Mix the sample to be tested with the derivatization reagent solution for reaction to obtain a test sample solution; (4) Perform gas chromatography - mass spectrometry (GC - MS) detection on the test sample solution and the reference substance solution respectively, and calculate the content of dimethylamine in the sample to be tested according to the detection results; Steps (2) and (3) do not distinguish the order; The concentration of dimethylamine in the sample to be tested is not higher than 0.3 μg / mL.

2. The detection method according to claim 1, wherein The derivatization reagent in step (1) is p - toluenesulfonyl chloride.

3. The detection method according to claim 1 or 2, characterized in that, The solvent in step (1) is dichloromethane.

4. The detection method according to any one of claims 1-3, characterized in that, The base in step (1) includes any one or a combination of at least two of pyridine, ammonia water or triethylamine, preferably triethylamine.

5. The detection method according to any one of claims 1-4, characterized in that, The mass ratio of the derivatization reagent to the base in step (1) is (3 - 5):(3 - 5).

6. The detection method according to any one of claims 1-5, characterized in that, The mass ratio of the derivatization reagent to the sample to be tested in step (3) is (15 - 25):

3.

7. The detection method according to any one of claims 1-6, characterized in that, The chromatographic column for the GC - MS detection in step (4) is HP - 5ms Ultra Inert, 30 m×0.25 mm, 0.25 μm.

8. The detection method according to any one of claims 1-7, characterized in that, In the GC - MS detection in step (4), the inlet temperature is 240 - 260 °C, the detector temperature is 240 - 260 °C, and the transfer line temperature is 260 - 280 °C.

9. The detection method according to any one of claims 1-8, characterized in that, In the GC - MS detection in step (4), use a PSD switching valve to switch the signal peak of the sample to be tested between the gas chromatograph detector and the mass spectrometer detector; or use a two - way connection between the gas chromatographic column and the mass spectrometer detector; Preferably, in the GC - MS detection in step (4), the flow rate of the carrier gas is 1 - 1.5 mL / min.

10. The detection method according to any one of claims 1-9, characterized in that, In the GC - MS detection in step (4), the temperature - rising program is as follows: Start at a temperature of 70 - 90 °C, increase the temperature at a rate of 19 - 21 °C / min to 290 - 310 °C, and hold for 10 min.

Images