CN113009046B - GC-MS-MS detection and analysis method for synthesizing nicotine - Google Patents
GC-MS-MS detection and analysis method for synthesizing nicotine Download PDFInfo
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- CN113009046B CN113009046B CN202110341578.3A CN202110341578A CN113009046B CN 113009046 B CN113009046 B CN 113009046B CN 202110341578 A CN202110341578 A CN 202110341578A CN 113009046 B CN113009046 B CN 113009046B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/72—Mass spectrometers
Abstract
A GC-MS detection assay method for synthesizing nicotine, comprising the steps of: step one: taking a certain amount of nicotine prepared by the synthesis method, adding a solvent for dilution, and carrying out ultrasonic vibration for 3-5min to obtain a sample working solution, wherein the mass ratio of a nicotine sample to the solvent is 1:3-8; step two: and (3) injecting a sample working solution into a gas chromatography-mass spectrometer, and qualitatively analyzing all impurities in the synthesized nicotine by using the obtained spectrum through parameters of retention time, fragment peak shape and molecular weight. The detection method is simple, has accurate results, and is suitable for analyzing impurity components of the synthesized nicotine; the method effectively separates and determines the structure of main impurities in the synthesized nicotine by using a gas chromatography and mass spectrometry combined method, fills up the blank in the field, and is beneficial to popularization and development of the synthesized nicotine industry.
Description
Technical Field
The invention belongs to the field of detection of synthetic nicotine, and particularly relates to a GC-MS-MS detection and analysis method of synthetic nicotine.
Background
The nicotine is a liquid alkaloid, has strong physiological activity and has wide application in the fields of agriculture, medical intermediates and electronic cigarettes. The nicotine is obtained by plant extraction and artificial synthesis. The plant extraction method is mature in process, impurities mainly comprise known alkaloids such as pseudoscouring rush, ha Erjian, tobacco stand and the like, and a plurality of reports on impurity analysis are about the known alkaloids.
The synthesis method mainly comprises the steps of using ethyl nicotinate and N-vinyl pyrrolidone as raw materials, and obtaining nicotine through base catalysis of claisen condensation, acid decarboxylation ring closure, hydrogenation reduction, eschweiler-Clarke methylation, resolution and refining (the reaction formula is shown in figure 10). In recent years, synthetic production has been receiving attention because it is not limited by materials such as tobacco. However, at present, no detection method suitable for synthesizing nicotine is available, and the impurity components and structures are not clear.
Disclosure of Invention
The invention provides a GC-MS-MS detection analysis method for synthesizing nicotine, which is used for solving the defects in the prior art.
The invention is realized by the following technical scheme:
a GC-MS detection assay method for synthesizing nicotine, comprising the steps of:
step one: taking a certain amount of nicotine prepared by the synthesis method, adding a solvent for dilution, and carrying out ultrasonic vibration for 3-5min to obtain a sample working solution, wherein the mass ratio of a nicotine sample to the solvent is 1:3-8;
step two: injecting a sample working solution into a gas chromatography-mass spectrometer, wherein the gas chromatography conditions are as follows: the chromatographic column adopts a polyethylene glycol capillary column with the length of 30m, the inner diameter of the column is 0.18mm, the film thickness is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999 percent, the carrier gas flow rate is 1.0-1.5ml/min, the sample injection amount is 1 mu L, and the split ratio is 30-60:1; the mass spectrum conditions are as follows: EI ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode of full scanning, scanning range of 35-500amu, quadrupole temperature 160 ℃, transmission line temperature 270 ℃, solvent delay of 8min; the obtained map is used for carrying out qualitative analysis on each impurity in the synthesized nicotine through the parameters of retention time, fragment peak shape and molecular weight.
The GC-MS-MS detection and analysis method for synthesizing the nicotine comprises the step one, wherein the solvent is any one of ethanol, isopropanol and n-hexane.
The above-mentioned GC-MS-MS detection analysis method for synthesizing nicotine, wherein in the second step, the polyethylene glycol capillary is any one of a stabilwax polyethylene glycol capillary, a BP-20 polyethylene glycol capillary and a carbowax polyethylene glycol capillary.
The GC-MS-MS detection analysis method for the synthesized nicotine comprises the following steps of using a chromatographic column with an initial temperature of 60-100 ℃ for 2min, heating to 230-280 ℃ at 10 ℃/min, and maintaining for 2-6min.
According to the GC-MS-MS detection analysis method for synthesizing the nicotine, the first impurity in the map obtained in the third step is dichloromethane. By comparing the mass spectrum of the impurity with the mass spectrum database, the molecular weight of the impurity is 85, the molecular ion peak [ M+H ] + is 86, and the impurity is deduced to be methylene dichloride (the molecular formula of which is shown in FIG. 11), and the solvent residue is from the process route.
According to the GC-MS-MS detection and analysis method for synthesizing the nicotine, the impurity II in the map obtained in the step three is N-methyl pseudoscouring. By comparing the two mass spectra of the impurity with a mass spectrum database, the molecular weight of the ion peak M+ of the impurity is 176, and the molecular weight of the maximum fragment peak is 161, so that the impurity contains methyl, and by combining a nicotine synthesis process, the impurity is deduced to be N-methyl pseudoscouring (the molecular formula of which is shown in figure 12), and the five-membered heterocycle is rearranged and carburised to be six-membered heterocycle due to hypermethylation in the Eschweiler-Clarke reaction process.
According to the GC-MS-MS detection analysis method for synthesizing the nicotine, the impurity III in the map obtained in the step III is 2-isopropyl-4-hydroxy-1, 5 naphthyridine. By comparing the three mass spectrograms of the impurity with a mass spectrogram database, the molecular weight of the ion peak M+ of the impurity is 188, and the impurity is inferred to be 2-isopropyl-4-hydroxy-1, 5 naphthyridine (the molecular formula of the impurity is shown in figure 13).
According to the GC-MS-MS detection analysis method for synthesizing the nicotine, the impurity IV in the map obtained in the step three is myosmine. By comparing the mass spectrum of the impurity with the mass spectrum database, the molecular weight of the ion peak M+ of the impurity is 146, and the impurity is deduced to be Mastigmine (the molecular formula of which is shown in FIG. 14), and the residue of the two-step intermediate is obtained from the synthetic route.
The invention has the advantages that: the detection method is simple, has accurate results, and is suitable for analyzing impurity components of the synthesized nicotine; the method effectively separates and determines the structure of main impurities in the synthesized nicotine by using a gas chromatography and mass spectrometry combined method, fills up the blank in the field, and is beneficial to popularization and development of the synthesized nicotine industry.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions of the prior art, the drawings that are needed in the embodiments or the description of the prior art will be briefly described below, it will be obvious that the drawings in the following description are some embodiments of the present invention, and that other drawings can be obtained according to these drawings without inventive effort to a person skilled in the art.
FIG. 1 is a TIC chart of the total particle flow of synthesized nicotine according to the present invention, from which it is seen that there are four main impurities in the synthesized nicotine, except for nicotine: impurity one (5.8995 min), impurity two (20.5923 min), impurity three (22.1346 min), and impurity four (23.5893 min);
FIG. 2 is a mass spectrum of impurity one of example 1 of the present invention;
FIG. 3 is a mass spectrum of impurity II of example 1 of the present invention;
FIG. 4 is a mass spectrum of impurity three of example 1 of the present invention;
FIG. 5 is a mass spectrum of impurity four of example 1 of the present invention;
FIG. 6 is a mass spectrum of impurity one of example 2 of the present invention;
FIG. 7 is a mass spectrum of impurity II of example 2 of the present invention;
FIG. 8 is a mass spectrum of impurity III of example 2 of the present invention;
FIG. 9 is a mass spectrum of impurity four of example 2 of the present invention;
FIG. 10 is a reaction scheme for the prior art synthesis of nicotine;
FIG. 11 is a molecular formula of a first impurity determined by the detection of synthetic nicotine according to the present invention;
FIG. 12 is a molecular formula of a second impurity identified by the detection of synthetic nicotine according to the present invention;
FIG. 13 is a molecular formula of a third impurity identified by the detection of synthetic nicotine according to the present invention;
FIG. 14 is a molecular formula of a fourth impurity identified by the present invention for detecting synthetic nicotine.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
(1) Preparing a sample working solution: taking 0.5g of nicotine prepared by a synthesis method, adding 3.0g of n-hexane for dilution, and carrying out ultrasonic oscillation for 5min to obtain a sample working solution;
(2) Setting gas chromatography conditions: the chromatographic column adopts polyethylene glycol capillary column, the model is BP-20, the length is 30m, the inner diameter of the column is 0.18mm, the film thickness is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999%, the flow rate of the carrier gas is 1.0ml/min, the sample injection amount is 1 mu L, the split ratio is 40:1, and the chromatographic column adopts the following temperature programming: the initial temperature is 70 ℃, after the temperature is kept for 2 minutes, the temperature is increased to 260 ℃ at 10 ℃/min, and the temperature is kept for 4 minutes;
(3) Setting mass spectrum conditions: EI ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode of full scanning, scanning range of 35-500amu, quadrupole temperature 160 ℃, transmission line temperature 270 ℃, solvent delay of 8min;
(4) And (3) sample injection detection: and (3) injecting a sample working solution into a gas chromatograph-mass spectrometer, and effectively separating a nicotine main peak and four impurity peaks, wherein the main peak and the four impurity peaks are shown in figures 2-5.
Example 2
(1) Preparing a sample working solution: taking 0.5g of nicotine prepared by the synthesis method, adding 2.0g of ethanol for dilution, and carrying out ultrasonic vibration for 5min to obtain a sample working solution;
(2) Setting gas chromatography conditions: the chromatographic column adopts polyethylene glycol capillary column, the model is the stabilwax of the invention, the length is 30m, the inner diameter of the column is 0.18mm, the film thickness is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999%, the carrier gas flow rate is 1.5ml/min, the sample injection amount is 1 mu L, the split ratio is 30:1, and the chromatographic column adopts the following temperature programming: the initial temperature is 60 ℃, after the temperature is kept for 2 minutes, the temperature is increased to 230 ℃ at 10 ℃/min, and the temperature is kept for 2 minutes;
(3) Setting mass spectrum conditions: EI ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode of full scanning, scanning range of 35-500amu, quadrupole temperature 160 ℃, transmission line temperature 270 ℃, solvent delay of 8min;
(4) And (3) sample injection detection: and (3) injecting a sample working solution into a gas chromatograph-mass spectrometer, and effectively separating a nicotine main peak and four impurity peaks, wherein the main peak and the four impurity peaks are shown in fig. 6-9.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (3)
1. A GC-MS detection assay method for synthesizing nicotine, characterized in that: the method comprises the following steps:
step one: taking a certain amount of nicotine prepared by the synthesis method, adding a solvent for dilution, and carrying out ultrasonic vibration for 3-5min to obtain a sample working solution, wherein the mass ratio of a nicotine sample to the solvent is 1:3-8;
step two: injecting a sample working solution into a gas chromatography-mass spectrometer, wherein the gas chromatography conditions are as follows: the chromatographic column adopts a polyethylene glycol capillary column with the length of 30m, the inner diameter of the column is 0.18mm, the film thickness is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999 percent, the carrier gas flow rate is 1.0-1.5ml/min, the sample injection amount is 1 mu L, and the split ratio is 30-60:1; the mass spectrum conditions are as follows: EI ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode of full scanning, scanning range of 35-500amu, quadrupole temperature 160 ℃, transmission line temperature 270 ℃, solvent delay of 8min; the obtained map carries out qualitative analysis on each impurity in the synthesized nicotine through the parameters of retention time, fragment peak shape and molecular weight;
the chromatographic column was warmed using the following program:
the initial temperature is 70 ℃, after the temperature is kept for 2 minutes, the temperature is increased to 260 ℃ at 10 ℃/min, and the temperature is kept for 4 minutes;
or (b)
The initial temperature is 60 ℃, after the temperature is kept for 2 minutes, the temperature is increased to 230 ℃ at 10 ℃/min, and the temperature is kept for 2 minutes;
the first impurity in the obtained map is dichloromethane, the second impurity is N-methyl pseudoscouring, and the fourth impurity is myosmine.
2. The method for GC-MS detection analysis of synthetic nicotine according to claim 1, wherein: the solvent in the first step is any one of ethanol, isopropanol and n-hexane.
3. The method for GC-MS detection analysis of synthetic nicotine according to claim 1, wherein: the polyethylene glycol capillary in the second step is any one of a stabilwax polyethylene glycol capillary, a BP-20 polyethylene glycol capillary and a carbowax polyethylene glycol capillary.
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Citations (3)
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| CN104330514A (en) * | 2014-11-05 | 2015-02-04 | 云南省烟草质量监督检测站 | Method for measuring nicotine purity by combination of gas chromatography-mass spectrometry method in combination with gas chromatographic method |
| CN107255687A (en) * | 2017-08-23 | 2017-10-17 | 国家烟草质量监督检验中心 | It is a kind of at the same determine nicotine in 11 kinds of secondary alkaloid impurity contents method |
| CN107290458A (en) * | 2017-08-23 | 2017-10-24 | 国家烟草质量监督检验中心 | It is a kind of while determining the method for 12 kinds of alkaloids in tobacco and tobacco product |
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| US7087106B2 (en) * | 2003-02-20 | 2006-08-08 | University Of Florida | Materials and methods for inhibiting fouling of surfaces exposed to aquatic environments |
| WO2018089871A1 (en) * | 2016-11-14 | 2018-05-17 | Tubular Solutions, Inc. | Method and apparatus for digital thread inspection |
| JP6907862B2 (en) * | 2017-09-28 | 2021-07-21 | 日本製鉄株式会社 | Internal surface inspection device for pipes |
| CN111350901B (en) * | 2020-03-20 | 2021-02-12 | 北京理工大学 | Measuring device for size precision of inner wall of long pipeline and surface defects of inner wall |
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| CN104330514A (en) * | 2014-11-05 | 2015-02-04 | 云南省烟草质量监督检测站 | Method for measuring nicotine purity by combination of gas chromatography-mass spectrometry method in combination with gas chromatographic method |
| CN107255687A (en) * | 2017-08-23 | 2017-10-17 | 国家烟草质量监督检验中心 | It is a kind of at the same determine nicotine in 11 kinds of secondary alkaloid impurity contents method |
| CN107290458A (en) * | 2017-08-23 | 2017-10-24 | 国家烟草质量监督检验中心 | It is a kind of while determining the method for 12 kinds of alkaloids in tobacco and tobacco product |
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| Alkaloids of Tobacco Smoke. I. Fractionation of Some Tobacco Alkaloids and of the Alkaloid Extract of Burley Cigarette Smoke by Gas Chromatography;LOUIS D. QUIN;《ALKALOIDS OF TOBACCO SMOKE I》;19590630;911-914 * |
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