CN113009046A - GC-MS-MS detection and analysis method for synthesizing nicotine - Google Patents
GC-MS-MS detection and analysis method for synthesizing nicotine Download PDFInfo
- Publication number
- CN113009046A CN113009046A CN202110341578.3A CN202110341578A CN113009046A CN 113009046 A CN113009046 A CN 113009046A CN 202110341578 A CN202110341578 A CN 202110341578A CN 113009046 A CN113009046 A CN 113009046A
- Authority
- CN
- China
- Prior art keywords
- nicotine
- impurity
- detection
- steps
- analysis method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- 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
-
- 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
-
- 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
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
A GC-MS-MS detection analysis method for synthesizing nicotine comprises the following steps: the method comprises the following steps: taking a certain amount of nicotine prepared by a synthesis method, adding a solvent for dilution, wherein the mass ratio of a nicotine sample to the solvent is 1:3-8, and obtaining a sample working solution after ultrasonic oscillation for 3-5 min; step two: and injecting the sample working solution into a gas chromatography-mass spectrometer, and carrying out qualitative analysis on each impurity in the synthesized nicotine by the obtained spectrum through the parameters of retention time, fragment peak shape and molecular weight. The detection method is simple, has accurate result, and is suitable for analyzing the impurity components of the synthesized nicotine; the method effectively separates main impurities in the synthesized nicotine and determines the structure of the main impurities by using a gas chromatography-mass spectrometry combined method, fills the blank of the field, and is beneficial to the popularization and development of the nicotine synthesis industry.
Description
Technical Field
The invention belongs to the field of detection of synthetic nicotine, and particularly relates to a GC-MS-MS detection analysis method of synthetic nicotine.
Background
Nicotine is a liquid alkaloid, has strong physiological activity, and has wide application in the fields of agriculture, medical intermediates and electronic cigarettes. The method for obtaining nicotine is mainly divided into plant extraction method and artificial synthesis method. The plant extraction method has mature process, the impurities mainly comprise known alkaloids such as anabasine, harmine, nicotinoline and the like, and related reports on impurity analysis are more.
The synthesis method mainly adopts ethyl nicotinate and N-vinyl pyrrolidone as raw materials, and nicotine is obtained by alkali-catalyzed claisen condensation, acidic decarboxylation cyclization, hydrogenation reduction, Eschweiler-Clarke methylation, resolution and refining (the reaction formula is shown in figure 10). In recent years, importance has been attached to synthetic methods because production is not limited by raw materials such as tobacco. However, no detection method suitable for synthesizing nicotine exists at present, and the impurity components and structures are not clear.
Disclosure of Invention
The invention provides a GC-MS-MS detection and analysis method for synthesizing nicotine, which is used for overcoming the defects in the prior art.
The invention is realized by the following technical scheme:
a GC-MS-MS detection analysis method for synthesizing nicotine comprises the following steps:
the method comprises the following steps: taking a certain amount of nicotine prepared by a synthesis method, adding a solvent for dilution, wherein the mass ratio of a nicotine sample to the solvent is 1:3-8, and obtaining a sample working solution after ultrasonic oscillation for 3-5 min;
step two: injecting a sample of 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, the length is 30m, the inner diameter of the column is 0.18mm, the thickness of the membrane is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999 percent, the flow rate of the carrier gas 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: IE ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode is full scanning, scanning range is 35-500amu, quadrupole rod temperature 160 ℃, transmission line temperature 270 ℃, solvent delay 8 min; the obtained spectrum qualitatively analyzes each impurity in the synthesized nicotine through parameters of retention time, fragment peak shape and molecular weight.
In the GC-MS-MS detection and analysis method for synthesizing nicotine, the solvent in the first step is any one of ethanol, isopropanol and n-hexane.
In the GC-MS-MS detection analysis method for synthesizing nicotine, 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.
In the GC-MS-MS detection analysis method for synthesizing nicotine, the initial temperature of the chromatographic column in the second step is 60-100 ℃, the initial temperature is kept for 2min, the temperature is raised to 230-280 ℃ at the speed of 10 ℃/min, and the initial temperature is kept for 2-6 min.
In the GC-MS-MS detection analysis method for synthesizing nicotine, the impurity in the spectrum obtained in the third step is dichloromethane. By comparing the mass spectrogram database with the impurity with the mass molecular weight of 85, the molecular ion peak [ M + H ]]+At 86, the impurity was inferred to be methylene chloride (formula shown in FIG. 11) from solvent residues in the process route.
According to the GC-MS-MS detection and analysis method for synthesizing nicotine, the impurity II in the spectrum obtained in the third step is N-methylanabasine. Comparing the impurity molecular ion peak M with a mass spectrogram database+The molecular weight is 176, the maximum fragment peak molecular weight is 161, therefore, the impurity contains methyl, and the impurity is deduced to be N-methyl anabasine (the molecular formula is shown in figure 12) by combining a nicotine synthesis process, and the impurity comes from the rearrangement and recarburization reaction of five-membered heterocycle into six-membered heterocycle due to the excessive methylation in the Eschweiler-Clarke reaction process.
In the GC-MS-MS detection and analysis method for synthesizing nicotine, the impurity III in the spectrum obtained in the third step is 2-isopropyl-4-hydroxy-1, 5 naphthyridine. Comparing the impurity molecule ion peak M with the mass spectrogram database+The molecular weight is 188, and the impurity is 2-isopropyl-4-hydroxy-1, 5 naphthyridine (the molecular formula is shown in figure 13).
In the GC-MS-MS detection analysis method for synthesizing nicotine, impurity IV in the spectrum obtained in the third step is Mysmine. Comparing the impurity molecular ion peak M with a mass spectrogram database+Molecular weightAt 146, the impurity was deduced to be mesmin (formula shown in figure 14) from the two-step intermediate residue in the synthetic route.
The invention has the advantages that: the detection method is simple, has accurate result, and is suitable for analyzing the impurity components of the synthesized nicotine; the method effectively separates main impurities in the synthesized nicotine and determines the structure of the main impurities by using a gas chromatography-mass spectrometry combined method, fills the blank of the field, and is beneficial to the popularization and development of the nicotine synthesis industry.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
Fig. 1 is a TIC diagram of the total particle flow of the synthetic nicotine of the present invention, which shows that the synthetic nicotine has four main impurities except nicotine: impurity one (5.8995min), impurity two (20.5923min), impurity three (22.1346min) 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 two 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 two of example 2 of the present invention;
FIG. 8 is a mass spectrum of impurity three 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 of a prior art synthesis of nicotine;
FIG. 11 is a molecular formula of a first impurity identified in the assay of synthetic nicotine according to the present invention;
FIG. 12 is a molecular formula of a second impurity identified by assaying synthetic nicotine in accordance with the present invention;
FIG. 13 is a molecular formula of a third impurity identified in the assay of synthetic nicotine according to the present invention;
FIG. 14 is a molecular formula of a fourth impurity identified by assays of synthetic nicotine in accordance with the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. 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
(1) Preparing a sample working solution: taking 0.5g of nicotine prepared by a synthesis method, adding 3.0g of normal hexane for dilution, and obtaining a sample working solution after ultrasonic oscillation for 5 min;
(2) setting gas chromatography conditions: the chromatographic column adopts a polyethylene glycol capillary column, the type is BP-20 of the invention, the length is 30m, the inner diameter of the column is 0.18mm, the thickness of the membrane is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999 percent, 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 maintained for 2 minutes, the temperature is raised to 260 ℃ at the speed of 10 ℃/min, and the temperature is maintained for 4 minutes;
(3) setting mass spectrum conditions: IE ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode is full scanning, scanning range is 35-500amu, quadrupole rod temperature 160 ℃, transmission line temperature 270 ℃, solvent delay 8 min;
(4) sample introduction detection: the working solution of the sample is injected into the gas chromatography-mass spectrometer, and the main peak of nicotine and four impurity peaks are effectively separated, as shown in fig. 2-5.
Example 2
(1) Preparing a sample working solution: taking 0.5g of nicotine prepared by a synthesis method, adding 2.0g of ethanol for dilution, and obtaining a sample working solution after ultrasonic oscillation for 5 min;
(2) setting gas chromatography conditions: the chromatographic column adopts a polyethylene glycol capillary column, the type is a stabilwax of the invention, the length is 30m, the inner diameter of the column is 0.18mm, the thickness of the membrane is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999 percent, the flow rate of the carrier gas 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 maintained for 2 minutes, the temperature is raised to 230 ℃ at the speed of 10 ℃/min, and the temperature is maintained for 2 minutes;
(3) setting mass spectrum conditions: IE ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode is full scanning, scanning range is 35-500amu, quadrupole rod temperature 160 ℃, transmission line temperature 270 ℃, solvent delay 8 min;
(4) sample introduction detection: the working solution of the sample is injected into the gas chromatography-mass spectrometer, and the main peak of nicotine and four impurity peaks are effectively separated, as shown in fig. 6-9.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present 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 solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (8)
1. A GC-MS-MS detection analysis method for synthesizing nicotine is characterized in that: the method comprises the following steps:
the method comprises the following steps: taking a certain amount of nicotine prepared by a synthesis method, adding a solvent for dilution, wherein the mass ratio of a nicotine sample to the solvent is 1:3-8, and obtaining a sample working solution after ultrasonic oscillation for 3-5 min;
step two: injecting a sample of 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, the length is 30m, the inner diameter of the column is 0.18mm, the thickness of the membrane is 0.18 mu m, the carrier gas is helium, the purity is more than or equal to 99.999 percent, the flow rate of the carrier gas 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: IE ion source, ion source temperature 260 ℃, ionization energy 75eV, scanning mode is full scanning, scanning range is 35-500amu, quadrupole rod temperature 160 ℃, transmission line temperature 270 ℃, solvent delay 8 min; the obtained spectrum qualitatively analyzes each impurity in the synthesized nicotine through parameters of retention time, fragment peak shape and molecular weight.
2. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: the solvent in the first step is any one of ethanol, isopropanol and n-hexane.
3. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: and 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.
4. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: in the second step, the initial temperature of the chromatographic column is 60-100 ℃, the chromatographic column is kept for 2min, the temperature is raised to 230-280 ℃ at the speed of 10 ℃/min, and the chromatographic column is kept for 2-6 min.
5. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: and the first impurity in the spectrum obtained in the third step is dichloromethane.
6. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: and D, obtaining an impurity II in the spectrum obtained in the step three, wherein the impurity II is N-methylanabasine.
7. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: and III, which is an impurity in the spectrum obtained in the third step, is 2-isopropyl-4-hydroxy-1, 5 naphthyridine.
8. The GC-MS-MS detection and analysis method of synthetic nicotine as claimed in claim 1, wherein said method comprises the steps of: and the impurity IV in the map obtained in the step three is the Mesamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110341578.3A CN113009046B (en) | 2021-03-30 | 2021-03-30 | GC-MS-MS detection and analysis method for synthesizing nicotine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110341578.3A CN113009046B (en) | 2021-03-30 | 2021-03-30 | GC-MS-MS detection and analysis method for synthesizing nicotine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113009046A true CN113009046A (en) | 2021-06-22 |
| CN113009046B CN113009046B (en) | 2023-10-17 |
Family
ID=76409360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110341578.3A Active CN113009046B (en) | 2021-03-30 | 2021-03-30 | GC-MS-MS detection and analysis method for synthesizing nicotine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113009046B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040235901A1 (en) * | 2003-02-20 | 2004-11-25 | Kem William Reade | Materials and methods for inhibiting fouling of surfaces exposed to aquatic environments |
| 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 |
| US20180135974A1 (en) * | 2016-11-14 | 2018-05-17 | Tubular Solutions, Inc. | Method and Apparatus for Digital Thread Inspection |
| JP2019060825A (en) * | 2017-09-28 | 2019-04-18 | 新日鐵住金株式会社 | Internal surface inspection device for tube |
| CN111350901A (en) * | 2020-03-20 | 2020-06-30 | 北京理工大学 | Measuring device for size precision of inner wall of long pipeline and surface defects of inner wall |
-
2021
- 2021-03-30 CN CN202110341578.3A patent/CN113009046B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040235901A1 (en) * | 2003-02-20 | 2004-11-25 | Kem William Reade | Materials and methods for inhibiting fouling of surfaces exposed to aquatic environments |
| 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 |
| US20180135974A1 (en) * | 2016-11-14 | 2018-05-17 | Tubular Solutions, Inc. | Method and Apparatus for Digital Thread Inspection |
| 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 |
| JP2019060825A (en) * | 2017-09-28 | 2019-04-18 | 新日鐵住金株式会社 | Internal surface inspection device for tube |
| CN111350901A (en) * | 2020-03-20 | 2020-06-30 | 北京理工大学 | Measuring device for size precision of inner wall of long pipeline and surface defects of inner wall |
Non-Patent Citations (6)
Also Published As
| Publication number | Publication date |
|---|---|
| CN113009046B (en) | 2023-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Harmon et al. | The structure of rohitukine, the main alkaloid of Amoora rohituka (syn. Aphanamixis polystachya)(Meliaceae) | |
| Witte et al. | Investigation of the alkaloid pattern of Datura innoxia plants by capillary gas-liquid-chromatography-mass spectrometry | |
| Rodríguez-Sánchez et al. | A derivatization procedure for the simultaneous analysis of iminosugars and other low molecular weight carbohydrates by GC–MS in mulberry (Morus sp.) | |
| Wender et al. | General methodology for cis-hydroisoquinoline synthesis: synthesis of reserpine | |
| CN113009046A (en) | GC-MS-MS detection and analysis method for synthesizing nicotine | |
| CN103472165B (en) | Detection method used for rapid identification of paris polyphylla var. yunnanensis saponin composition, and applications thereof | |
| CN114392287B (en) | Pine needle extract for inhibiting activity of 5 alpha reductase as well as preparation method and application thereof | |
| Tang et al. | Total synthesis of (+-)-camptothecin | |
| CN111398498B (en) | Application of indole-3-methyl acetate in identifying apis cerana honey and apis mellifera honey | |
| Julien‐Larose et al. | Quantification of ketotifen and its metabolites in human plasma by gas chromatography mass spectrometry | |
| Fleurant et al. | Enantioselective synthesis of (5R, 9R)-5-propyl-octahydroindolizine [(−)-gephyrotoxin 167B] | |
| Auriola et al. | Analysis of tropane alkaloids with thermospray high-performance liquid chromatography—mass spectrometry | |
| Muller et al. | Identification of 4-ethoxy-4-hydroxybutric acid. gamma.-lactone [5-ethoxydihydro-2 (3H)-furanone] as an aroma component of wine from Vitis Vinifera Ruby Cabernet | |
| CN112114079A (en) | Method for simultaneously detecting 9 chemical components in quisqualis indica | |
| Sun et al. | A synthesis of (+) and (–) methyl nonactate from a derivative of D-ribose | |
| Delgado et al. | Terpenoids from Viguiera excelsa and Viguiera oaxacana | |
| McLean et al. | The constituents of Nauclea diderrichii. Part II. isolation and classification of constituents; simple β-carboline and pyridine alkaloids | |
| Ayer et al. | The total synthesis of coccinelline and precoccinelline | |
| Blay et al. | Analysis of taxol and related taxanes from Taxus canadensis using liquid chromatography combined with mass spectrometry or tandem mass spectrometry | |
| Offen et al. | 4, 5-Dimethylthiazole-N-oxide-S-oxide: a metabolite of chlormethiazole in man | |
| Bellesia et al. | The biosynthesis of dolichodial in Teucrium marum | |
| CN110031556B (en) | Method for rapidly identifying lipstatin metabolites in streptomyces toxytricini fermentation products | |
| CN109115903B (en) | A method of witchweed lactone analogue is detected using capillary electrophoresis-laser-induced fluorescence | |
| Byrd et al. | Stereochemistry of addition reactions of allenes. V. Stereoselective bromination of 1, 2-cyclononadiene | |
| Bishop et al. | Identification of acetylcholine and propionylcholine in bull spermatozoa by integrate pyrolysis, gas chromatography and mass spectrometry |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |