CN113675070A - Mass spectrum source internal dissociation method and device based on plasma principle - Google Patents
Mass spectrum source internal dissociation method and device based on plasma principle Download PDFInfo
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Abstract
The invention discloses a mass spectrum source internal dissociation method and device based on a plasma principle. The method and the device provided by the invention can utilize the plasma to dissociate the compound, can simultaneously obtain charges, free radicals and plasma chemically induced fragment ions, have various types and rich information of the obtained mass spectrogram fragment ions, can comprehensively reflect the structural information of the compound in a sample, can realize the qualitative analysis of the compound, and even can realize the qualitative identification of two isomers; in addition, the device disclosed by the invention can be used under the normal pressure condition without a vacuum environment, has the advantages of simple structure, simplicity and convenience in operation, low cost and easiness in implementation, can be conveniently combined with a common atmospheric pressure ionization technology and a mass spectrometer, and can effectively make up for the defect that the atmospheric pressure ionization technology is used for qualitative analysis.
Description
Technical Field
The invention relates to a mass spectrum source internal dissociation method and device based on a plasma principle, and belongs to the technical field of mass spectrum analysis.
Background
Mass Spectrometry (MS) is an important analytical tool that can analyze complex mixtures, providing information about molecular weight, elemental composition, and chemical structure of the analyte, with a high degree of specificity and sensitivity. The basic principle of mass spectrometry is to ionize each component in a sample in an ion source to generate ions with different charge-mass ratios and positive charges, form an ion beam under the action of an accelerating electric field, enter a mass analyzer, and then in the mass analyzer, generate opposite velocity dispersion by using an electric field and a magnetic field, focus the two components respectively to obtain a mass spectrogram, thereby determining the mass of the sample. Therefore, ionization techniques have a significant impact on mass spectrometry results. In recent years, with continuous innovation and improvement of compound desorption and ionization technologies and mass analyzers, mass spectrometry becomes one of the most rapidly developed analysis technologies, and at present, the mass spectrometry technology is more and more widely applied in the fields of chemistry and chemical industry, biology and life sciences, medicine, pharmacy, material science, environmental protection and the like.
Atmospheric pressure ionization technology (API) is a kind of soft ionization mode, mainly including electrospray ionization (ESI), Ion Spray Ionization (ISI) and Atmospheric Pressure Chemical Ionization (APCI). Since the generation of atmospheric pressure ionization techniques represented by ESI, the combination of mass spectrometry techniques with many separation techniques has become mature and has played an increasingly important role in many fields. The classical paradigm for the success of such combinations is liquid chromatography-mass spectrometry (LC-MS). Compared with gas chromatography-mass spectrometry (GC-MS), the LC-MS uses API technologies such as ESI and the like, so that the hardware and technical requirements of mass spectrometry and chromatography are greatly reduced, and the method is more suitable for analyzing compounds which are unstable in heat, difficult to volatilize, difficult to derivatize and large in molecular weight. Therefore, the combination of the mass spectrum with high sensitivity and high selectivity and the liquid chromatography with excellent separation capability can effectively solve the analysis problem of complex samples, even biological samples with extremely low concentration and complex matrixes. Therefore, LC-MS is widely applied in the fields of environmental monitoring, drug research and development, forensic identification and the like, becomes the most effective analytical technical means at present, greatly promotes the development of advanced subjects such as proteomics, metabonomics and the like, and makes outstanding contributions in the aspects of protein identification, biomarker discovery, in-vivo metabolic pathway elucidation and the like.
After the classical atmospheric pressure ionization techniques such as ESI used in LC-MS, various novel API techniques emerge endlessly, greatly enriching the variety of mass spectrometry ionization techniques. The novel API can realize direct analysis of samples under normal pressure environment, does not need or only needs little sample pretreatment, is very convenient for development, modification and separation technology combination, and is a research hotspot in the field of mass spectrometry. Numerous mass spectrometers at home and abroad have made a great contribution in this field. Only domestically, various API technologies typified by extractive electrospray technology (EESI), probe electrospray ionization technology (PESI), aerodynamic assisted ionization technology (AF-AI), dielectric barrier discharge ionization technology (DBDI), low temperature plasma technology (LTP), carbon fiber ionization technology (CFI), and the like have been developed. The technologies have shown good application prospects in the fields of explosive detection, biological samples, organic reaction monitoring and the like.
Although atmospheric pressure ionization techniques offer great advantages in terms of ease of use in conjunction with separation techniques and address many analytical problems with such advantages, they have significant drawbacks for mass spectrometric qualitative analysis compared to classical ion sources (e.g., EI) that require high vacuum environments. The defects are mainly caused by that the ionization mechanism of the atmospheric pressure ionization source generally belongs to a soft ionization process, and most of the compounds are obtained by the soft ionization process as even electron ions, so that odd electron ions are difficult to obtain; meanwhile, the energy of the atmospheric pressure ionization process is limited, few fragments of the obtained compound are obtained, the structural information of the target compound cannot be comprehensively reflected, and a compound spectrogram database based on the atmospheric pressure ionization technology cannot be formed. Just because LC-MS uses ESI, APCI and other soft ionization technologies, it is influenced by ionization mode and mobile phase difference, and compared with GC-MS, it has a great defect, i.e. low reproducibility, no standard spectrum library.
At present, mass spectrum dissociation technologies of various mature systems are applied to tandem mass spectrometry, and the mass spectrum dissociation technologies help to form fragment ions to realize more accurate qualitative analysis on an analysis object. The following are more common:
1) the most widely used Collision Induced Dissociation (CID): the technology can be applied to various mass spectrometers and the like such as ion trap mass spectrum, triple quadrupole mass spectrum, quadrupole time-of-flight mass spectrum and Fourier transform, and CID utilizes the chemical inert collision gas (such as Ar, He and N) in the parent ions and the collision pool2、CO2Etc.) repeated collision, so that molecules accumulate energy, when the energy accumulation reaches a fragmentation threshold, partial chemical bonds in parent ions are broken to generate daughter ions, but the nature of CID is chemical dissociation, the energy is limited, when the method is used for being used with API (application program interface) which can only generate even electron ions, for selected even electron parent ions, only a dissociation process induced by charges can be generated usually to obtain even electron ion fragments, odd electron ion fragments are difficult to obtain, and the structural information of compounds reflected by a series mass spectrogram is still limited;
2) in-source collision induced dissociation (In-source CID) technique: the technology utilizes higher cone voltage in an ion source to increase the kinetic energy obtained by sample molecules, in an ion acceleration area, the vacuum degree is relatively low (usually 10 < -1 > Pa), ions collide with neutral molecules to generate fragment ions, so that in-source dissociation of the sample molecules is realized, and meanwhile, molecular weight information and structural information of the sample are obtained, but the in-source CID is mainly in a neutral loss dissociation mode and cannot obtain enough abundant fragment information;
3) high energy induced lysis (HCD): HCD cracking is to carry out high-energy cracking in a specific HCD cracking pool after ion capture and selection are carried out through an ion trap, compared with CID, HCD provides a stable high-energy cracking mode, the phenomenon of low-mass fragment loss in CID can be improved, the number of fragments is increased, but HCD needs to work in a high-vacuum instrument environment, the requirement on equipment is high, and therefore certain limitation is brought to application;
4) electron Capture Dissociation (ECD): the electron gun needs to work in a high vacuum instrument environment, and has application limitation like the HCD.
In summary, the existing mass spectrometry tandem dissociation technology cannot be conveniently used with API, or cannot obtain a dissociation spectrum containing sufficient fragment information after being used. Therefore, the defects of the API used for qualitative analysis are not fundamentally solved and compensated.
The plasma is the fourth state of matter except solid, liquid and gas, has been widely applied in daily life and production of people since the discovery of the 19 th century, and the deep research on the application and properties of the basic principle is always a hotspot in the scientific research field. In the field of mass spectrometry, plasma is mainly applied to an ambient ionization technique, for example, Dielectric Barrier Discharge Ionization (DBDI), Low Temperature Plasma (LTP), microwave plasma torch dissociation (MPT), and other ambient ionization techniques based on the plasma desorption principle. The research direction of these ionization technologies based on the plasma principle mainly aims at improving the ionization efficiency of compounds, that is, obtaining mass spectrometry spectra with only molecular ion peaks as much as possible, while the dissociation phenomenon of compounds caused by plasma is a problem that researchers try to avoid, and researchers generally think that the dissociation of compounds greatly complicates mass spectra and is a negative factor for mass spectrometry. This results in that current plasma-based mass spectrometry can only be used to obtain molecular weight and molecular formula information of the compound to be tested, and the information provided by mass spectrometry is relatively lacking in structural information of the object to be analyzed, and is insufficient in qualitative analysis.
Disclosure of Invention
In view of the above problems in the prior art, it is an object of the present invention to provide a method and apparatus for mass spectrometry source dissociation based on the plasma principle.
In order to solve the problems, the invention adopts the following technical scheme:
a mass spectrum source internal dissociation method based on a plasma principle is characterized in that an ionized or unionized sample is continuously contacted with plasma for 1-3 minutes, so that the sample is dissociated.
In one embodiment, the temperature of the plasma is 400-800 ℃.
In one embodiment, the plasma is an arc or flame.
In one embodiment, the ionized sample is a sample obtained by ionizing by an atmospheric pressure ionization technique.
A mass spectrum source internal dissociation device based on a plasma principle comprises a plasma generation device, a mass spectrum sample inlet and a sample introduction device for introducing ionized or unionized samples, wherein the plasma generation device is positioned in front of the mass spectrum sample inlet, and an outlet end or a loaded sample end of the sample introduction device is positioned near the plasma generation device.
In one embodiment, the plasma generating device is an arc discharge device or a flame generating device.
The electric arc discharge device comprises a voltage input module and two voltage output ends, wherein a wire is connected between the voltage input module 7 and the voltage output ends, the input voltage of the voltage input module is 15-25 kV, and the distance between the two voltage output ends is 7-10 mm.
According to a preferable scheme, the temperature of the flame generated by the flame generating device is 400-800 ℃.
In a preferred embodiment, when the sample introduced by the sample introduction device is an ionized sample, the sample introduction device is an atmospheric pressure ionization device, and the outlet end of the ionized sample of the atmospheric pressure ionization device is located near the plasma generation device, for example, an electrospray ionization device, and the outlet end of an electrospray needle in the electrospray ionization device is located near the plasma generation device.
In a preferred embodiment, when the sample introduced by the sample introduction device is an unionized sample, the sample introduction device is a direct sample introduction device, and the direct sample introduction device includes, but is not limited to, tweezers, a sample rod, a capillary, an ultrasonic atomization sheet, an atomizer, a sampling probe, and a needle without voltage.
In one embodiment, the distance between the plasma area generated by the plasma generating device and the mass spectrum sample inlet is 5-15 mm.
Compared with the prior art, the invention has the beneficial technical effects that:
the method and the device for dissociation in the mass spectrum source based on the plasma principle can utilize the plasma to dissociate the compound, can simultaneously obtain charges, free radicals and plasma chemically induced fragment ions, have various types and rich information of the fragment ions of the mass spectrum, can comprehensively reflect the structural information of the compound in a sample, can realize the qualitative analysis of the compound, and even can realize the qualitative analysis of two isomers; in addition, the device can be used under the normal pressure condition without a vacuum environment, has simple structure, simple and convenient operation, low cost and easy realization, can be conveniently combined with common atmospheric pressure ionization technologies (such as electrospray, paper spray and the like) and mass spectrometers (such as triple quadrupole mass spectrometer, time-of-flight mass spectrometer, ion trap mass spectrometer and the like), can effectively make up the defect that the atmospheric pressure ionization technology is used for qualitative analysis, and has extremely wide application prospect.
Drawings
FIG. 1 is a schematic structural diagram of a mass spectrometry source dissociation apparatus based on the plasma principle according to the present invention;
FIG. 2 is a schematic diagram of a mass spectrometer source internal dissociation device based on plasma principles in combination with electrospray ionization techniques according to the present invention;
FIG. 3 is a schematic diagram of an arc discharge plasma as a plasma in the dissociation apparatus in a mass spectrometry source based on the plasma principle provided by the present invention;
FIG. 4 is a schematic diagram of a plasma in the dissociation apparatus in a mass spectrometry source based on the plasma principle according to the present invention;
FIG. 5 is a standard EI mass spectrum of fentanyl;
FIG. 6 is [ M + H ] for fentanyl]+ESI-CID series mass spectrum of (A);
FIG. 7 is a mass spectrum of fentanyl dissociation obtained by the mass spectrometry in-source dissociation device of the present invention (the sample introduction device is a direct sample introduction device);
FIG. 8 is a standard EI mass spectrum of phenylbutazone;
FIG. 9 is [ M + H ] of phenylbutazone]+ESI-CID series mass spectrum of (A);
FIG. 10 is a mass spectrum of phenylbutazone obtained from a mass spectrometer source dissociation device (the sample introduction device is an electrospray ionization device) according to the present invention;
FIG. 11 is [ M + H ] of methamphetamine]+ESI-CID series mass spectrum of (A);
FIG. 12 is [ M + H ] of amphetamine]+ESI-CID series mass spectrum of (A);
FIG. 13 is a mass spectrum of a dissociation of methamphetamine obtained by the mass spectrometry source dissociation device of the present invention (the sample introduction device is a direct sample introduction device);
FIG. 14 is a mass spectrum of amphetamine dissociation obtained with the mass spectrometer source dissociation device of the present invention (the sample introduction device is a direct sample introduction device);
FIG. 15 is [ M + H ] of methyl salicylate]+ESI-CID series mass spectrum of (A);
FIG. 16 is [ M + H ] of 3-methylsalicylic acid]+ESI-CID series mass spectrum of (A);
FIG. 17 is a mass spectrum of methyl salicylate obtained by the mass spectrometer in-source dissociation device (the sample introduction device is a direct sample introduction device) of the present invention;
FIG. 18 is a mass spectrum of 3-methylsalicylic acid obtained from a mass spectrometer in-source dissociation device (the sample introduction device is a direct sample introduction device) according to the present invention;
the numbers in the figures are as follows: 1. a plasma generating device; 2. a mass spectrum sample inlet; 3. a sample introduction device; 4. an outlet or loaded sample end of the sample introduction device; 5. plasma; 6. an electric arc; 7. a voltage input module; 8. a voltage output terminal; 9. a wire; 10. a flame; 11. a flame generating tube; 12. an electrospray needle; 13. voltage applied to the electrospray needle; 14. an ionized sample.
Detailed Description
The technical scheme of the invention is further described in detail and completely by combining the attached drawings.
As shown in fig. 1 to 4: the invention provides a mass spectrum source internal dissociation device based on a plasma principle, which comprises a plasma generating device 1, a mass spectrum sample inlet 2 and a sample introducing device 3 for introducing ionized or unionized samples, wherein the plasma generating device 1 is positioned in front of the mass spectrum sample inlet 2, and an outlet end or a loaded sample end 4 of the sample introducing device 3 is positioned near the plasma generating device 1.
The device can be compatible with common mass spectrometers (such as triple quadrupole mass spectrometers, time-of-flight mass spectrometers, ion trap mass spectrometers and the like), can also be popularized and applied to other mass spectrometry, can be used with the common mass spectrometers when being used for mass spectrometry, and has wide application range and strong practicability.
The method for realizing the dissociation in the mass spectrum source by adopting the mass spectrum source dissociation device based on the plasma principle of the invention is to continuously contact ionized or unionized samples with plasmas for 1-3 minutes so as to dissociate the samples. Specifically, referring to fig. 1, an ionized or unionized sample is first introduced by sample introduction means 3; starting the plasma generating device 1 to generate plasma (because the plasma generating device 1 is located in front of the mass spectrum sample inlet 2, namely, a plasma area is generated in front of the mass spectrum sample inlet 2); after an ionized or non-ionized sample is introduced into the plasma region, the ionized or non-ionized sample is continuously contacted with the plasma 5 for 1-3 minutes, the sample is dissociated under the action of the plasma ions to generate fragment ions, and the generated fragment ions enter the mass spectrometer through the mass spectrum injection port 2, so that mass spectrum analysis of the sample can be realized. The plasma is rich in active species and energy, so that a sample in contact with the plasma can be ionized, and the sample can be continuously in contact with the plasma for 1-3 minutes, so that the sample can simultaneously generate charges, free radicals and a plasma chemical induced compound dissociation process, and therefore, not only can a molecular ion peak be obtained, but also charges, free radicals and plasma chemical induced fragment ions can be simultaneously obtained, the obtained mass spectrum fragment ions are various in types and rich in information, the structural information of the compound in the sample can be comprehensively reflected, and the qualitative analysis of the compound can be realized.
In the invention, the temperature of the plasma is 400-800 ℃, so that ionization and dissociation of most samples can be met, the samples can be prevented from being oxidized, degraded, polymerized and the like due to overhigh temperature, and the ionization and dissociation effects of the samples are effectively ensured. The plasma generating device 1 is an arc discharge device or a flame generating device.
As shown in fig. 3, when the plasma generating device 1 is an arc discharge device, the plasma is an arc 6, the arc discharge device shown in fig. 3 includes a voltage input module 7 and two voltage output ends 8, and a conducting wire 9 is connected between the voltage input module 7 and the voltage output ends 8, wherein the input voltage in the voltage input module 7 is 15-25 kV, and the distance between the two voltage output ends 8 is 7-10 mm, so that the temperature of the arc 6 (i.e., the plasma) generated by the arc discharge device is 400-800 ℃.
As shown in fig. 4, when the plasma generating device 1 is a flame generating device, the plasma is a flame 10, in fig. 4, the flame generating device is a flame generating pipe 11, the flame generating pipe 11 is connected with a gas fuel supply device (not shown), when in use, the gas fuel is input into the flame generating pipe 11 through the gas fuel supply device, and then the fuel is ignited at the outlet of the flame generating pipe 11, so that the flame 10 (i.e., the plasma) can be generated, and the used gas fuel includes, but is not limited to, hydrogen, methane, and the like, and preferably hydrogen. The temperature of the flame 10 is 400 to 800 ℃, and the temperature of the flame 10 can be adjusted by known means such as adjusting the flow rate of the gas fuel and selecting the type of the gas fuel.
In the present invention, as can be seen from the above, the sample introduced by the sample introduction means 3 may be an ionized sample or a conventional sample that is not ionized.
When the sample introduced by the sample introducing device 3 is an ionized sample, the sample introducing device 3 is an atmospheric pressure ionization device, and correspondingly, the ionized sample refers to a sample obtained by performing ionization treatment by an atmospheric pressure ionization technique, the atmospheric pressure ionization device includes but is not limited to an electrospray ionization device and a paper spray ionization device, and the sample introducing device 3 is an atmospheric pressure ionization device, which also represents that the mass spectrometry in-source dissociation device and method of the present invention can be used in combination with the atmospheric pressure ionization technique. When the sample introducing device 3 is an atmospheric pressure ionization device, in use, the outlet end of the ionized sample of the atmospheric pressure ionization device is located near the plasma generation device, specifically, as shown in fig. 2, the atmospheric pressure ionization device adopts an electrospray ionization device, the outlet end of an electrospray nozzle needle 12 in the electrospray ionization device is located near the plasma generation device 1, a voltage 13 is applied to the electrospray nozzle needle 12, the ionized sample 14 is sprayed to the plasma region of the plasma generation device 1 through the electrospray nozzle needle 12, and then dissociation further occurs under the action of plasma.
When the sample introduced by the sample introduction device 3 is a non-ionized sample, the sample introduction device 3 is a direct sample introduction device, which includes, but is not limited to, tweezers, a sample rod, a glass capillary, an ultrasonic atomization sheet, an atomizer, a sampling probe, and a needle without voltage. In the present embodiment, referring to fig. 1, 3 and 4, the sample introducing device 3 is a glass capillary, and in this case, reference numeral 4 in the figure represents a loaded sample end of the sample introducing device (glass capillary) 3, a conventional unionized sample can be loaded on the loaded sample end 4 of the sample introducing device (glass capillary), and the loaded sample end 4 is located near the plasma generating device 1, so that the sample can be sent to a plasma region of the plasma generating device 1, and then ionized and dissociated under the action of plasma.
In addition, in the invention, the distance d between the plasma region generated by the plasma generating device 1 and the mass spectrum sample inlet 2 is 5-15 mm, so as to ensure the mass spectrum analysis effect.
The technical effects achieved by the present invention will be further described below with reference to specific application examples.
Example 1
The mass spectrum source internal dissociation device based on the plasma principle and a mass spectrometer (a mass analyzer is a triple quadrupole) are adopted for psychoactive substance Fentanyl (Fentanyl)
(MW 336) mass spectrometry was performed:
the sample introduction device 3 is a glass capillary; the plasma 5 is an arc;
fentanyl was formulated into a sample solution of 20 μ g/mL using methanol solvent; introducing a sample by dipping in a glass capillary; the voltage input module 7 of the arc discharge device is opened, an arc 6 is generated between the two voltage output ends 8, the input voltage in the voltage input module 7 is 20kV, the distance between the two voltage output ends 8 is 8mm, a sample is continuously contacted with the arc 6 for 2 minutes, the sample is dissociated under the actions of heat, energy, chemical reactivity and the like of the arc 6 to generate fragment ions, the fragment ions enter the mass spectrometer through the mass spectrum sample inlet to realize detection, and the mass analyzer is enabled to be in a collection state all the time.
The same sample was also subjected to [ M + H ] on a commercial ESI ion source]+Tandem mass spectrometry.
FIG. 5 is a standard EI mass spectrum of fentanyl, from FIG. 5, it can be seen that the fragmentation of the compound induced by free radicals produced more fragments, but some of the fragment ions induced by charge were absent from the spectrum, and the molecular ion peak of the compound fentanyl was too low to be identified in the spectrum;
FIG. 6 is [ M + H ] for fentanyl]+The ESI-CID mass spectrum of FIG. 6 shows that the number of fragment ions is small and the fragment information is limited due to the lack of the radical-induced fragmentation process;
FIG. 7 shows the results obtained by using the mass spectrometer in-source dissociation device in this embodimentThe obtained dissociation mass spectrogram of fentanyl is shown in the figure, wherein the mass number marked with a round icon is the fragment ion matched with the EI spectrogram of the compound, and the mass number marked with a diamond is the mass number [ M + H ] of the compound]+The ESI-CID mass spectrogram of the fragment ions matched with the ESI-CID mass spectrogram of the dissociation device is marked with the mass number of the five-pointed star which is the fragment ions specific to the dissociation device, and the fact that the device and the method can obtain the fragment ions simultaneously containing charges, free radicals and plasma chemical induction is shown, the obtained mass spectrogram fragment ions are various in types and rich in information, and the structure information of the compound can be reflected most comprehensively; compared with EI, the device can be used in a normal pressure environment, and the obtained spectrogram compound has high excimer ion peak intensity and is well recognized, so that a more practical and effective method is provided for qualitative detection of the compound.
The present embodiment may also make the following evolution:
1) the sample introducing device 3 can be replaced by any one of tweezers, a sample rod, an ultrasonic atomization sheet, an atomizer, a sampling probe, a spray needle without voltage and an electrospray spray needle in an electrospray ionization device, and the rest conditions are unchanged;
2) the plasma 5 can be replaced by flame 10, the temperature of the flame 10 can be any value within the range of 400-800 ℃, and the rest conditions are unchanged;
3) the input voltage in the voltage input module 7 can be any value within the range of 15-25 kV, the distance between the two voltage output ends 8 can be any value within the range of 7-10 mm, and other conditions are unchanged;
4) the continuous contact time of the sample and the plasma can be any value within the range of 1-3 minutes, and the rest conditions are unchanged.
Example 2
The device for mass spectrum source internal dissociation based on the plasma principle and the mass spectrometer (the mass analyzer is a triple quadrupole) are adopted to excite an excitant compound Phenylbutazone
(MW 336) mass spectrometry was performed:
the sample introducing device 3 is an electrospray ionization device, in particular to an electrospray nozzle needle in the electrospray ionization device, and an ionized sample is introduced from an electrospray nozzle needle 12 in the electrospray ionization device; the plasma 5 is an arc;
preparing phenylbutazone into a sample solution to be detected, wherein the sample solution is 20 micrograms per mL by using a methanol solvent; a sample solution to be detected is ionized by an electrospray ionization device, and then an ionized sample is introduced from an electrospray spray needle 12 which is applied with voltage in the electrospray ionization device (the sample solution enters the electrospray spray needle 12 and is ionized); the voltage input module 7 of the arc discharge device is opened, an arc 6 is generated between the two voltage output ends 8, the input voltage in the voltage input module 7 is 15kV, the distance between the two voltage output ends 8 is 8mm, a sample is continuously contacted with the arc 6 for 3 minutes, the sample is dissociated under the actions of heat, energy, chemical reactivity and the like of the arc 6 to generate fragment ions, the fragment ions enter the mass spectrometer through the mass spectrum sample inlet to realize detection, and the mass analyzer is enabled to be in a collection state all the time.
The same sample was additionally subjected to tandem mass spectrometry of [ M + H ] + on a commercial ESI ion source.
FIG. 8 is a standard EI mass spectrum of phenylbutazone, which shows that although the number of fragments is large, the structural information of the compound is large, but some fragments generated by ESI-CID are lacked;
FIG. 9 is [ M + H ] of phenylbutazone]+The ESI-CID mass spectrum of (1) lacks fragment ions generated in a fragmentation process induced by free radicals, the number of the fragment ions is small on the whole, and the fragment information is limited;
FIG. 10 is a mass spectrum of the dissociation of phenylbutazone obtained by the mass spectrometer in-source dissociation device in this example, where the mass numbers marked with circles are fragment ions matching the EI spectrum of the compound, and the mass numbers marked with diamonds are [ M + H ] of the compound]+The fragment ions matched with the ESI-CID mass spectrogram, and the mass number marked with the five-pointed star are the fragment ions special for the dissociation device, which shows that the device and the method can obtain the fragment ions simultaneously containing charges, free radicals and plasma chemical inductionIn the compound dissociation process, the obtained mass spectrogram fragment ions have various types and rich information, and have the basis of constructing a spectrogram database; compared with EI, the dissociation technology can be used in an atmospheric environment, the effect of combining the dissociation technology with a classical atmospheric pressure ion source of electrospray is ideal, the combination of the dissociation technology and the atmospheric pressure ion source can effectively make up the defect that the atmospheric pressure ionization technology is used for mass spectrum qualitative analysis, and the application prospect is extremely wide.
The present embodiment may also make the following evolution:
1) the sample introducing device 3 can be replaced by any one of tweezers, a sample rod, a glass capillary tube, an ultrasonic atomization sheet, an atomizer, a sampling probe and a spray needle without voltage, and the rest conditions are unchanged;
2) the plasma 5 can be replaced by flame 10, the temperature of the flame 10 can be any value within the range of 400-800 ℃, and the rest conditions are unchanged;
3) the input voltage in the voltage input module 7 can be any value within the range of 15-25 kV, the distance between the two voltage output ends 8 can be any value within the range of 7-10 mm, and other conditions are unchanged;
4) the continuous contact time of the sample and the plasma can be any value within the range of 1-3 minutes, and the rest conditions are unchanged.
Example 3
The device for mass spectrum source internal dissociation based on the plasma principle and the mass spectrometer (the mass analyzer is a triple quadrupole) are adopted for the two psychoactive substances of methamphetamine
And amphetamines
(MW 149, isomers with each other) mass spectrometry was performed:
the sample introduction device 3 is a glass capillary; the plasma 5 is an arc;
preparing methamphetamine and amphetamine into sample solutions of 20 mu g/mL respectively by using a methanol solvent; introducing a sample by dipping in a glass capillary; the voltage input module 7 of the arc discharge device is opened, an arc 6 is generated between the two voltage output ends 8, the input voltage in the voltage input module 7 is 18kV, the distance between the two voltage output ends 8 is 8mm, a sample is continuously contacted with the arc 6 for 1.5 minutes, the sample is dissociated under the actions of heat, energy, chemical reactivity and the like of the arc 6 to generate fragment ions, the fragment ions enter the mass spectrometer through the mass spectrum sample inlet to realize detection, and the mass analyzer is always in an acquisition state.
The same two samples were also subjected to [ M + H ] on a commercial ESI ion source]+Tandem mass spectrometry.
FIG. 11 is [ M + H ] of methamphetamine]+ESI-CID series mass spectrum of (A); FIG. 12 is [ M + H ] of amphetamine]+ESI-CID series mass spectrum of (A); comparing fig. 11 and fig. 12, it can be seen that there is no significant difference between them, i.e. the structural difference between the two isomers is difficult to identify by the fragment information presented by ESI-CID;
FIG. 13 is a mass spectrum of a dissociation of methamphetamine by the mass spectrometric device in source of the invention; FIG. 14 is a mass spectrum of amphetamine dissociation obtained by the mass spectrometer intra-source dissociation apparatus of the present invention; both FIG. 13 and FIG. 14 show the simultaneous presence of charge, free radicals, and fragment ions generated by plasma chemistry-induced fragmentation of a compound (the mass numbers indicated by the circles are those matching the EI spectrum of the compound, and the mass numbers indicated by the diamonds are those matching the [ M + H ] spectrum of the compound]+Fragment ions matched with the ESI-CID mass spectrogram, and additionally labeled with a pentagram, the mass number of the fragment ions is the fragment ions specific to the device), fragment information is very rich, ions with the mass-to-charge ratio of 58 in FIG. 13 and ions with the mass-to-charge ratio of 136 in FIG. 14 become respective characteristic ions, so that two isomers can be well distinguished from the structure, and a new method and a new thought are introduced for qualitative analysis of compounds.
Example 4
The device for mass spectrum source internal dissociation based on the plasma principle and the mass spectrometer (the mass analyzer is a triple quadrupole) for methyl salicylate
And 3-methyl salicylic acid
(MW 152, isomers with each other) mass spectrometry was performed:
the sample introduction device 3 is a glass capillary; the plasma 5 is an arc;
respectively preparing methyl salicylate and 3-methyl salicylic acid into 20 mug/mL sample solutions to be detected by using a methanol solvent; introducing a sample by dipping in a glass capillary; the voltage input module 7 of the arc discharge device is opened, an arc 6 is generated between the two voltage output ends 8, the input voltage in the voltage input module 7 is 15kV, the distance between the two voltage output ends 8 is 8mm, a sample is continuously contacted with the arc 6 for 1.5 minutes, the sample is dissociated under the actions of heat, energy, chemical reactivity and the like of the arc 6 to generate fragment ions, the fragment ions enter the mass spectrometer through the mass spectrum sample inlet to realize detection, and the mass analyzer is always in an acquisition state.
The same two samples were also subjected to [ M + H ] on a commercial ESI ion source]+Tandem mass spectrometry.
FIG. 15 is [ M + H ] of methyl salicylate]+ESI-CID series mass spectrum of (A); FIG. 16 is [ M + H ] of 3-methylsalicylic acid]+ESI-CID series mass spectrum of (A); from fig. 15 and fig. 16, it can be seen that the two isomers have no difference, and only generate the daughter ion with the mass-to-charge ratio of 121, i.e. the structural difference of the two isomers cannot be identified by the fragment information presented by ESI-CID;
FIG. 17 is a mass spectrum of methyl salicylate obtained by the mass spectrometer in-source dissociation device of the present invention; FIG. 18 is a mass spectrum of 3-methylsalicylic acid obtained by the mass spectrometer in-source dissociation device of the present invention; in both FIG. 17 and FIG. 18, there are simultaneously present charge, free radicals and fragment ions generated by dissociation of the plasma-chemically-induced compound (the mass numbers marked with circles are those matching those in the EI spectrum of the compound, and the mass numbers marked with diamonds are those [ M + H ] of the compound]+Fragment ions matched with the ESI-CID mass spectrum, and additionally labeled with a pentagram, the mass number of which is the fragment ions specific to the ion source), the fragment information is very rich, and the ions with the mass-to-charge ratios of 92 and 138 in FIG. 17 and the daughter ions with the mass-to-charge ratios of 93 and 134 in FIG. 18 become the respective characteristic ions of the two isomers, so that the two isomers can be well distinguished from the structure, and the device has excellent performance in qualitative identification of the compound.
It is finally necessary to point out here: the above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.
Claims (10)
1. A mass spectrum source internal dissociation method based on a plasma principle is characterized in that: the ionized or unionized sample is continuously contacted with the plasma for 1-3 minutes to dissociate the sample.
2. The method of claim 1, wherein the method comprises: the temperature of the plasma is 400-800 ℃.
3. The method of claim 1, wherein the method comprises: the plasma is an arc or flame.
4. The method of claim 1, wherein the method comprises: the ionized sample is a sample obtained by ionization treatment through an atmospheric pressure ionization technology.
5. A mass spectrum source internal dissociation device based on a plasma principle is characterized in that: the device comprises a plasma generating device, a mass spectrum sample inlet and a sample introducing device for introducing ionized or unionized samples, wherein the plasma generating device is positioned in front of the mass spectrum sample inlet, and the outlet end or the loaded sample end of the sample introducing device is positioned near the plasma generating device.
6. The plasma-principles-based mass spectrometry intra-source dissociation device of claim 5, wherein: the plasma generating device is an arc discharge device or a flame generating device.
7. The plasma-principles-based mass spectrometry intra-source dissociation device of claim 6, wherein: the arc discharge device comprises a voltage input module and two voltage output ends, wherein a wire is connected between the voltage input module 7 and the voltage output ends, the input voltage of the voltage input module is 15-25 kV, and the distance between the two voltage output ends is 7-10 mm.
8. The plasma-principles-based mass spectrometry intra-source dissociation device of claim 5, wherein: when the sample introduced by the sample introduction device is an ionized sample, the sample introduction device is an atmospheric pressure ionization device, and an outlet end of the ionized sample of the atmospheric pressure ionization device is located in the vicinity of the plasma generation device.
9. The plasma-principles-based mass spectrometry intra-source dissociation device of claim 5, wherein: when the sample introduced by the sample introduction device is an unionized sample, the sample introduction device is a direct sampling device including, but not limited to, forceps, a sample rod, a capillary, an ultrasonic atomization plate, an atomizer, a sampling probe, a needle without a voltage applied.
10. The plasma-principles-based mass spectrometry intra-source dissociation device of claim 5, wherein: the distance between a plasma area generated by the plasma generating device and the mass spectrum sample inlet is 5-15 mm.
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