A continuous sample injection ionization device and its application

Abstract

The present invention discloses a continuous injection ionization device and its application, wherein the continuous injection ionization device comprises a continuous injection channel, a heat energy generating device and a mass spectrometry injection channel, the head end of the continuous injection channel is connected to the continuous injection device, the outlet end of the continuous injection channel is located on the axis of the mass spectrometry injection channel, and the heat energy generating device is located around the outlet end of the continuous injection channel. Experiments have shown that the continuous injection ionization device provided by the present invention is not only easy to realize ionization and simple to operate, but also can meet the ionization requirements of compounds of different molecular weights, has low selectivity for samples to be tested, can test a wide range of sample objects, and has strong applicability; in particular, the continuous ionization realized by the present invention can significantly improve the accuracy and reproducibility of mass spectrometry analysis results, and can also realize quantitative analysis and online analysis, with significant practical value.

Description

Technical Field

[0001] The invention relates to a continuous sample injection ionization device and application thereof, belonging to the technical field of mass spectrometry analysis. Background Art

[0002] Mass spectrometry (MS) is a powerful tool for analyzing complex mixtures and providing information about the molecules, weight, and chemical structure of the analytes. In recent years, with the continuous innovation and improvement of ionization technology and mass analyzers, mass spectrometry has become one of the fastest growing analytical technologies. Currently, mass spectrometry technology is increasingly used in chemistry and chemical engineering, biology and life sciences, medicine, pharmacy, materials science, environmental protection and other fields.

[0003] In recent years, atmospheric pressure ionization methods in mass spectrometry have begun to receive widespread attention and research interest. Compared with previous mass spectrometry techniques, atmospheric pressure ionization methods have many advantages, such as: samples can be analyzed under open and atmospheric pressure conditions, irregular samples can be directly analyzed, samples that are easily damaged by vacuum can be analyzed, no complex sample pretreatment is required, and they can be used in conjunction with a variety of mass spectrometers, making it easy to identify and analyze compounds in mixtures. At present, there are dozens of atmospheric pressure ionization methods, which are mainly divided into three categories: one is liquid extraction, such as extraction electrospray ionization (EESI), probe electrospray ionization (PESI), paper spray (PS), etc.; the second is laser desorption, such as electrospray-assisted laser desorption (ELDI), laser ablation electrospray ionization (LAESI), matrix-assisted electrospray ionization (MALDESI), etc.; the third is thermal desorption, such as direct analysis in real time (DART), low temperature plasma (LTP), etc.

[0004] The emergence of DART and DESI has opened up the development of atmospheric pressure open ionization technology. In the past decade, atmospheric pressure ionization technology has experienced explosive growth, but there are not many reports on atmospheric pressure ionization technology that can be connected to a continuous sampling device. Currently, there are reports on the connection of DART and DESI atmospheric pressure ionization technology with liquid chromatography, but some of the connection devices for continuous sampling devices used in conjunction with open ionization technology are very complex, with many adjustment parameters, and usually require high voltages to achieve ionization. Summary of the invention

[0005] In view of the above problems existing in the prior art, the purpose of the present invention is to provide a continuous sampling ionization device and its application which integrates ionization and continuous sampling, does not require assistance such as voltage and laser, and can realize ionization during the continuous sampling process.

[0006] In order to achieve the above-mentioned invention object, the present invention adopts the following technical scheme:

[0007] The continuous injection ionization device described in the present invention comprises a continuous injection channel, a thermal energy generating device and a mass spectrometry injection channel. The head end of the continuous injection channel is connected to the continuous injection device, the outlet end of the continuous injection channel is located on the axis of the mass spectrometry injection channel, and the thermal energy generating device is located around the outlet end of the continuous injection channel.

[0008] As a preferred solution, the distance between the heat energy generating device and the outlet end of the continuous injection channel is 0 to 10 cm.

[0009] As a preferred embodiment, the angle between the central axis of the outlet end of the continuous injection channel and the central axis of the mass spectrometry injection channel is 0 to 90 degrees or 270 to 360 degrees.

[0010] As a preferred solution, the distance between the outlet end of the continuous injection channel and the inlet end of the mass spectrometry injection channel is 1 to 100 mm.

[0011] As a preferred solution, the diameter of the continuous injection channel is 1 μm to 5 cm.

[0012] The continuous injection channel is a pipe made of high temperature resistant material, and the high temperature resistant material includes but is not limited to metal, glass, and quartz material.

[0013] The continuous sampling device includes but is not limited to liquid chromatography, a syringe pump, and capillary electrophoresis. The liquid chromatography includes but is not limited to normal phase liquid chromatography and reverse phase liquid chromatography.

[0014] The heat energy generating device includes but is not limited to an electric heating device or a flame generating device, and the electric heating device includes but is not limited to a hair dryer, an electric air gun, an electric soldering iron or an electric heating wire; the flame generating device includes but is not limited to a fuel storage tank and a delivery pipe.

[0015] The flame is generated by the combustion of inorganic fuel or organic fuel, the inorganic fuel includes but is not limited to hydrogen, the organic fuel includes but is not limited to hydrocarbon fuel, alcohol fuel, ketone fuel, ether fuel or ester fuel, the hydrocarbon fuel includes but is not limited to saturated alkanes, unsaturated alkanes or a mixture of multiple hydrocarbons, preferably propane, n-butane, acetylene, gasoline or diesel.

[0016] The continuous injection ionization device of the present invention can be used for continuous injection, ionization and mass spectrometry analysis of liquid samples or sample solutions. The samples can be polar compounds, non-polar compounds, metal complexes, actual samples, etc., including macromolecular compounds and small molecular compounds. The macromolecular compounds include but are not limited to polypeptides, proteins, etc., and the small molecular compounds include but are not limited to amine substances, steroid compounds, fatty acids, etc.; the sample solution refers to a solution prepared by dissolving the sample with a suitable solvent, and the suitable solvent is a polar solvent, including but not limited to water, ketone solvents, ester solvents, halogenated hydrocarbon solvents, alcohol solvents, etc. The concentration of the sample solution can be 1pg / mL~50mg / mL; the flow rate of continuous injection is not less than 1μL / min, and the temperature for continuous ionization can be 50~1000℃, preferably 300~600℃.

[0017] Compared with the prior art, the present invention has the following significant beneficial effects:

[0018] Experiments have proved that the continuous sample introduction ionization device provided by the present invention is not only easy to realize ionization and simple to operate, but also can meet the ionization requirements of compounds of different molecular weights, has low selectivity for samples to be tested, can test a wide range of sample objects, and has strong applicability; in particular, the continuous ionization realized by the present invention can significantly improve the accuracy and reproducibility of mass spectrometry analysis results, and can also realize quantitative analysis and online analysis, and has significant practical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 A schematic diagram of the structure of a continuous sample injection ionization device provided in an embodiment of the present invention;

[0020] Figure 2 This is the mass spectrometry analysis diagram obtained in Example 1 of the present invention;

[0021] Figure 3 This is the mass spectrum analysis diagram obtained in Example 2 of the present invention;

[0022] Figure 4 This is the mass spectrum analysis diagram obtained in Example 3 of the present invention;

[0023] Figure 5 This is the mass spectrum analysis diagram obtained in Example 3 of the present invention;

[0024] Figure 6 This is the mass spectrometry analysis diagram obtained in Example 4 of the present invention.

[0025] The numbers in the figure are as follows:

[0026] 1. Continuous injection channel; 11. Exit end; 2. Thermal energy generating device; 3. Mass spectrometry injection channel. DETAILED DESCRIPTION

[0027] The technical solution of the present invention is further described in detail and completely below in conjunction with the embodiments and drawings.

[0028] Example 1

[0029] like Figure 1 As shown: A continuous injection ionization device provided by the present invention includes a continuous injection channel 1, a thermal energy generating device 2 and a mass spectrometry injection channel 3, the head end of the continuous injection channel 1 is connected to the continuous injection device (not shown in the figure, including but not limited to liquid chromatography, an injection pump, capillary electrophoresis, the liquid chromatography includes but not limited to normal phase liquid chromatography and reverse liquid chromatography), the outlet end 11 of the continuous injection channel 1 is located on the axis of the mass spectrometry injection channel 3, and the thermal energy generating device 2 is located around the outlet end 11 of the continuous injection channel.

[0030] The continuous injection channel 1 is a pipe with a diameter of 1 μm to 5 cm made of a high temperature resistant material, and the high temperature resistant material includes but is not limited to metal, glass, and quartz material.

[0031] The heat energy generating device 2 includes but is not limited to an electric heating device or a flame generating device, and the electric heating device includes but is not limited to a hair dryer, an electric air gun, an electric soldering iron or an electric heating wire; the flame generating device includes but is not limited to a fuel storage tank and a delivery pipe.

[0032] The flame is generated by the combustion of inorganic fuel or organic fuel, the inorganic fuel includes but is not limited to hydrogen, the organic fuel includes but is not limited to hydrocarbon fuel, alcohol fuel, ketone fuel, ether fuel or ester fuel, the hydrocarbon fuel includes but is not limited to saturated alkanes, unsaturated alkanes or a mixture of multiple hydrocarbons, preferably propane, n-butane, acetylene, gasoline or diesel.

[0033] Will Figure 1 The continuous sample injection ionization device shown is combined with a mass spectrometer (mass analyzer triple quadrupole) for reserpine (Reserpine, MW = 608): Perform mass spectrometry analysis:

[0034] The heat energy is provided by flame, and the continuous sampling device is a syringe pump;

[0035] First, reserpine is dissolved in a mixed solvent of water and acetonitrile (volume ratio is 1:1) to prepare a sample solution with a concentration of 100 μg / mL, and 500 μL of the sample solution is drawn by an injection needle. Then, the injection needle is connected to the head end of the continuous injection channel, and the injection flow rate is controlled to be 100 μL / min by an injection pump. Then, the outlet end 11 of the continuous injection channel is located on the axis of the mass spectrometry injection channel 3 (the angle α between the central axis of the outlet end 11 of the continuous injection channel and the central axis of the mass spectrometry injection channel 3 can be 0 to 90 degrees or 270 to 360 degrees; the distance d between the outlet end 11 of the continuous injection channel and the inlet end of the mass spectrometry injection channel 3 is 1 to 100 mm), and the flame is continuously heated around the outlet end 11 of the continuous injection channel (the heat energy generating device 2 is located within a range of 0 to 10 cm from the outlet end 11 of the continuous injection channel) to a temperature of 300 to 600° C., and the mass analyzer is always in a collection state.

[0036] Figure 2 The mass spectrum obtained is Figure 2 The mass spectrum shown shows that: the ion peak [M+H] related to reserpine appears in the spectrum + =609, indicating that the continuous sample introduction ionization device of the present invention can ionize the reserpine sample well.

[0037] Example 2

[0038] Will Figure 1 The continuous sample inlet ionization device shown is combined with a mass spectrometer (mass analyzer triple quadrupole) to 18-crown-6 (18-crown-6, MW = 264): Perform mass spectrometry analysis:

[0039] The heating wire is used to provide heat energy, and the continuous sampling device is a syringe pump;

[0040] First, 18-crown-6 is dissolved in a mixed solvent of water and acetonitrile (volume ratio of 1:1) to prepare a sample solution with a concentration of 1000 μg / mL, and 500 μL of the sample solution is drawn by an injection needle. Then, the injection needle is connected to the head end of the continuous injection channel, and the injection flow rate is controlled to be 100 μL / min by an injection pump. Then, the outlet end 11 of the continuous injection channel is located on the axis of the mass spectrometry injection channel 3 (the angle α between the central axis of the outlet end 11 of the continuous injection channel and the central axis of the mass spectrometry injection channel 3 can be 0 to 90 degrees or 270 to 360 degrees; the distance d between the outlet end 11 of the continuous injection channel and the inlet end of the mass spectrometry injection channel 3 is 1 to 100 mm), and the heating wire is continuously heated around the outlet end 11 of the continuous injection channel (the heat energy generating device 2 is located within a range of 0 to 10 cm from the outlet end 11 of the continuous injection channel) to a temperature of 300 to 600°C, and the mass analyzer is always in a collection state.

[0041] Figure 3 The mass spectrum obtained is Figure 3 The mass spectrum shown shows that: the ion peak [M+Na] related to 18-crown ether-6 appears in the spectrum + =287 and [M+K] + =303, indicating that the continuous sample introduction ionization device of the present invention can ionize the crown ether samples well.

[0042] Example 3

[0043] Will Figure 1 The continuous sample injection ionization device shown is combined with a mass spectrometer (the mass analyzer is a triple quadrupole) to analyze the pesticide residue Imazalil (MW=297): Perform mass spectrometry analysis:

[0044] The heating wire is used to provide heat energy, and the continuous sampling device is a reverse liquid chromatography;

[0045] First, a mixed solvent of water and acetonitrile (volume ratio of 1:1) is used to dissolve imazalil to prepare a sample solution with a concentration of 230 ng / mL, and the mobile phase is 0.1% trifluoroacetic acid aqueous solution: acetonitrile (15:85, volume ratio), and the flow rate is 0.2 mL / min. Then, the liquid chromatograph is directly connected to the head end of the continuous injection channel, and the outlet end 11 of the continuous injection channel is located on the axis of the mass spectrometry injection channel 3 (the angle α between the central axis of the outlet end 11 of the continuous injection channel and the central axis of the mass spectrometry injection channel 3 can be 0-90 degrees or 270-360 degrees; the distance d between the outlet end 11 of the continuous injection channel and the inlet end of the mass spectrometry injection channel 3 is 1-100 mm), and the heating wire is continuously heated around the outlet end 11 of the continuous injection channel (the heat energy generating device 2 is located within a range of 0-10 cm from the outlet end 11 of the continuous injection channel) to reach a temperature of 300-600° C., and the mass analyzer is always in a collection state.

[0046] Figure 4 This is the mass spectrum of imazalil obtained in scan mode. Figure 5 is the chromatogram of m / z 297 in the mass spectrum obtained in selected ion monitoring (SIM) mode, Figure 5 It can be seen from the chromatogram shown that the chromatographic peak of imazalil appears in the spectrum, indicating that the continuous sample introduction ionization device of the present invention can ionize the pesticide samples well.

[0047] Example 4

[0048] Will Figure 1 The continuous sample inlet ionization device shown is combined with a mass spectrometer (mass analyzer triple quadrupole) to analyze neurotensin acetate (MW=1672): Perform mass spectrometry analysis:

[0049] The heating wire is used to provide heat energy, and the continuous sampling device is a syringe pump;

[0050] First, vasopressin is dissolved in a mixed solvent of water and acetonitrile (volume ratio is 1:1) to prepare a sample solution with a concentration of 100 μg / mL, and 500 μL of the sample solution is drawn by an injection needle. Then, the injection needle is connected to the head end of the continuous injection channel, and the injection flow rate is controlled to be 100 μL / min by an injection pump. Then, the outlet end 11 of the continuous injection channel is located on the axis of the mass spectrometry injection channel 3 (the angle α between the central axis of the outlet end 11 of the continuous injection channel and the central axis of the mass spectrometry injection channel 3 can be 0 to 90 degrees or 270 to 360 degrees; the distance d between the outlet end 11 of the continuous injection channel and the inlet end of the mass spectrometry injection channel 3 is 1 to 100 mm), and the heating wire is continuously heated around the outlet end 11 of the continuous injection channel (the heat energy generating device 2 is located within a range of 0 to 10 cm from the outlet end 11 of the continuous injection channel) to a temperature of 300 to 600° C., and the mass analyzer is always in a collection state.

[0051] Figure 6 The mass spectrum obtained is Figure 6 The mass spectrum shown shows that: the ion peak related to vasopressin [M+2H] 2+ =837, indicating that the continuous sample introduction ionization device of the present invention can achieve good ionization of polypeptide samples.

[0052] From the above experiments, it can be seen that the continuous sampling ionization device described in the present invention can be well connected to a continuous sampling device such as a liquid chromatograph and a syringe pump, and can analyze and separate polar, highly polar, non-polar, metal organic compounds, etc. It not only has a wide range of test sample objects, but also can test samples of different molecular weights, and has significant progress and practicality.

[0053] Finally, it should be noted that the above content is only used to further illustrate the technical solution of the present invention in detail and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by technicians in this field based on the above content of the present invention all fall within the scope of protection of the present invention.

Claims

1. A method for mass spectrometry analysis of the pesticide residue imazalil using a continuous sample introduction ionization device, characterized in that: The continuous injection ionization device comprises a continuous injection channel, a heat energy generating device and a mass spectrometry injection channel, the head end of the continuous injection channel is connected to the continuous injection device, the outlet end of the continuous injection channel is located on the axis of the mass spectrometry injection channel, the heat energy generating device is located around the outlet end of the continuous injection channel, the heat energy generating device is a heating wire, and the continuous injection device is a reverse liquid chromatography; the distance between the heat energy generating device and the outlet end of the continuous injection channel is 0 to 10 cm; the angle between the central axis of the outlet end of the continuous injection channel and the central axis of the mass spectrometry injection channel is 0 to 90 degrees or 270 to 360 degrees; the distance between the outlet end of the continuous injection channel and the inlet end of the mass spectrometry injection channel is 1 to 100 mm; The method comprises the following operations: firstly, dissolving imazalil in a mixed solvent with a volume ratio of water to acetonitrile of 1:1 to prepare a sample solution with a concentration of 230 ng / mL, the mobile phase is a mixed solvent with a volume ratio of 0.1% trifluoroacetic acid aqueous solution and acetonitrile of 15:85, and the flow rate is 0.2 mL / min; then, the liquid chromatograph is directly connected to the head end of a continuous injection channel, and the outlet end of the continuous injection channel is located on the axis of a mass spectrometer injection channel, and a heating wire is continuously heated around the outlet end of the continuous injection channel to make the temperature reach 300-600°C, and the mass analyzer is always in a collection state.

2. The method according to claim 1, characterized in that: The diameter of the continuous injection channel is 1 μm to 5 cm.

3. The method according to claim 2, characterized in that: The continuous injection channel is a pipe made of high temperature resistant material.

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