CN104966657B - Sample introduction interface device for ionization source, mass spectrometry and liquid phase gas chromatograph-mass spectrometer - Google Patents

Abstract

The invention provides a sample introduction interface device for an ionization source, a mass spectrometry and a liquid phase gas chromatograph-mass spectrometer. The sample introduction interface device for the ionization source includes a liquid phase capillary, a gas-liquid spraying pipe, a sheath gas pipeline, a sheath liquid pipeline and a heating component; the liquid phase capillary is provided with a liquid phase inlet; the gas-liquid spraying pipe can convert a liquid sample at the liquid phase outlet of the liquid phase capillary into mist spray and transmit the mist spray to an ionization zone between the outlet of an ion source and the ion sampling opening of the mass spectrometry; the gas-liquid spraying pipe sleeves the liquid phase capillary, so that the gas-liquid spraying pipe and the liquid phase capillary can form a gas-liquid channel; the gas-liquid spraying pipe is provided with a sheath gas inlet and a sheath liquid inlet; the sheath gas pipeline is used for transmitting sheath gas of preset pressure into the gas-liquid channel; the sheath gas pipeline is communicated with the sheath gas inlet; the sheath liquid pipeline is used for transmitting sheath liquid into the gas-liquid channel and is communicated with the sheath liquid inlet; and the heating component is used for heating the mist spray sprayed from the spraying opening of the gas-liquid spraying pipe and is located at one side of the spraying opening of the gas-liquid spraying pipe, wherein the one side of the spraying opening of the gas-liquid spraying pipe is adjacent to the ionization zone. With the sample introduction interface device for the ionization source, the mass spectrometry and the liquid phase gas chromatograph-mass spectrometer of the invention adopted, the influence of inorganic salt and weak-polar organic solvent on the ionization of the mass spectrometer can be decreased, and the application range of the liquid chromatographic-mass spectrometric method can be expanded.

Description

Sampling interface device for ionization source, mass spectrometer and liquid chromatography-mass spectrometer

technical field

The present invention relates to the technical field of detection and analysis, and more specifically, to a sample injection interface device for ionization sources. Liquid Chromatography Mass Spectrometry.

Background technique

Mass spectrometry is a technology that ionizes target molecules through physical and chemical means, and uses electromagnetic fields to distinguish and detect charged molecules according to their mass-to-charge ratios. This technology has the characteristics of fast analysis speed, high sensitivity and strong specificity, so it is widely used in the fields of chemistry and chemical engineering, biology and life science, medicine, pharmacy, material science, environmental protection science and so on. Liquid chromatography analysis technology, including capillary electrophoresis, is a relatively mature separation method, which has the characteristics of high separation efficiency, high sensitivity, fast speed, wide adaptability, good repeatability and convenient operation, so it is widely used in clinical diagnosis of medicine , drug quality control, drug metabolite analysis and pharmacokinetic research and other fields. In recent years, the successful combination of high performance liquid chromatography and mass spectrometry has realized the combination of the strong separation ability of liquid chromatography and the high sensitivity and strong identification ability of mass spectrometry, and can directly separate and analyze samples with complex components.

The existing LC-ESI/MS (liquid chromatography-mass spectrometry) uses an electrospray ionization source (ESI) to ionize the liquid sample separated by liquid chromatography in the capillary and introduce it into the ion transmission channel of the mass spectrometer for detection. However, when the liquid sample contains non-volatile inorganic salts (such as inorganic buffer salts or hydrochloride, etc.), the salts will accumulate at the nozzle, destroy the integrity of the spray, and block the ion transmission channel of the mass spectrometer, and the salt and Weakly polar organic reagents in liquid samples can also produce inhibitory effects such as competitive ionization and matrix effects, which prevent effective ionization of target molecules. Therefore, the scope of application of LC-MS is limited.

To sum up, how to reduce the impact of inorganic salts and weakly polar organic solvents on the ionization of mass spectrometers, so as to expand the application range of liquid chromatography-mass spectrometry, is currently a technical problem to be solved urgently by those skilled in the art.

Contents of the invention

In view of this, the object of the present invention is to provide a sample injection interface device for an ionization source to reduce the impact of inorganic salts and weakly polar organic solvents on the ionization of mass spectrometers, thereby expanding the application range of liquid chromatography-mass spectrometry.

Another object of the present invention is to provide a mass spectrometer with the above-mentioned sample injection interface device for the ionization source and a liquid chromatography-mass spectrometer with the above-mentioned mass spectrometer.

In order to achieve the above object, the present invention provides the following technical solutions:

A sample injection interface device for an ionization source, comprising:

a liquid-phase capillary, the liquid-phase capillary having a liquid-phase inlet for entering a liquid sample;

The liquid sample at the liquid phase outlet of the liquid phase capillary can be converted into a gas-liquid nozzle that is sprayed and transported to the ionization area between the outlet of the ion source and the ion sampling port of the mass spectrometer, and the gas-liquid nozzle is placed outside the A gas-liquid channel is formed between the liquid-phase capillary and the liquid-phase capillary, and a sheath gas inlet and a sheath liquid inlet are arranged on the gas-liquid nozzle;

A sheath gas pipeline for delivering sheath gas of preset pressure into the gas-liquid channel, the sheath gas pipeline communicated with the sheath gas inlet;

a sheath fluid pipeline for delivering sheath fluid into the gas-liquid channel, and the sheath fluid pipeline communicates with the sheath fluid inlet;

A heating element for heating the spray sprayed from the outlet of the gas-liquid nozzle, and the heating element is located on a side of the outlet of the gas-liquid nozzle that is close to the ionization region.

Preferably, in the above-mentioned sample injection interface device for the ionization source, the liquid phase outlet of the liquid phase capillary protrudes from the ejection port of the gas-liquid nozzle.

Preferably, in the above-mentioned sampling interface device for the ionization source, the outlet end of the gas-liquid nozzle tapers from the end far away from the ionization region to the end close to the ionization region, and the nozzle of the gas-liquid nozzle The outlet diameter is 0.8mm-1.2mm;

The distance between the liquid phase outlet of the liquid phase capillary and the discharge port of the gas-liquid nozzle is 0.3mm-0.5mm.

Preferably, in the above-mentioned sampling interface device for the ionization source, the outlet end of the gas-liquid nozzle is a conical outlet, and the conical outlet is detachably connected to the straight pipe section of the gas-liquid nozzle.

Preferably, in the above-mentioned sample injection interface device for the ionization source, the heating element is a cylindrical sleeve that covers the gas-liquid nozzle, and the side of the cylindrical sleeve close to the ionization region has a heating portion;

The sample injection interface device for the ionization source also includes a base, the cylindrical sleeve is arranged on the base and is fixedly connected with the gas-liquid nozzle through bolts, and the cylindrical sleeve is provided with holes for the bolts to pass through. The outer wall of the gas-liquid nozzle is against the bolt, and the outer wall of the gas-liquid nozzle has a plurality of fixed marking lines arranged along its axial direction.

Preferably, in the above-mentioned sample injection interface device for the ionization source, the cylindrical sleeve is arranged on the base through the first micrometer, the second micrometer and the third micrometer, and the first micrometer The micrometer screw of the second micrometer is arranged along the X direction, the micrometer screw of the second micrometer is arranged along the Y direction, the micrometer screw of the third micrometer is arranged along the Z direction, and the frame of the second micrometer fixed on the micrometer screw of the first micrometer, the frame of the third micrometer is fixed on the micrometer screw of the second micrometer, and the cylindrical sleeve is fixedly arranged on the first micrometer On the micrometer screw of the three-micrometer; wherein, the X direction, the Y direction, and the Z direction are perpendicular to each other.

Preferably, in the above-mentioned sample injection interface device for the ionization source, the cylindrical sleeve is further provided with a ceramic cylinder, and the end of the ceramic cylinder away from the ionization zone is connected with the cylinder sleeve away from the ionization zone. One end of the threaded connection.

Preferably, in the above-mentioned sample injection interface device for the ionization source, it also includes:

A control box for controlling the operating voltage and temperature of the heating element;

A diaphragm valve for adjusting the pressure of the sheath gas delivered by the sheath gas pipeline to the gas-liquid nozzle, and the diaphragm valve is arranged on the sheath gas pipeline.

It can be seen from the above-mentioned technical scheme that the sampling interface device for ionization source provided by the present invention includes a liquid phase capillary, a gas-liquid nozzle, a sheath gas pipeline, a sheath liquid pipeline and a heating element; wherein, the liquid phase capillary has a The liquid phase inlet where the sample enters; the gas-liquid nozzle can convert the liquid sample at the liquid phase outlet of the liquid phase capillary into a spray and transport it to the ionization area between the outlet of the ion source and the ion sampling port of the mass spectrometer, the gas-liquid nozzle The sheath gas inlet and the sheath liquid inlet are provided on the gas-liquid nozzle; the sheath gas pipeline is used to deliver sheath gas with preset pressure into the gas-liquid channel. The sheath gas pipeline is connected with the sheath gas inlet; the sheath liquid pipeline is used to transport the sheath liquid into the gas-liquid channel, and the sheath liquid pipeline is connected with the sheath liquid inlet; The spray is heated, and the heating element is located on the side of the gas-liquid nozzle near the ionization area.

In application, the liquid sample is first introduced into the liquid phase capillary from the liquid phase inlet; at the same time, the sheath gas is delivered to the gas-liquid channel through the sheath gas pipeline, and the sheath liquid is delivered to the gas-liquid channel through the sheath liquid pipeline, so that the gas-liquid channel is filled with the pre- The gas-liquid mixed fluid with the pressure (generally 5kPa to 10kPa) can drive the liquid sample flowing out of the liquid phase outlet of the liquid phase capillary to be converted into spray together during the process of the gas-liquid mixed fluid flowing out to the ejection port; The spray is heated, so that the gas-liquid mixture emitted from the ejection port can be fully heated, and then the analyte molecules are vaporized, and the inorganic salt molecules are clustered into solid crystallites, so that the analyte molecules and the analyte molecules in the liquid sample can be effectively separated. Inorganic salts, such as phosphate, carbonate, borate, hydrochloride, etc.; inject the analyte molecules into the ionization zone between the outlet of the ion source and the ion sampling port of the mass spectrometer, and volatilize during this process Protonated solvents such as water and methanol can improve the ionization efficiency of the ionization source, while weakly polar organic solvents are difficult to combine with protons to form quasi-molecular ions, and hardly compete with the analyte for ionization.

In summary, the sample injection interface device for ionization source of the present invention can reduce the influence of inorganic salts and weakly polar organic solvents on the ionization of mass spectrometers, thereby expanding the application range of liquid chromatography-mass spectrometry.

The present invention also provides a mass spectrometer, including a mass spectrometry ion source and a mass spectrometer analyzer, the mass spectrometry ion source is a DART ionization source, and the mass spectrometer also includes a sample injection device for delivering a liquid sample to the DART ionization source The interface device, the sample injection interface device is any one of the above-mentioned sample injection interface devices for the ionization source, because the above-mentioned sample injection interface device for the ionization source has the above-mentioned effect, the mass spectrometer with the above-mentioned sample injection interface device for the ionization source has the same effect, so it will not be repeated in this paper.

The present invention also provides a liquid chromatography-mass spectrometer, comprising a chromatograph and a mass spectrometer connected to the liquid sample outlet of the chromatograph, and the mass spectrometer is any of the above-mentioned mass spectrometers, because the above-mentioned mass spectrometer has For the above effects, the liquid chromatography-mass spectrometer with the above mass spectrometer has the same effect, so it will not be repeated here.

Description of drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are For some embodiments of the present invention, those skilled in the art can also obtain other drawings based on these drawings without creative work.

Fig. 1 is a partial structural schematic diagram of a sample injection interface device for an ionization source provided by an embodiment of the present invention;

Fig. 2 is a schematic diagram of another partial structure of the sample injection interface device for the ionization source provided by the embodiment of the present invention.

detailed description

An embodiment of the present invention provides a sample injection interface device for an ionization source, which can reduce the influence of inorganic salts and weakly polar organic solvents on the ionization of a mass spectrometer, thereby expanding the application range of liquid chromatography-mass spectrometry.

In order to make the purpose, 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 in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments It is a part of embodiments of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

Please refer to the accompanying drawings 1-2, the sample injection interface device for the ionization source provided by the embodiment of the present invention includes a liquid phase capillary 1, a gas-liquid nozzle 2, a sheath gas pipeline 4, a sheath liquid pipeline 5 and a heating element; wherein, the liquid phase The phase capillary 1 has a liquid phase inlet for the liquid sample to enter; the gas-liquid nozzle 2 can convert the liquid sample at the liquid phase outlet of the liquid phase capillary 1 into a spray and transport it to the outlet of the ion source and the ion sampling port of the mass spectrometer The gas-liquid nozzle 2 is covered with the liquid-phase capillary 1 and forms a gas-liquid channel with the liquid-phase capillary 1. The gas-liquid nozzle 2 is provided with a sheath gas inlet and a sheath liquid inlet; the sheath gas pipeline 4 is used for The sheath gas with preset pressure is delivered to the gas-liquid channel, and the sheath gas pipeline 4 is connected to the sheath gas inlet; the sheath fluid pipeline 5 is used to deliver the sheath fluid into the gas-liquid channel, and the sheath fluid pipeline 5 is connected to the sheath fluid inlet; The heating element is used to heat the spray sprayed from the outlet of the gas-liquid nozzle 2, and the heating element is located on the side of the outlet of the gas-liquid nozzle 2 close to the ionization area.

It should be noted that the sheath gas delivered by the sheath gas pipeline 4 to the gas-liquid channel flows along the axial direction of the liquid-phase capillary 1, and together with the sheath liquid drives the liquid sample flowing out of the liquid-phase capillary 1 to spray evenly and continuously. Specifically, in order to reduce the influence of gravity, the gas-liquid nozzle 2 is arranged vertically, the outlet of the ion source and the ion sampling port of the mass spectrometer are located on the same horizontal line, an ionization zone is formed between the two, and the gas-liquid nozzle 2 is arranged Above the ionization area; the heating element is located on the side of the outlet of the gas-liquid nozzle 2 close to the ionization area, that is, the heating element is located directly below the outlet of the gas-liquid nozzle 2, heating the entire spray, and has a better signal effect .

The above-mentioned liquid sample may be a liquid sample directly injected into a liquid sample or a liquid sample separated by chromatography.

In application, the liquid sample is first introduced into the liquid phase capillary 1 from the liquid phase inlet; at the same time, the sheath gas is delivered to the gas-liquid channel through the sheath gas pipeline 4, and the sheath liquid is delivered to the gas-liquid channel through the sheath liquid pipeline 5, so that the gas The liquid channel is filled with a gas-liquid mixed fluid with a preset pressure (generally 5kPa to 10kPa), and when the gas-liquid mixed fluid flows out to the ejection port, it can drive the liquid sample flowing out of the liquid phase outlet of the liquid phase capillary 1 to be converted into a spray together. ;Then the heating element heats the entire spray, so that the gas-liquid mixture emitted from the ejection port can be fully heated, and then the molecules of the analyte are vaporized, and the inorganic salt molecules cluster into solid crystallites, so that the liquid samples can be effectively separated. The analyte molecules and inorganic salts, such as phosphate, carbonate, borate, hydrochloride, etc.; inject the analyte molecules into the ionization area between the outlet of the ion source and the ion sampling port of the mass spectrometer In this process, the volatilized solvents such as water, methanol and other protonated solvents can improve the ionization efficiency of the ionization source, while weakly polar organic solvents are difficult to combine with protons to form quasi-molecular ions, and hardly compete with the analyte for ionization.

In summary, the sample injection interface device for ionization source of the present invention can reduce the influence of inorganic salts and weakly polar organic solvents on the ionization of mass spectrometers, thereby expanding the application range of liquid chromatography-mass spectrometry.

In a specific embodiment, the ionization source of the present invention uses a sample injection interface device to inject the analyte molecules separated by gasification to the outlet of the DART (Direct Analysis in Real Time, real-time direct analysis) ionization source and mass spectrometer In the ionization area between the ion sampling ports, it is introduced into the mass spectrometer after ionization by DART, which is suitable for direct injection of liquid samples and mass spectrometry detection of liquid samples separated by chromatography.

In order to achieve a better spray effect, in the sample injection interface device for the ionization source provided in the above embodiment, the liquid phase outlet of the liquid phase capillary 1 protrudes from the outlet of the gas-liquid nozzle 2 . At this time, the liquid phase outlet of the liquid phase capillary 1 is located outside the outlet of the gas-liquid nozzle 2, that is, on the side close to the ionization area, so as to drive the liquid sample to form a spray. Certainly, the liquid phase outlet of the above-mentioned liquid phase capillary 1 may also be arranged inside the discharge port of the gas-liquid nozzle 2 .

Further, as shown in Figure 1-2, the outlet end of the gas-liquid nozzle 2 tapers from the end away from the ionization source to the end close to the ionization source, and the diameter of the outlet of the gas-liquid nozzle 2 is 0.8mm-1.2mm , preferably 1 mm; the distance between the liquid phase outlet of the liquid phase capillary 1 and the outlet of the gas-liquid nozzle 2 is 0.3 mm-0.5 mm, preferably 0.5 mm. In this way, the gas-liquid nozzle 2 has a smaller ejection port, which speeds up the flow velocity of the sheath liquid sheath gas mixed fluid at the ejection port, and cooperates with the sheath gas and sheath liquid in the gas-liquid channel to drive the liquid sample at the liquid phase outlet. A good gas-liquid blending spray state is obtained, so that there is a better separation effect between the analyte molecules and the inorganic salts. At the same time, the above-mentioned narrowed ejection opening can also limit the swing of the liquid-phase capillary 1 to a certain extent. It can be understood that the above-mentioned gas-liquid nozzle 2 can also be in the shape of a straight cylinder, as long as it can realize the shape that can drive the liquid sample to reach the spray state.

In order to optimize the above technical solution, the outlet end of the gas-liquid nozzle 2 is a conical nozzle, and the conical nozzle is detachably connected to the straight pipe section of the gas-liquid nozzle 2 . At this time, the surface of the gas-liquid nozzle 2 is a conical surface, which is convenient for processing. Specifically, the tapered ejection port is detachable by thread connection, and when the tapered ejection port wears seriously, only the ejection port can be replaced, which saves cost and facilitates disassembly and assembly. The outlet end of the gas-liquid spray pipe 2 can also be a tapered shape formed by a plurality of planes or curved surfaces

In order to make the spray evenly heated, preferably, the heating element is a cylindrical sleeve 3 that is overcoated on the gas-liquid nozzle 2, and the side of the cylindrical sleeve 3 near the ionization region has a heating portion 31; in order to reduce the influence of gravity, the gas-liquid nozzle 2 Arranged along the vertical direction, the outlet of the DART and the ion sampling port of the mass spectrometer of the mass spectrometer are located on the same horizontal line, an ionization zone is formed between the two, the gas-liquid nozzle 2 is arranged above the ionization zone, and the top of the cylindrical sleeve 3 is covered with It is arranged on the outside of the gas-liquid nozzle 2, and the bottom is provided with a heating part 31, which is located under the gas-liquid nozzle 2 to heat the entire spray, and the signal effect is better. Alternatively, the above-mentioned heating element may also be a plurality of heating plates arranged along the circumferential direction.

In order to facilitate installation, the sample injection interface device for the ionization source also includes a base (not shown in the figure), the cylindrical sleeve 3 is arranged on the base and is fixedly connected with the gas-liquid nozzle 2 by bolts, and the cylindrical sleeve 3 is provided with a The threaded through hole through which the bolt passes, the outer wall of the gas-liquid nozzle 2 is against the bolt, and the outer wall of the gas-liquid nozzle 2 has a plurality of fixed marking lines arranged along its axial direction. In the present invention, the bolts pass through the threaded through holes on the cylindrical sleeve 3 and abut against the outer wall of the gas-liquid nozzle 2, and the bolts are used to compress the outer wall of the gas-liquid nozzle 2 to produce slight metal deformation to tighten the cylindrical sleeve 3 and the gas-liquid. Nozzle 2. According to the difference of detecting liquid samples, the present invention also adjusts the height position of the gas-liquid nozzle 2 so that the bolts are locked at the position of the corresponding fixed indication line of the gas-liquid nozzle 2, thereby by changing the height of the gas-liquid nozzle 2, The relative position between the heating part 31 and the ejection port of the gas-liquid nozzle 2 can be adjusted, so that the liquid sample can achieve a better separation state through adjustment, and the ionization effect can be improved. Of course, the cylindrical sleeve 3 and the gas-liquid nozzle 2 can also be fixedly connected through other structures, such as connecting columns respectively welded to the two.

In order to further optimize the above-mentioned technical scheme, the above-mentioned cylindrical sleeve 3 is arranged on the base through the first micrometer, the second micrometer and the third micrometer, the micrometer screw rod of the first micrometer is arranged along the X direction, and the second The micrometer screw of the second micrometer is arranged along the Y direction, the micrometer screw of the third micrometer is arranged along the Z direction, the frame of the second micrometer is fixed on the micrometer screw of the first micrometer, and the micrometer screw of the third micrometer is arranged along the Z direction. The frame of the ruler is fixed on the micrometer screw of the second micrometer, and the cylindrical sleeve 3 is fixedly arranged on the micrometer screw of the third micrometer; wherein, the X direction, the Y direction, and the Z direction are perpendicular to each other. The present invention enables the cylindrical sleeve 3 to be three-dimensionally adjustable relative to the base through three micrometers, so that when analyzing different buffer salt systems and different organic solvent systems, the mass spectrometry of the DART and mass spectrometer can be adjusted by adjusting the ejection port of the gas-liquid nozzle 2 Three-dimensional position of the analyzer to obtain a stable detection signal.

The sampling interface device for ionization source can be integrated with high performance/ultra high performance liquid chromatography/capillary electrophoresis-DART ionization source-mass spectrometer to perform open atmospheric pressure ionization on samples that have undergone liquid phase separation or directly injected liquid samples And the introduction of mass spectrometry for analysis and detection, the device improves the requirements of liquid phase buffer salt for liquid phase chromatography, and strengthens the signal strength and stability of DART detection.

Of course, the present invention can also realize the three-dimensional adjustment of the cylindrical sleeve 3 relative to the base through other devices, such as the X-direction, Y-direction and Z-direction motion mechanism composed of linear slide rails, ball screws and servo motors.

The cylindrical sleeve 3 is also covered with a ceramic cylinder (not shown in the figure), and the end of the ceramic cylinder away from the ionization zone is screwed to the end of the cylinder sleeve 3 away from the ionization zone. The above-mentioned ceramic cylinder can keep the heating part 31 warm, realize heat collection and restrict air flow, and achieve a better separation effect for liquid samples.

Preferably, the sampling interface device for the ionization source also includes a control box for controlling the operating voltage and temperature of the heating element; a diaphragm valve for regulating the pressure of the sheath gas delivered to the gas-liquid nozzle 2 by the sheath gas pipeline 4, and the diaphragm valve is arranged on the sheath on gas line 4. In the specific working process, the working voltage of the heating element is 24V, and the temperature is controlled by the temperature control meter of the control box. The pressure of the sheath gas flow can be adjusted as needed by a diaphragm valve. When the device analyzes different buffer salt systems and different organic solvent systems, stable detection signals can also be obtained by controlling parameters such as heating temperature and sheath gas flow rate.

In order to facilitate assembly, the liquid-phase capillary 1 is fixed on the top end of the gas-liquid nozzle 2 away from the ionization source through a graphite gasket. The graphite gasket is sleeved and sealed between the liquid-phase capillary 1 and the gas-liquid nozzle 2. The sheath gas inlet and the sheath fluid inlet are located on the side of the graphite gasket near the ionization source. At this time, the relative position of the liquid phase outlet of the liquid phase capillary 1 and the discharge port of the gas-liquid nozzle 2 can be adjusted by adjusting the relative position of the graphite gasket and the liquid phase capillary 1 as required.

Further, the inner diameter of the liquid phase capillary 1 is 75 μm-150 μm. The liquid-phase capillary 1 is a metal capillary or a quartz capillary with a polyimide coating on the surface, so that the liquid-phase capillary 1 can be bent for easy adjustment of its position, while reducing damage caused by bending during the working process. The above-mentioned polyimide has good high and low temperature resistance, electrical insulation, adhesion, radiation resistance, medium resistance, chemical stability and flame retardancy, which improves the service life of the liquid-phase capillary 1 .

In the present invention, a waste liquid collecting device is arranged under the ionization area to facilitate the collection of the ejected waste liquid.

The embodiment of the present invention also provides a mass spectrometer, including a mass spectrometry ion source and a mass spectrometer analyzer, the mass spectrometry ion source is a DART ionization source, and the mass spectrometer also includes a sampling interface device for transporting a liquid sample to the DART ionization source. The sample interface device is the sample interface device for the ionization source provided by any of the above-mentioned embodiments, which can reduce the impact of inorganic salts and weakly polar organic solvents on the ionization of the mass spectrometer, thereby expanding the application range of liquid chromatography-mass spectrometry; its advantages are It is brought about by the sample injection interface device for the ionization source. For details, please refer to the relevant parts in the above-mentioned embodiments, and details will not be repeated here.

In an embodiment of specific practice:

The parameter setting of the injection interface device for the ionization source: the heating temperature is 250°C, the sheath gas pressure is 5kPa, the DART temperature is 350°C, the distance between the DART and the mass spectrometer is 10mm, and the ejection port is located above the connecting line between the DART and the mass spectrometer. Analyzer 7mm.

The liquid sample to be tested is reserpine with a concentration of 5 μg/mL, dissolved in a water/acetonitrile ratio of 1:1, and the solution system contains 137mM NaCl, 2.7mM KCl, 10mM Na ₂ HPO ₄ , 2mM KH ₂ PO ₄ .

The sample enters the device through a peristaltic pump at a flow rate of 200 μL/min, which eliminates the interference of inorganic salts and obtains a good ionization effect.

In another embodiment of specific practice:

Parameter setting of the sampling interface device for the ionization source: the heating temperature of the device is 260°C, the sheath gas pressure is 10kPa, the DART temperature is 350°C, the distance between the DART and the mass spectrometer is 15mm, and the ejection port is located above the line connecting the DART and the mass spectrometer Mass Spec 10mm.

The samples to be tested were seven benzodiazepines including lorazepam, clonazepam, diazepam, oxazepam, nitrazepam, chlordiazepoxide, and midazolam maleate. After dissolving in medium, dilute with phosphoric acid-potassium dihydrogen phosphate solution at pH 2.5 to a concentration of 30-150 μg/mL.

The mixed sample was separated by gradient elution through liquid chromatography and introduced into the device. The LC-MS spectrum obtained after DART ionization was not significantly different from the separation degree of pure liquid phase separation, and the seven substances could be ionized well. not affected by phosphate.

The DART ionization source adopted in the present invention has good tolerance to inorganic salts, non-protonated solvents and weakly polar solvents. DART (Direct Analysis Technology in Real Time) ionization source is a new type of open atmospheric pressure ionization technology. DART technology is developed based on the principle of atmospheric pressure chemical ionization (APCI). Ionization through this molecular-ion reaction can ionize target molecules when the sample contains high salt and strong matrix effect. Its main ionization process mainly includes the reaction of excited state gas (such as nitrogen, helium or argon) atoms generated by the discharge with the water in the ambient air, through the formation of water molecule clusters.

There are two principles of ionization, that is, the method of ionization in which the molecules further react with the sample molecules to generate quasi-molecular ions of the analyte, and the method of ionization in which the excited state gas atoms directly react with the molecules of the analyte in the gas phase to generate molecular ions, that is, Penningionization.

Solvents volatilized during this process, such as water, methanol and other protonated solvents, can improve the ionization efficiency of DART. The LC-MS spectrum obtained after DART ionization has no significant difference from the resolution of pure liquid phase separation, and all seven substances can be well ionized without being affected by phosphate.

The embodiment of the present invention also provides a liquid chromatography-mass spectrometer, including a chromatograph and a mass spectrometer connected to the liquid sample outlet of the chromatograph, the mass spectrometer is the above-mentioned mass spectrometer, because the above-mentioned mass spectrometer has the above-mentioned effects, it has the above-mentioned The liquid chromatography-mass spectrometer of the mass spectrometer has the same effect, so it will not be repeated here.

The invention realizes the combined analysis of liquid chromatography and DART-MS. And by optimizing the position of the liquid phase effluent and the entrance of the mass spectrometer, the type of auxiliary solvent, and various parameters related to ionization, the qualitative and quantitative analysis of compounds with different properties can be realized. LC-DART-MS analysis method of samples. The invention will greatly expand the application of DART in related fields, and further relax the requirement of liquid phase buffer salt for liquid-mass coupling.

Each embodiment in this specification is described in a progressive manner, each embodiment focuses on the difference from other embodiments, and the same and similar parts of each embodiment can be referred to each other.

The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention will not be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (8)

1. a kind of ionization source sample introduction interface arrangement, it is characterised in that include：

Liquid phase capillary tube (1), the liquid phase capillary tube (1) is with the fluid inlet entered for liquid sample；

Can by the liquid sample of the liquid-phase outlet of the liquid phase capillary tube (1) be converted into spraying be transported to it is ionogenic outlet with The gas-liquid jet pipe (2) of the ionized region between the ion thief hatch of mass analyzer, the gas-liquid jet pipe (2) are coated at the liquid phase Capillary tube (1) simultaneously forms gas-liquid channel between the liquid phase capillary tube (1), is provided with sheath gas and enters on the gas-liquid jet pipe (2) Mouth and sheath fluid import；

For into the gas-liquid channel convey preset pressure sheath gas sheath air pipe (4), the sheath air pipe (4) with it is described Sheath gas inlet communication；

For the sheath liquid pipeline (5) for conveying sheath fluid into the gas-liquid channel, the sheath liquid pipeline (5) is connected with the sheath fluid import It is logical；

For the heating member heated to the spraying that the ejiction opening from the gas-liquid jet pipe (2) sprays, the heating member is located at The ejiction opening of the gas-liquid jet pipe (2) is near the side of the ionized region；

The heating member is to be coated at the cylindrical sleeves (3) of the gas-liquid jet pipe (2), the cylindrical sleeves (3) near it is described from The side of component has heating part (31)；

Ionization source sample introduction interface arrangement also includes base, and the cylindrical sleeves (3) are arranged on the base and pass through Bolt is fixedly connected with the gas-liquid jet pipe (2), is provided with and leads to for the screw thread that the bolt is passed through on the cylindrical sleeves (3) Hole, the outer wall of the gas-liquid jet pipe (2) are offseted with the bolt, and with setting along its axial direction on the gas-liquid jet pipe (2) outer wall The a plurality of fixed marking line put；

The cylindrical sleeves (3) are arranged on the base by the first micrometer, the second micrometer and the 3rd micrometer, institute The micrometric screw of the first micrometer is stated along X to setting, the micrometric screw of second micrometer is arranged along Y-direction, the described 3000th The micrometric screw of chi is divided to arrange along Z-direction, the framework of second micrometer is fixed on the micrometric screw of first micrometer, The framework of the 3rd micrometer is fixed on the micrometric screw of second micrometer, and the cylindrical sleeves (3) are fixedly installed On the micrometric screw of the 3rd micrometer；Wherein, X is vertical two-by-two to, Y-direction, Z-direction.

2. ionization source as claimed in claim 1 sample introduction interface arrangement, it is characterised in that the liquid of the liquid phase capillary tube (1) Mutually outlet protrudes from the ejiction opening of the gas-liquid jet pipe (2).

3. ionization source as claimed in claim 2 sample introduction interface arrangement, it is characterised in that the outlet of the gas-liquid jet pipe (2) End is from the one end away from the ionized region to the tapered at one end near the ionized region, and the ejiction opening of the gas-liquid jet pipe (2) A diameter of 0.8mm-1.2mm；

The distance of ejiction opening of the liquid-phase outlet of the liquid phase capillary tube (1) away from the gas-liquid jet pipe (2) is 0.3mm-0.5mm.

4. ionization source as claimed in claim 3 sample introduction interface arrangement, it is characterised in that the outlet of the gas-liquid jet pipe (2) Hold as taper ejiction opening, the taper ejiction opening is detachably connected with the straight length of the gas-liquid jet pipe (2).

5. ionization source as claimed in claim 1 sample introduction interface arrangement, it is characterised in that the cylindrical sleeves (3) also cover outward Be provided with ceramic cylinder, the ceramic cylinder away from the ionized region one end with the cylindrical sleeves (3) away from the ionized region Threaded one end connection.

6. ionization source as claimed in claim 1 sample introduction interface arrangement, it is characterised in that also include：

Control the control chamber of the running voltage and temperature of the heating member；

The diaphragm valve of the sheath atmospheric pressure that the sheath air pipe (4) is transported in the gas-liquid jet pipe (2) is adjusted, the diaphragm valve sets Put on the sheath air pipe (4).

7. a kind of mass spectrograph, including mass ion source and mass analyzer, it is characterised in that the mass ion source is that DART is electric From source, the mass spectrograph is also included for liquid sample to be transported to the sample introduction interface arrangement of the DART ionization sources, it is described enter Sample interface arrangement is the ionization source sample introduction interface arrangement as described in any one of claim 1-6.

8. a kind of liquid chromatography mass combined instrument, including chromatograph and the mass spectrum being connected with the chromatographic liquid sample outlet Instrument, it is characterised in that the mass spectrograph is mass spectrograph as claimed in claim 7.