TWI423296B - A conversion assembly for converting the electrospray free device into an atmospheric pressure chemical free device, and a free device using the conversion assembly - Google Patents

Description

Conversion assembly for converting an electrospray free device to an atmospheric pressure chemical free device and a free device using the same

The invention relates to a conversion component for a liquid chromatography mass spectrometer, in particular to a conversion component for converting an electrospray free device of a liquid chromatography mass spectrometer into an atmospheric pressure chemical free device, and a conversion using the same Free device of the assembly.

Because Liquid Chromatography-Mass Spectrometer (LC/MS) has the advantages of high sensitivity and good selectivity, it has become the most important instrument for analyzing biological samples in recent years, and is widely used in foods such as food. Detection of vitamins, preservatives, pesticides, growth hormones, and harmful additives; drug metabolism analysis of organisms, screening of diseases, and detection of drug content in humans.

Liquid chromatography mass spectrometry (LC/MS) mainly combines Liquid Chromatography (LC) with Mass Spectrometer (MS) and separates the sample to be tested by liquid chromatography. Then use a mass spectrometer for analysis. The mass spectrometer mainly comprises a free device, a mass analyzer and a detector, and the applicable free device is different according to the physical and chemical characteristics of the sample. Generally speaking, when the polarity of the object to be tested is high, An electrospray ionization (ESI) device is generally used; and when the analyte is of medium or low polarity, an atmospheric chemical ionization (APCI) device is often used.

The first figure shows a schematic diagram of the free mechanism of the commercial electrospray free device 10. The electrospray free device 10 has a tip 11, which is provided with a metal capillary 13 and a mist. Nebulizer Gas 60 can be ejected from the nozzle 11; the nozzle end 131 of the metal capillary 13 corresponds to the inlet 53 of the sample cone 51 of the mass analyzer 50, when a high voltage is applied to the head 11 and the mass analyzer 50. When the cone 51 is injected, a potential difference of about 3000 to 5000 volts is formed between the nozzle end 131 of the metal capillary 13 and the inlet 53 of the mass analyzer 50, after which the sample solution 70 to be tested in the metal capillary 13 is subjected to The influence of the electric field force and the surface tension of the liquid forms a Taylor Cone T. When the electric field force is greater than the surface tension of the liquid, an electric spray phenomenon occurs, and the charged micro-droplet 71 is generated as the micro-droplet. After the solvent in 71 is boiled by the atomizing gas 60 and gradually volatilized, the analyte ions 73 are formed, and then enter the mass analyzer 50 through the inlet 53 to finally obtain a mass spectrum.

The second figure shows a schematic diagram of the free mechanism of the commercial atmospheric pressure chemical free device 20. The atmospheric pressure chemical free device 20 has a metal capillary 21 which is passed through a heating jacket 23, metal. The nozzle end 211 of the tube 21 corresponds to the inlet 53 of the mass analyzer 50. When the sample solution 70 to be tested in the metal tube 21 flows out from the nozzle end 211, an atomizing gas 60 disposed coaxially with the metal tube 21 will The sample solution 70 is dispersed, and the heating jacket 23 vaporizes the analyte and solvent in the sample solution 70 into gaseous molecules, and then applies a high voltage to the corona discharge needle 80 through the power supply P for corona. The discharge is such that the analyte and the gaseous molecules of the solvent are released, and then reacted by proton transfer or the like to form the singly charged analyte ion 71, and then enter the mass analyzer 50 to obtain a mass spectrum.

As mentioned above, since the appropriate free device must be selected for the structural characteristics of the analyte during the actual detection process, it is necessary to replace the free device from time to time, which is not only laborious and cumbersome, resulting in a complicated and time-consuming detection process. Inconvenience. In addition, after the discharge needle and the heating sleeve of the commercial atmospheric pressure chemical free device are used for a long time, the discharge needle is easy to deposit carbon, and the ion signal is lowered, and the heating sleeve is also easily dirty, so it is necessary to clean and polish from time to time. The discharge needle is inconvenient to use and difficult to maintain.

In view of the above, it is a primary object of the present invention to provide a conversion assembly that can be directly mounted to a spray head of an electrospray free device to convert an electrospray free device into an atmospheric pressure chemical free device.

Another object of the present invention is to provide a free device using the foregoing conversion assembly, which can not only achieve a detection result similar to that of a commercial atmospheric pressure chemical free device, but also is convenient to use and requires no maintenance.

In order to achieve the foregoing object, a conversion assembly provided by the present invention is mounted on a nozzle of an electrospraying device, and a metal capillary tube protruding from an open end of the nozzle is disposed inside the nozzle, and an atomizing gas is self-contained. The open end of the nozzle is ejected, and the electrospray free device is installed in a mass spectrometer, and the mass spectrometer comprises a mass analyzer having an inlet; the conversion assembly mainly comprises a metal cover disposed outside the nozzle a nozzle end of the metal capillary is located in the metal cover, and an inert metal wire coaxially disposed on the metal cover, one end of which is located on the discharge path of the atomizing gas, and corresponds to the advance of the mass analyzer Sample mouth. Thereby, the conversion assembly of the present invention is capable of successfully converting an electrospray free device into an atmospheric pressure chemical free device.

In the conversion assembly provided by the present invention, the metal cover has an open end, and the open end of the metal cover is spaced apart from the nozzle end of the metal capillary, and the distance between the two is preferably in the range of 2 mm to 4 mm.

Alternatively, the metal cover can be a metal mesh, a metal housing or the like.

In the conversion assembly provided by the present invention, the metal cover further includes a set of cross reeds, the set of reeds being disposed on an inner wall surface of the metal cover, such that the set of reeds can be interposed between the outer wall surface of the shower head and the Between the inner wall surfaces of the metal cover. Thereby, the conversion assembly can be easily and quickly attached to the spray head through the elasticity of the spring itself.

In the conversion assembly provided by the present invention, the inert metal wire may be a metal selected from the group consisting of platinum, rhodium, gold, ruthenium, palladium, iridium, osmium, iridium, alloys of the foregoing metals, and stainless steel; The outer diameter of the inert wire preferably ranges from 100 μm to 150 μm, and more preferably, the platinum wire having an outer diameter of 100 μm is preferably used in the present invention.

In another aspect, the present invention also provides a free device using the foregoing conversion assembly, comprising a shower head having a metal capillary bore therein, a metal cover disposed outside the showerhead, and a coaxial cover disposed on the metal cover. An inert wire; wherein the nozzle has an open end for ejecting an atomizing gas, the metal capillary has a nozzle end protruding from the open end of the nozzle, and is sprayable by a sample solution, and The nozzle end of the metal capillary is located in the metal cover, and one end of the inert wire is located on the discharge path of the atomizing gas and is corresponding to the inlet of the mass analyzer. Thereby, the free device of the present invention can achieve a detection result similar to that of the commercial atmospheric pressure chemical free device.

With regard to the detailed construction of the conversion assembly and the free apparatus provided by the present invention and the features thereof, the embodiments will be exemplified and in conjunction with the drawings, which can be carried out within the scope of the embodiments of the present invention which can be easily implemented by those skilled in the art. Description.

The following is a brief description of the contents of the drawings used in conjunction with the embodiments of the present invention, wherein: FIG. 3 is a perspective view showing a conversion assembly according to a preferred embodiment of the present invention; and FIG. 4 is a cross-sectional view of the third diagram; Figure 5 is a schematic view showing the conversion component of the present invention disposed on the nozzle and the position opposite to the mass analyzer; the sixth figure is a schematic view showing the possible separation of the conversion component of the present invention after being placed on the nozzle 7 is a partial cross-sectional view showing a free device according to another preferred embodiment of the present invention; and FIGS. 8A to C are mass spectra showing the detection result of the experimental example 1 of the present invention in the negative ion mode; Figs. A to C are mass spectra showing the results of detection of the experimental example 2 of the present invention in the positive ion mode; and the tenth diagrams A to C are mass spectra showing the results of the detection of the negative ion mode of the experimental example 2 of the present invention.

The Applicant first describes here that in the embodiments to be described below, the same reference numerals denote the same or similar elements.

Referring to the third to fourth figures, a conversion assembly 30 according to a preferred embodiment of the present invention mainly includes a metal cover 31 and an inert metal wire 33.

The metal cover 31 has a square tubular shape in this embodiment, but is not limited thereto in actual manufacture.

The inert wire 33 may be made of platinum, rhodium, gold, ruthenium, palladium, iridium, ruthenium, osmium, an alloy of the foregoing metals or stainless steel, and the outer diameter of the inert wire preferably ranges from 100 μm to 150. Mm. In the present embodiment, a platinum wire having an outer diameter of 100 μm was used. Thereby, when the mobile phase liquid of the liquid chromatograph is mixed with the atomizing gas to form aerogel blowing, the degassing gel particles can clean the metal wire, and the inert metal wire can vibrate slightly. The carbon particles are not easily attached, the carbon deposition phenomenon is reduced, and the ion signal is maintained. Thereby, the inert wire 33 can generate a corona phenomenon when a high voltage is applied. Next, the inert wire 33 is fixed to the outer wall surface of the metal cover 31 by welding and is coaxial with the metal cover 31.

Next, referring to the fifth figure, since the conversion assembly 30 is sleeved on the nozzle 11 of the electrospray free device 10, the present invention is shown in the third and fifth figures for the convenience of loading and unloading the conversion assembly 30. The metal cover 31 of the conversion assembly 30 can further include a set of cross reeds 35 disposed on the inner wall surface of the metal cover 31 such that the set of reeds 35 can be interposed between the outer wall of the shower head 11 and The conversion member 30 can be easily and quickly attached to the head 11 by the elasticity of the reed 35 itself between the inner wall faces of the metal cover 31. In actual use, the number of the reeds 35 is not particularly limited as long as the metal cover 31 can be stably placed over the head 11, and for example, a single reed can be used.

In practical applications, as shown in the fifth and sixth figures, the conversion assembly 30 is mounted on the spray head 11 of the electrospray free device 10, and the electrospray free device 10 is mounted on a mass spectrometer. The mass spectrometer includes a mass analyzer 50 having an inlet 53; and the nozzle 11 has an open end 111 for ejecting an atomizing gas 60. The nozzle 11 is internally provided with a metal capillary. 13. The metal capillary 13 has a nozzle end 131 for spraying a sample solution 70 and protruding from the open end 111 of the nozzle. When the conversion assembly 30 is mounted on the shower head 11 of the electrospray free device 10, the distance between the open end 311 of the metal cover 31 and the nozzle end 131 of the metal capillary 13 is preferably in the range of 2 mm to 4 mm. In the present embodiment, it is about 2 mm.

It is worth mentioning that in this embodiment, a Desolvation Gas 62 is also used to assist the evaporation of the solvent in the sample solution 70, but the solvent removal gas 62 can be adjusted according to actual needs.

Next, as shown in the sixth figure, when a high voltage is applied to the head 11, the potential difference between the inner wall surface of the metal cover 31 and the head 11 approaches zero, that is, the inside of the metal cover 31. The electric field is zero, so the free action of the electrospray free device 10 can be destroyed, so that the sample solution 70 does not produce the Taylor cone T as shown in the first figure, in other words, the sample solution 70 is not freed, but from the metal. The nozzle end 131 of the capillary 13 flows out, and is then dispersed by the atomizing gas 60 and the solvent is removed by the solvent removing gas 62, so that the analyte and the solvent in the sample solution 70 are vaporized into gaseous molecules, and then passed through a noble metal to which a high voltage is applied. The tip of the wire 33 is subjected to corona discharge to release the analyte from the gaseous molecules of the solvent, and then reacted via proton transfer or the like to form a charged analyte ion 71', which is equivalent to the free mechanism of the commercial atmospheric pressure chemical free device.

On the other hand, the free device 90 according to another preferred embodiment of the present invention, as shown in the seventh embodiment, mainly includes a nozzle 91, a metal capillary 93 penetrating the nozzle 91, and the metal cover 31. And the inert wire 33, and the metal cover 31 is selectively fixed to the outer wall surface of the shower head 91 through the reed 35, and when the metal cover 31 is fixed to the shower head 91, The distance between the open end 311 of the metal cover 31 and the nozzle end 931 of the metal capillary 93 is preferably in the range of 2 mm to 4 mm. Of course, the free device 90 also has the atomizing gas 60 that can be ejected from the showerhead 91, and the desolvent gas 62 can be optionally used.

The detailed structure, features, and functions of the nozzle 91, the metal capillary 93, the metal cover 31, the inert wire 33, and the reed 35 are the same as those of the shower head 11, the metal capillary 13, and the metal cover 31 in the foregoing embodiments. The inert wire 33 and the reed 35 are the same, and therefore the applicant will not repeat them here.

The present invention will be further clarified by the following experimental examples, which are only to better understand the present invention, and are not intended to limit the scope of the present invention, and those who have ordinary knowledge in the technical field do not violate the inventive spirit of the present invention. Various changes and modifications hereinafter are within the scope of the invention.

In addition, the applicant specifically states here that in the description of the following experimental examples, the electrospray free device is abbreviated as ESI, and the atmospheric pressure chemical free device is abbreviated as APCI. Second, the abscissa of the mass spectrum is the mass-to-charge ratio (m/z), and the ordinate is the relative intensity (%).

<Experimental Example 1>

First, the drug flunitrazepam (commonly known as FM2, taken from Mingsheng Biotechnology Co., Ltd., Mithra Bioindustry Co., Ltd.) having the following structural formula 1 is dissolved in acetonitrile (purity is higher than 95%). , HPLC grade, purchased from JT Baker), formulated into a stock solution at a concentration of 0.14 mg/mL.

When testing, the flunitrazepam stock solution was diluted into 50% (v/v) acetonitrile aqueous solution to a concentration of 1 μg/mL, 5 μg/mL and 10 μg/mL sample solution for ESI and Invention of free devices, and use of APCI.

Thereafter, a three-stage quadrupole mass spectrometer (purchased from Waters, model Quattro Ultima) having a Z-spray atmospheric pressure free (API) interface was used, and the sample solutions were freed and analyzed with ESI, APCI, and the free device of the present invention, each The parameters are set as follows:

Ion source temperature: 80 ° C;

Atomizing gas flow rate: maximum;

Desolvent gas flow rate: 550 L / hr;

Desolvent gas temperature: ESI and the free device positive ion mode of the present invention is 320 ° C, ESI and the free device negative ion mode of the present invention is 400 ° C, and APCI positive and negative ion mode is 550 ° C;

Metal capillary voltage: ESI positive ion mode is 3.0 kV, ESI negative ion mode is 3.2 kV, the free device positive ion mode of the present invention is 2.8 kV, and the free device negative ion mode of the present invention is 3.2 kV;

Corona current: 3.2 μA for APCI positive ion mode and 20 μA for APCI negative ion mode;

The injection cone of the mass analyzer: ESI is 40 V, and the free device of the present invention is 35 V with APCI.

<Experimental Example 2>

The stock solution and the diluted stock solution were prepared in substantially the same manner as in Experimental Example 1 to obtain a sample solution and a test sample solution, except that the drug felodipine (felodipine, which is taken from Mingsheng Biotech Co., Ltd.) Ltd., Mithra Bioindustry Co., Ltd.) is soluble in methanol (HPLC, available from Mallinckrodt Baker, Inc.), formulated into a stock solution at a concentration of 0.5 mg/mL, and utilized 50% ( The v/v) aqueous methanol solution was diluted outside the stock solution. Thereafter, the analysis of the sample solution was carried out by the same apparatus and parameter conditions as in Experimental Example 1.

From the mass spectrum of the eighth panel A to C, it can be found that although the signal of [M] ^{‧ -} can be seen in the negative ion mode detection of ESI, APCI and the free device of the present invention, the signal intensity of the free device of the present invention is 1.65 × 10 ⁹ (Fig. C), similar to the signal strength of APCI 2.27 × 10 ⁹ (Figure B), while the signal intensity of ESI is 9.01 × 10 ⁷ (Figure 8 A), free from APCI and the present invention. The signal strength of the device differs by more than 10 times. Therefore, it can be proved that after the conversion assembly of the present invention is placed on the nozzle of the commercial ESI, the commercial ESI can be successfully converted into a free mechanism of atmospheric pressure chemical release, and the detection result is very similar to the commercial APCI.

Next, please refer to the ninth diagrams A to C. The signal of [M+Na] ⁺ can be seen from the positive ion mode of ESI (the ninth diagram A), but the positive ion mode of the free device and the APCI of the present invention does not appear. Obvious [M+Na] ⁺ signal, in addition, the signal intensity of [MH] ⁺ of the free device of the present invention is 1.59 × 10 ⁸ (Ninth Figure C), and the signal intensity of [MH] ⁺ with APCI is 1.47 × 10 ⁸ (Ninth Figure B) is similar. Furthermore, as shown in the tenth panels A to C, from the ESI negative mode only see [MH] ^- The signal (FIG. A tenth), but in the negative ion mode APCI free device of the present invention, in addition appears [MH In addition to the ^- signal, the [M] ^‧- signal appears, and the signal intensity of [M] ^‧- of the free device of the present invention is 2.96 × 10 ⁸ (the tenth figure C) and the APCI [M] ^{‧ -} signal strength of 1.93 × 10 ⁸ (FIG tenth B) are similar. Therefore, it can be proved that after the conversion assembly of the present invention is placed on the nozzle of the commercial ESI, the commercial ESI can be successfully converted into a free mechanism of atmospheric pressure chemical release, and the detection result is very similar to the commercial APCI.

In summary, since the conversion assembly of the present invention is placed on the nozzle of the commercial electrospray free device, the free mechanism of the electrospray free device can be destroyed, and the inert wire of the present invention is used as a discharge needle for corona discharge. Therefore, it is convenient and quick to convert the electrospray free device into an atmospheric pressure chemical free device, which is convenient to use. In addition, the free device of the present invention can not only achieve a detection result similar to that of the commercial atmospheric pressure chemical free device, but also requires no time-consuming and labor-intensive because the inert metal wire as the discharge needle is less likely to deposit carbon and does not require the use of a heating sleeve. The ion and signal can be maintained by cleaning and polishing. In addition, the present invention facilitates the reduction of the need for commercial atmospheric atmospheric chemical free devices in liquid chromatography mass spectrometry.

10. . . Electrospray free device

11. . . Nozzle

111. . . Open end

13. . . Metal capillary

131. . . Pipe end

20. . . Atmospheric pressure chemical free device

twenty one. . . Metal tube

211. . . Pipe end

twenty three. . . Heating casing

30. . . Conversion component

31. . . Metal cover

311. . . Open end

33. . . Inert metal wire

35. . . Reed

50. . . Quality analyzer

51. . . Injection cone

53. . . Inlet

60. . . Atomizing gas

62. . . Desolvent gas

70. . . Sample solution

71. . . Microdroplet

71’. . . Analyte ion

80. . . Discharge needle

90. . . Free device

91. . . Nozzle

93. . . Metal capillary

931. . . Pipe end

P. . . Power Supplier

T. . . Taylor cone

The first figure is a schematic diagram showing the free mechanism of the commercial electrospray free device;

The second figure is a schematic diagram showing the free mechanism of the commercial atmospheric pressure chemical free device;

The third figure is a perspective view showing a conversion assembly according to a preferred embodiment of the present invention;

The fourth figure is a cross-sectional view of the third figure;

The fifth figure is a schematic view showing the conversion component of the present invention sleeved on the nozzle and the position opposite to the mass analyzer;

Figure 6 is a schematic view showing the possible free mechanism of the conversion assembly of the present invention after being placed on the nozzle;

Figure 7 is a partial cross-sectional view showing the free device according to another preferred embodiment of the present invention;

The eighth graphs A to C are mass spectra showing the detection results of the experimental example 1 of the present invention in the negative ion mode;

The ninth panels A to C are mass spectra showing the detection results of the experimental example 2 of the present invention in the positive ion mode;

Tenth panels A to C are mass spectra showing the results of the detection of the negative ion mode of Experimental Example 2 of the present invention.

30. . . Conversion component

31. . . Metal cover

33. . . Inert metal wire

35. . . Reed

Claims (10)

A conversion assembly for converting an electrospray free device into an atmospheric pressure chemical free device for mounting a sprinkler of an electrospray free device to convert the electrospray free device into an atmospheric pressure chemical free device, wherein the shower head is internally A metal capillary protruding from the open end of the nozzle is disposed, and an atomizing gas is ejected from the open end of the nozzle. The electrospray free device is mounted on a mass spectrometer, and the mass spectrometer includes a mass analysis having an inlet. The conversion assembly includes: a metal cover disposed outside the shower head such that a nozzle end of the metal capillary is located in the metal cover; and an inert metal wire disposed coaxially with the metal cover The metal cover is such that one end of the inert wire can be located on the discharge path of the atomizing gas and is corresponding to the inlet of the mass analyzer. The conversion assembly of claim 1, wherein the metal cover has an open end, and a distance between the open end of the metal cover and the nozzle end of the metal capillary ranges from 2 mm to 4 mm. The conversion assembly of claim 1, wherein the metal cover has a reed disposed between an inner wall surface of the metal cover and an outer wall surface of the shower head for arranging the metal cover Outside the nozzle. The conversion module of claim 1, wherein the inert metal wire is selected from the group consisting of platinum, rhodium, gold, ruthenium, palladium, iridium, osmium, iridium, an alloy of the foregoing metals, and stainless steel. metal. The conversion assembly of claim 1, wherein the inert wire has an outer diameter ranging from 100 μm to 150 μm. A free device installed in a mass spectrometer, the mass spectrometer comprising a mass analyzer having an inlet, the free device comprising: a showerhead having an open end for ejecting an atomizing gas, A metal capillary is disposed inside the nozzle, the metal capillary has a nozzle end for spraying a sample solution and protruding from the open end of the nozzle; a metal cover is sleeved on the outside of the nozzle to make the nozzle of the metal capillary The end is located in the metal cover; and an inert metal wire is disposed coaxially with the metal cover on the metal cover, one end of the inert metal wire is located on the discharge path of the atomizing gas, and is injected into the mass analyzer mouth. The free device of claim 6, wherein the metal cover has an open end, and the distance between the open end of the metal cover and the nozzle end of the metal capillary ranges from 2 mm to 4 mm. The free device of claim 6, wherein the metal cover has a reed disposed between an inner wall surface of the metal cover and an outer wall surface of the shower head for arranging the metal cover Outside the nozzle. The free device according to claim 6, wherein the inert metal wire is selected from the group consisting of platinum, rhodium, gold, ruthenium, palladium, iridium, osmium, iridium, an alloy of the foregoing metals, and stainless steel. metal. The free device of claim 6, wherein the inert wire has an outer diameter ranging from 100 μm to 150 μm.