System for detecting content of N-bromosuccinimide in sugammadex sodium

Abstract

The invention relates to the technical field of detection systems, in particular to a system for detecting the content of N-bromosuccinimide in sugammadex sodium, which comprises a chromatographic instrument main body for elution separation and a mass spectrometer main body for detection, and a column oven is connected between the chromatographic instrument main body and the mass spectrometer main body. A chromatographic column for eluting and separating a sample is assembled in the column oven; a liquid inlet seat and a liquid outlet seat which are respectively communicated with the chromatographic instrument main body and the mass spectrometer main body are arranged in the column oven; the chromatographic column is positioned and assembled between the liquid inlet seat and the liquid outlet seat; a telescopic joint structure is assembled at the end part of the chromatographic column, the chromatographic column is connected with the liquid inlet seat and the liquid outlet seat through the joint structure, and a glass wool column can be positioned and loaded in the joint structure; a combined water bath box structure is arranged in the column oven by means of the inner partition plate, and the combined water bath box structure can seal the main body structure of the chromatographic column; the purpose of improving the content detection precision can be achieved.

Description

Technical Field

[0001] The invention relates to the technical field of detection systems, and in particular to a detection system for the content of N-bromosuccinimide in sugammadex sodium. Background Art

[0002] Sugammadex sodium is an important pharmaceutical excipient, widely used in the pharmaceutical, health care and food industries. Its main function is to enhance the bioavailability of drugs and help drugs metabolize and excrete more effectively. As the application of sugammadex sodium gradually increases, it becomes particularly important to ensure its purity and quality. During the production and quality control process, monitoring the content of its impurities becomes a necessary measure to ensure the safety and effectiveness of the product. N-bromosuccinimide is a common chemical reagent, usually used as an oxidant in organic synthesis. However, during the production process of sugammadex sodium, NBS may enter the drug preparation and become a potential impurity. Due to the biological activity and reactivity of NBS, its residue may have an adverse effect on the safety and efficacy of the drug. Therefore, accurate detection and quantification of the content of N-bromosuccinimide in sugammadex sodium is crucial to ensure the quality of the product.

[0003] Although there are many methods available for detecting impurities in compounds, such as high performance liquid chromatography and gas chromatography, liquid chromatography-mass spectrometry can be used for more effective detection, which combines the separation ability of liquid chromatography with the high sensitivity and selectivity of mass spectrometry. Not only can the molecular weight of the compound be determined, but also high-precision quantitative analysis can be achieved through internal or external standard methods, making it an ideal choice for simultaneous qualitative and quantitative analysis. However, in current liquid chromatography-mass spectrometry, the constant temperature performance of the chromatographic column is poor, which can easily affect the measurement accuracy. At the same time, the chromatographic column often has the situation of sample vaporization backflow. At present, glass wool is inserted at both ends of the chromatographic column tube during use, but the glass wool is not easy to replace when cleaning the chromatographic column tube, which can easily cause damage to the chromatographic column tube. Summary of the invention

[0004] The object of the present invention is to provide a system for detecting the content of N-bromosuccinimide in sugammadex sodium, so as to improve the accuracy of content detection and solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above-mentioned purpose, the present invention provides the following technical scheme: a detection system for the content of N-bromosuccinimide in sodium gluconate, comprising a chromatograph body for elution and separation and a mass spectrometer body for detection, a column oven is connected between the chromatograph body and the mass spectrometer body, and a chromatographic column for sample elution and separation is installed in the column oven; a liquid inlet seat and a liquid outlet seat are provided in the column oven, which are respectively connected to the chromatograph body and the mass spectrometer body, and the chromatographic column is positioned and installed between the liquid inlet seat and the liquid outlet seat; a telescopic The column is connected with the liquid inlet seat and the liquid outlet seat through the joint structure, and the glass wool column can be positioned and loaded in the joint structure; a combined water bath structure is arranged in the column temperature box based on the inner partition, and the combined water bath structure can seal the main structure of the column, and the water bath structure can provide a water bath environment for the column; a box cover is hinged on the column temperature box, and the water bath structure automatically disintegrates as the box cover is opened and automatically assembles as the box cover is closed; the joint structure can be extended as the water bath structure is automatically assembled.

[0006] Preferably, the water bath structure includes side panels symmetrically arranged on both sides of the chromatographic column, and the side panels are fixed on the inner partition, and a heating assembly is installed on the side panels; the water bath structure also includes translational clamping plates arranged at the upper and lower ends of the side panels, and also includes a rotating panel arranged at the front of the side panels; a closed container is formed by a combination of the inner partition, the side panels, the clamping plates and the panel, the main body of the chromatographic column is located in the container, and a water pipe joint is arranged on the clamping plates.

[0007] Preferably, the splint is movably installed by a spring slide rod, and an axle seat is fixedly installed in the column temperature box, a panel and a driving gear are installed on the axle seat through a rotating shaft, and the panel can cover the side panel and the splint to form a closed surface; a steering gear is also rotatably installed on the axle seat, the steering gear is meshed with the driving gear, and a movable frame is fixedly connected to the splint, a rack and a push rod are connected to the movable frame, and the rack is meshed with the steering gear.

[0008] Preferably, threaded joints are provided at both ends of the chromatographic column, and the joint structure is installed through the threaded joints; the joint structure includes: A casing, which is connected to the threaded joint via an internal thread; An expansion joint is slidably mounted in the casing, and an elastic member is connected between the expansion joint and the inner wall of the casing; Side rods are arranged on both sides of the expansion joint, and the side rods are fixedly connected with inclined plane seats, and the push rods are connected with the inclined plane seats.

[0009] Preferably, an anti-backflow component is provided in the sleeve and the expansion joint, and the anti-backflow component includes a glass wool column, and an upper end plate and a lower end plate are respectively provided at both ends of the glass wool column, and clamps are provided on the upper end plate and the lower end plate, and a clamping seat is provided on the sleeve and the expansion joint, and the clamping member can be connected to the clamping seat.

[0010] Preferably, a rotating frame is coaxially connected to the driving gear, and a single magnetic rod is fixedly installed on one side of the rotating frame; an inner seat is fixedly installed on the inner wall of the box cover, and a combined magnet is arranged on the inner seat, which is composed of two single magnets respectively installed on both sides of the inner seat, and the two single magnets are arranged with opposite magnetic poles. The magnetic force generated by the combined magnet on the single magnetic rod can drive the rotating frame to rotate half a circle.

[0011] Preferably, an inner partition is fixedly installed in the middle of the column temperature box, and the liquid inlet seat and the liquid outlet seat are installed through the inner partition. The liquid inlet seat is arranged at the top of the inner partition, and the liquid outlet seat is arranged at the bottom of the inner partition. Sockets are provided on the liquid inlet seat and the liquid outlet seat, which can be connected to the joint structure of the chromatographic column.

[0012] Preferably, two clamps are provided on the inner partition plate to fix the chromatographic column, and a limiting ring is provided on the chromatographic column for positioning.

[0013] Preferably, the expansion joint can be retracted into the sleeve under the elastic force of the elastic member, and can be inserted into the socket after being extended. Both the expansion joint and the socket are provided with a sealing assembly, and the glass wool column is a compressed disposable expansion structure.

[0014] Preferably, the clamping plate is slidably fitted on the inner partition plate, and a semicircular groove is provided in the middle of the clamping plate, and a sealing gasket is provided in the groove, and the two clamping plates can be combined and connected on both sides of the chromatographic column to form an end face.

[0015] Preferably, the detection system detects the content of impurity N-bromosuccinimide in sodium sugammadex as follows: heating NBS in a potassium hydroxide aqueous solution to react and produce potassium butyramate, and then indirectly determining the content of NBS by measuring potassium butyramate; The chromatographic conditions for detection by the detection system are as follows: Chromatographic column: octadecylsilane bonded silica gel is used as filler; Mobile phase A: 0.1% formic acid in water; Mobile phase B: methanol; Flow rate: 1.0 ml / min; injection volume: 50 μl; column temperature: 30°C; The mass spectrometry parameters detected by the detection system are as follows: Ionization mode: ES1+; Single ion detection scan mode, positive ion mode, m / z = 116; Drying gas flow: 15L / min; Atomizing gas flow rate: 1.5L / min; DL tube: 250℃; Heating block: 200 °C.

[0016] Preferably, the content detection method of the detection system comprises the following steps: S1, prepare 0.3% KOH solution, blank solvent, reference solution, and test solution in sequence; S2, accurately measure the blank solvent headspace and inject it into the detection system. When the spectra of two consecutive injections of blank solution overlap and there are no other abnormal chromatographic peaks, inject the sample for detection; S3. Accurately measure 50 μl of the reference solution and the test solution, inject them into the detection system, and record the chromatogram.

[0017] Compared with the prior art, the present invention has the following beneficial effects: 1. The detection system of the present invention has high sensitivity and high selectivity, ensuring the accuracy and reliability of the detection results. By designing a reasonable column temperature box, a liquid inlet seat and a liquid outlet seat structure, the sample preparation and processing process is simplified, the convenience of operation is improved, and the risk of manual intervention is reduced. In addition, a water bath structure is provided in the column temperature box, which can ensure effective temperature control of the chromatographic column and maintain the sample separation at the optimal temperature, thereby improving the separation effect and the overall sensitivity of the detection.

[0018] 2. The detection system of the present invention has a chromatographic column structure with a modular design, which can complete the automatic connection process with the combination of a column oven. Both ends of the chromatographic column have telescopic joints. The use of the telescopic joints and the design of the sealing system allow for quick and convenient modular connection, making the installation and disassembly of the device more convenient, improving the versatility and adaptability of the equipment, and an anti-backflow structure can be set in the joint structure. The anti-backflow component can be deployed with the telescopic joint to effectively prevent sample backflow, reduce the possibility of sample volatilization and cross contamination, and improve the accuracy and repeatability of the experiment. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a schematic diagram of the overall structure of the combined instrument of the present invention.

[0020] Figure 2 It is a schematic diagram of the column oven structure of the present invention.

[0021] Figure 3 It is a schematic diagram of the column oven of the present invention in the open cover state.

[0022] Figure 4 It is a schematic diagram of the combined water bath structure of the present invention.

[0023] Figure 5 It is a schematic diagram of the side plate and chromatographic column structure of the present invention.

[0024] Figure 6 Schematic diagram of the chromatographic column structure of the present invention.

[0025] Figure 7 It is a schematic diagram of the telescopic joint structure of the present invention.

[0026] Figure 8 Schematic diagram of the panel structure of the present invention.

[0027] Fig. 9 Schematic diagram of the panel driving structure of the present invention.

[0028] Fig.10 Schematic diagram of the splint structure of the present invention.

[0029] Fig.11 It is a schematic diagram of the box cover structure of the present invention.

[0030] Fig.12 is the measured chromatogram of the blank solution.

[0031] Fig.13 The measured chromatogram is the reference solution.

[0032] Fig.14 This is the first chromatogram of the test solution.

[0033] Fig.15 This is the second chromatogram of the test solution.

[0034] In the figure: 1. chromatograph body; 2. column oven; 3. mass spectrometer body; 4. box cover; 5. inner partition; 6. liquid inlet seat; 7. liquid outlet seat; 8. socket; 9. clamp; 10. chromatographic column; 11. limit ring; 12. threaded joint; 13. sleeve; 14. expansion joint; 15. elastic part; 16. glass wool column; 17. upper end plate; 18. lower end plate; 19. side rod; 20. inclined seat; 21. side plate; 22. heating component; 23. spring slide rod; 24. splint; 25. shaft seat; 26. panel; 27. driving gear; 28. steering gear; 29. ​​movable frame; 30. rack; 31. push rod; 32. rotating frame; 33. single magnetic rod; 34. inner seat; 35. combined magnet; 36. water pipe joint. DETAILED DESCRIPTION

[0035] The present invention is further described below in conjunction with the accompanying drawings and specific implementation methods. It should be noted that, under the premise of no conflict, the various embodiments or technical features described below can be arbitrarily combined to form a new embodiment. It should be noted that the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0036] See also Figures 1 to 15 The present invention provides a technical solution: Figure 1 As shown, the N-bromosuccinimide content detection system in sugammadex sodium mainly adopts a liquid chromatography-mass spectrometer, hereinafter referred to as a coupled instrument, which mainly includes a chromatograph body 1 and a mass spectrometer body 3. These two parts are used in combination. The sample is first eluted and separated in the chromatograph body 1, and then enters the mass spectrometer body 3 for ionization and detection.

[0037] like Figure 2 , Figure 3 As shown, a column oven 2 is connected to the chromatograph body 1 of the present invention, a chromatographic column 10 is arranged in the column oven 2 for sample separation, and a box cover 4 is hinged on the column oven 2, an inner partition 5 is fixedly installed in the middle of the column oven 2, a liquid inlet seat 6 and a liquid outlet seat 7 are installed through the inner partition 5, the liquid inlet seat 6 is arranged on the top of the inner partition 5, and the liquid outlet seat 7 is arranged at the bottom of the inner partition 5, and sockets 8 are provided on the liquid inlet seat 6 and the liquid outlet seat 7, which can be connected to the chromatographic column 10, so that the sample enters the chromatographic column 10 from the liquid inlet seat 6 along with the mobile phase, and then enters the mass spectrometer body 3 from the liquid outlet seat 7 after separation.

[0038] like Figure 3-Figure 7As shown, two clamps 9 are provided on the inner partition 5, which can fix the chromatographic column 10. In order to ensure that the chromatographic column 10 can be smoothly connected between the liquid inlet seat 6 and the liquid outlet seat 7, a limit ring 11 is provided on the chromatographic column 10 for positioning, and telescopic joint structures are provided at both ends of the chromatographic column 10. As a component connected to the socket 8, a structure for preventing backflow and backflow can be provided in the joint structure. Threaded joints 12 are provided at both ends of the chromatographic column 10, and the joint structure can be quickly assembled and disassembled. The sleeve 13 is connected to the threaded joint 12 through an internal thread, and the expansion joint 14 is slidably installed in the sleeve 13, and an elastic member 15 is connected between the expansion joint 14 and the inner wall of the sleeve 13. Under the elastic force of the elastic member 15, the expansion joint 14 can retract in the sleeve 13, and after the chromatographic column 10 is fixed in the clamp 9, it can be inserted into the socket 8 by extending the expansion joint 14, and both are provided with corresponding sealing The assembly can prevent the sample from flowing out. The sleeve 13 and the expansion joint 14 can be used to install the anti-backflow assembly. The main body of the anti-backflow assembly is a ductile glass wool column 16, and an upper end plate 17 and a lower end plate 18 are respectively arranged at its two ends. The upper end plate 17 and the lower end plate 18 are both provided with clamps, and the sleeve 13 and the expansion joint 14 are provided with a holder, and the clamp can be connected to the holder to fix the upper end plate 17 and the lower end plate 18. The unused glass wool column 16 is usually a compressed compact structure, which is easier to assemble in the sleeve 13. After the expansion joint 14 is extended and connected to the socket 8, the glass wool column 16 can be unfolded, so that the sample can flow out normally with the mobile phase, and at the same time prevent the sample from gasifying and flowing back. Side rods 19 are arranged on both sides of the expansion joint 14, and the side rods 19 are fixedly connected to the inclined seat 20. When the inclined seat 20 is subjected to lateral pressure, it can move to drive the expansion joint 14 to extend.

[0039] like Figure 8 , Fig. 9 As shown, a combined water bath structure is arranged on the inner partition 5 of the column temperature box 2 of the present invention, which is based on the side plates 21 located on both sides of the clamp 9. The side plates 21 are fixed structures, and a resistance wire type heating component 22 is installed thereon, and a translational clamping plate 24 is arranged at the upper and lower ends of the side plates 21, and a rotating panel 26 is arranged at the front of the side plates 21. Through the combination of the inner partition 5, the side plates 21, the clamping plate 24 and the panel 26, a closed container is formed. The main part of the chromatographic column 10 is located in the container, and a water pipe joint 36 is arranged on the clamping plate 24, which can be used to connect the water inlet pipe and the water outlet pipe. When performing detection, the heating liquid is transported into the container through the water inlet pipe and heated by the heating component 22, so as to keep the column temperature box 2 warm and separate the sample at a suitable temperature.

[0040] like Fig.10As shown, the clamping plate 24 is movably installed by the spring slide bar 23 installed on the inner partition plate 5. Under normal circumstances, the elastic force of the spring causes the clamping plate 24 to shrink in the direction of the spring slide bar 23, which will not affect the installation of the chromatographic column 10. A semicircular groove is provided in the middle of the clamping plate 24, in which a sealing gasket is provided. When the clamping plate 24 overcomes the elastic force of the spring and moves, the two clamping plates 24 can be combined and connected on both sides of the chromatographic column 10 to seal its upper and lower ends. At the same time, the inner partition plate 5 is fixedly installed with a shaft seat 25 on both sides of the chromatographic column 10. A panel 26 and a driving gear 27 are installed on the shaft seat 25 through a rotating shaft. When the driving gear 27 drives the rotating shaft to rotate, the panel 26 can rotate accordingly to cover the side plate 21 and the clamping plate 24 to form a closed surface, or rotate to separate and open. The shaft seat 25 is also rotated to install a panel 26 and a driving gear 27. A steering gear 28 is provided, which meshes with the driving gear 27. At the same time, a movable frame 29 is fixedly connected to the splint 24, and a rack 30 and a push rod 31 are connected to the movable frame 29 at the same time. When the driving gear 27 rotates, it can drive the steering gear 28 to rotate, thereby pushing the rack 30 and the movable frame 29 to move, and further, the splint 24 moves toward the chromatographic column 10 and connects with the chromatographic column 10 to close its two ends. At the same time, the panel 26 rotates to the splint 24 and the side plate 21, and cooperates with the inner partition 5 to close the front and back sides, and finally forms a closed container for water bath insulation of the column oven 2. During the movement of the splint 24, the push rod 31 on the movable frame 29 can also be pushed along the inclined seat 20, so that the telescopic joint 14 extends out and is connected with the liquid inlet seat 6 and the liquid outlet seat 7.

[0041] like Fig.11 As shown, the extension action of the telescopic joint 14 and the combination action of the sealed container of the present invention are both carried out as the box cover 4 is merged. A rotating frame 32 is coaxially connected to the driving gear 27. A single magnetic rod 33 is fixedly installed on one side of the rotating frame 32. When there is no force, the two magnetic poles of the single magnetic rod 33 face the front and rear sides of the column temperature box 2, and an inner seat 34 is fixedly installed on the inner wall of the box cover 4. A combined magnet 35 is arranged on the inner seat 34, which is composed of two single magnets respectively installed on both sides of the inner seat 34. The magnetic poles of the two single magnets are arranged oppositely. When the box cover 4 is closed, the combined magnet 35 simultaneously generates magnetic force on the single magnetic rod 33, one single magnet generates repulsive force on the single magnetic rod 33, and the other generates attractive force on the single magnetic rod 33, thereby causing the driving gear 27 to rotate automatically.

[0042] The process for detecting the content of impurity N-bromosuccinimide in sodium sugammadex using the above detection system is as follows. It adopts potassium hydroxide solution hydrolysis method. The main principle is that NBS is heated in potassium hydroxide aqueous solution to react and produce potassium butyramate. Potassium butyramate is determined by LC-MS method to indirectly determine the content of NBS.

[0043] The chromatographic conditions were as follows: Chromatographic column 10: using octadecylsilane bonded silica gel as filler (such as YMC-Packed AQ-C18 250x4.6mm, 5μm or chromatographic column 10 of equivalent performance); Mobile phase A: 0.1% formic acid aqueous solution (measure 1 ml of formic acid, add it to 1000 ml of water, and shake well); Mobile phase B: methanol; Flow rate: 1.0 ml / min; injection volume: 50 μl; column temperature: 30°C; The mass spectrometry parameters are as follows: Ionization mode: ES1+; Single ion detection scan mode (SIM), positive ion mode, m / z=116; Drying gas flow: 15L / min; Atomizing gas flow rate: 1.5L / min; DL tube: 250℃; Heating block: 200°C; Perform gradient elution according to the following table:

[0044] The preparation methods of each solution are as follows: 0.3% KOH solution: Take 300 mg of potassium hydroxide, place it in a 100 ml volumetric flask, dissolve it in water and dilute it to the scale, and shake well.

[0045] Blank solvent: mobile phase A-0.3% KOH solution (4:1).

[0046] Reference solution: Take about 25 mg of NBS, weigh accurately, place in a 50 ml volumetric flask, dissolve with water and dilute to scale, shake well. Accurately measure 1 ml of the above solution, place in a 100 ml volumetric flask, dilute to scale with water, shake well. Accurately measure 1 ml of the above solution, place in a 25 ml volumetric flask, add 5 ml of 0.3% KOH solution, react in a 50 ° C oven for 90 minutes, take out and cool to room temperature, and dilute to scale with mobile phase A.

[0047] Test solution: Take about 500 mg of the product, weigh accurately, place in a 25 ml volumetric flask, add 5 ml of 0.3% KOH solution to dissolve, react in a 50°C oven for 90 min, take out and cool to room temperature, and dilute to scale with mobile phase A. Prepare two parallel copies.

[0048] When conducting the measurement, accurately measure the blank solvent headspace and inject it into the detection system. If the chromatograms of two consecutive injections of blank solutions overlap and there are no other abnormal chromatographic peaks, the sample can be injected for detection.

[0049] Accurately measure 50 μl of the reference solution and the test solution, inject them into the detection system, and record the chromatogram. According to the external standard method, the peak area is calculated, and the N-bromosuccinimide shall not exceed 9 ppm.

[0050] The measured chromatogram of the blank solution is as follows Fig.12 The measured chromatogram of the reference solution is shown in Fig.13 The chromatograms of the two test solutions are shown in Fig.14 , Fig.15 The sensitivity and recovery rate of the above measurement process meet the measurement requirements.

[0051] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A system for detecting the content of N-bromosuccinimide in sodium sugammadex, comprising a chromatograph body for elution and separation and a mass spectrometer body for detection, characterized in that: A column oven is connected between the chromatograph body and the mass spectrometer body, and a chromatographic column for sample elution and separation is installed in the column oven; The column oven is provided with a liquid inlet seat and a liquid outlet seat which are respectively connected with the chromatograph body and the mass spectrometer body, and the chromatographic column is positioned and assembled between the liquid inlet seat and the liquid outlet seat; The end of the chromatographic column is equipped with a telescopic joint structure, and the chromatographic column is connected to the liquid inlet seat and the liquid outlet seat through the joint structure, and the glass wool column can be positioned and loaded in the joint structure; The column oven is provided with a combined water bath structure based on the inner partition, and the combined water bath structure can seal the main structure of the chromatographic column, and the water bath structure can provide a water bath environment for the chromatographic column; The column oven is hinged with a box cover, and the water bath box structure automatically disassembles as the box cover is opened and automatically assembles as the box cover is closed; The joint structure can be extended along with the automatic assembly of the water bath structure.

2. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 1, characterized in that: The water bath structure comprises side plates symmetrically arranged on both sides of the chromatographic column, the side plates are fixed on the inner partition plate, and a heating assembly is installed on the side plates; The water bath structure also includes translational clamping plates arranged at the upper and lower ends of the side plates, and a rotating panel arranged at the front of the side plates; A closed container is formed by the combination of an inner partition, a side plate, a clamping plate and a panel. The main body of the chromatographic column is located in the container, and a water pipe joint is arranged on the clamping plate.

3. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 2, characterized in that: The clamping plate is movably installed through a spring slide rod, and a shaft seat is fixedly installed in the column temperature box, a panel and a driving gear are installed on the shaft seat through a rotating shaft, and the panel can cover the side plate and the clamping plate to form a closed surface; A steering gear is rotatably mounted on the shaft seat, the steering gear is meshed with the driving gear, and a movable frame is fixedly connected to the clamping plate, a rack and a push rod are connected to the movable frame, and the rack is meshed with the steering gear.

4. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 3, characterized in that: Both ends of the chromatographic column are provided with threaded joints, and the joint structure is installed through the threaded joints; The joint structure comprises: A sleeve, the sleeve being connected to the threaded joint via an internal thread; An expansion joint, wherein the expansion joint is slidably mounted in the sleeve, and an elastic member is connected between the expansion joint and the inner wall of the sleeve; Side rods are arranged on both sides of the telescopic joint, and the side rods are fixedly connected with inclined plane seats, and the push rod is connected with the inclined plane seats.

5. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 4, characterized in that: The sleeve and the expansion joint are provided with an anti-backflow component, which includes the glass wool column, and the upper end plate and the lower end plate are respectively provided at both ends of the glass wool column, and the upper end plate and the lower end plate are both provided with clamps, and the sleeve and the expansion joint are provided with a clamping seat, and the clamping member can be connected to the clamping seat.

6. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 3, characterized in that: A rotating frame is coaxially connected to the driving gear, and a single magnetic rod is fixedly installed on one side of the rotating frame; An inner seat is fixedly installed on the inner wall of the box cover, and a combined magnet is arranged on the inner seat. The combined magnet is composed of two single magnets respectively installed on both sides of the inner seat, and the two single magnets are arranged with opposite magnetic poles. The magnetic force generated by the combined magnet on the single magnetic rod can drive the rotating frame to rotate half a circle.

7. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 1, characterized in that: An inner partition is fixedly installed in the middle of the column temperature box, and the liquid inlet seat and the liquid outlet seat are installed through the inner partition. The liquid inlet seat is arranged on the top of the inner partition, and the liquid outlet seat is arranged on the bottom of the inner partition. Sockets are arranged on the liquid inlet seat and the liquid outlet seat, which can be connected to the joint structure of the chromatographic column.

8. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 7, characterized in that: The inner partition is provided with two clamps for fixing the chromatographic column, and a limiting ring is provided on the chromatographic column for positioning.

9. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 4, characterized in that: The expansion joint can be retracted into the sleeve under the elastic force of the elastic member, and can be inserted into the socket after being extended. The expansion joint and the socket are both provided with sealing components, and the glass wool column is a compressed disposable expansion structure.

10. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 1, characterized in that: The clamping plate is slidably fitted on the inner partition plate, and a semicircular groove is provided in the middle of the clamping plate, and a sealing gasket is provided in the groove. The two clamping plates can be combined and connected on both sides of the chromatographic column to form an end face.

11. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 1, characterized in that: The detection system is used to detect the content of impurity N-bromosuccinimide in sodium sugammadex. The process is as follows: NBS is heated in a potassium hydroxide aqueous solution to react and produce potassium butyramate, and then the content of NBS is indirectly determined by measuring the potassium butyramate; The chromatographic conditions for detection by the detection system are as follows: Chromatographic column: octadecylsilane bonded silica gel is used as filler; Mobile phase A: 0.1% formic acid in water; Mobile phase B: methanol; Flow rate: 1.0 ml / min; injection volume: 50 μl; column temperature: 30°C; The mass spectrometry parameters detected by the detection system are as follows: Ionization mode: ES1+; Single ion detection scan mode, positive ion mode, m / z = 116; Drying gas flow: 15L / min; Atomizing gas flow rate: 1.5L / min; DL tube: 250℃; Heating block: 200 °C.

12. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 11, characterized in that: The content detection method of the detection system comprises the following steps: S1, prepare 0.3% KOH solution, blank solvent, reference solution, and test solution in sequence; S2, accurately measure the blank solvent headspace and inject it into the detection system. When the spectra of two consecutive injections of blank solutions overlap and there are no other abnormal chromatographic peaks, inject the sample for detection; S3, accurately measure 50 μl of the reference solution and the test solution, inject them into the detection system, and record the chromatogram.

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