Detection system for N-bromosuccinimide content in sugammadex sodium

Abstract

The present invention relates to the technical field of detection systems, in particular to a system for detecting the content of N-bromosuccinimide in sodium sugammadex. The system comprises a chromatograph main body for elution and separation and a mass spectrometer main body for detection, wherein a column oven is connected between the chromatograph main body and the mass spectrometer main body, and a chromatographic column for sample elution and separation is assembled in the column oven; a liquid inlet seat and a liquid outlet seat are provided in the column oven, respectively communicating with the chromatograph main body and the mass spectrometer main body, and the chromatographic column is positioned and assembled between the liquid inlet seat and the liquid outlet seat; a telescopic joint structure is provided at the end of the chromatographic column, the chromatographic column is connected to the liquid inlet seat and the liquid outlet seat via the joint structure, and a glass wool column can be positioned and loaded in the joint structure; a combined water bath structure is provided in the column oven based on an inner partition, and the assembled water bath structure can seal the chromatographic column main body structure; the present invention can achieve the purpose of improving the accuracy of content detection.

Description

Technical Field

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

[0002] Sugammadex sodium is an important pharmaceutical excipient widely used in the pharmaceutical, health product, and food industries. Its primary function is to enhance drug bioavailability and help drugs be more efficiently metabolized and eliminated from the body. As the use of sugammadex sodium increases, ensuring its purity and quality becomes increasingly important. During production and quality control, monitoring its impurity content has become a necessary measure to ensure product safety and efficacy. N-bromosuccinimide is a common chemical reagent, commonly used as an oxidant in organic synthesis. However, during the production process of sugammadex sodium, NBS may enter the pharmaceutical preparation and become a potential impurity. Due to the biological activity and reactivity of NBS, its residues may adversely affect the safety and efficacy of drugs. Therefore, accurately detecting and quantifying the content of N-bromosuccinimide in sugammadex sodium is crucial to ensuring product quality.

[0003] Although there are currently a variety of 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, combining the separation power of liquid chromatography with the high sensitivity and selectivity of mass spectrometry. Not only can the molecular weight of a compound be determined, but high-precision quantitative analysis can also 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 instruments, the constant temperature performance of the chromatographic column is poor, which can easily affect the accuracy of the measurement. At the same time, the chromatographic column often experiences sample vaporization and backflow. Currently, glass wool is inserted at both ends of the chromatographic column tube during use. However, the glass wool is difficult to replace when cleaning the chromatographic column tube, which can easily damage 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 background technology.

[0005] To achieve the above-mentioned object, the present invention provides the following technical solution: a detection system for the content of N-bromosuccinimide in sodium sugammadex, comprising a chromatograph body for elution and separation and a mass spectrometer body for detection, a column oven being connected between the chromatograph body and the mass spectrometer body, and a chromatographic column for sample elution and separation being assembled in the column oven; a liquid inlet seat and a liquid outlet seat being respectively connected to the chromatograph body and the mass spectrometer body, and the chromatographic column being positioned and assembled between the liquid inlet seat and the liquid outlet seat; a telescopic The 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 temperature box 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; 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 to 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 the combination of the inner partition, the side panels, the clamping plates and the panels, the main body of the chromatographic column is located in the container, and a water pipe joint is provided 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 engaged 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 engaged 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:

[0009] A casing, which is connected to the threaded joint via an internal thread;

[0010] The 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;

[0011] Side rods are provided on both sides of the telescopic joint, and the side rods are fixedly connected with the inclined plane seats, and the push rods are connected to the inclined plane seats.

[0012] 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 a clip is provided on the upper end plate and the lower end plate, and a socket is provided on the sleeve and the expansion joint, and the clip can be connected to the socket.

[0013] 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 provided 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.

[0014] 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.

[0015] 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.

[0016] 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. The expansion joint and the socket are both provided with a sealing assembly, and the glass wool column is a compressed disposable expansion structure.

[0017] Preferably, the splint is slidably fitted on the inner partition, and a semicircular groove is provided in the middle of the splint, and a sealing gasket is provided in the groove. The two splints can be combined and connected on both sides of the chromatographic column to form an end face.

[0018] Preferably, the detection system performs a process for detecting the content of N-bromosuccinimide, an impurity in sugammadex sodium, 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;

[0019] The chromatographic conditions for detection by the detection system are as follows:

[0020] Chromatographic column: octadecylsilane bonded silica gel is used as filler;

[0021] Mobile phase A: 0.1% formic acid in water;

[0022] Mobile phase B: methanol;

[0023] Flow rate: 1.0 ml / min; injection volume: 50 μl; column temperature: 30°C;

[0024] The mass spectrometry parameters detected by the detection system are as follows:

[0025] Ionization mode: ES1+;

[0026] Single ion detection scan mode, positive ion mode, m / z = 116;

[0027] Drying gas flow: 15L / min;

[0028] Atomizing gas flow rate: 1.5L / min;

[0029] DL tube: 250℃;

[0030] Heating block: 200°C.

[0031] Preferably, the content detection method of the detection system comprises the following steps:

[0032] S1, prepare 0.3% KOH solution, blank solvent, reference solution, and test solution in sequence;

[0033] S2, accurately measure the blank solvent headspace and inject it into the detection system. When the chromatograms of two consecutive injections of blank solution overlap and there are no other abnormal chromatographic peaks, inject the sample for detection;

[0034] S3. Accurately measure 50 μl of the reference solution and the test solution, inject them into the detection system, and record the chromatogram.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1. The detection system of the present invention has high sensitivity and high selectivity, ensuring the accuracy and reliability of the test results. Through the rational design of the column oven, liquid inlet block and liquid outlet block 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, the water bath structure provided in the column oven can ensure effective temperature control of the chromatographic column, maintain the sample separation at the optimal temperature, thereby improving the separation effect and the overall sensitivity of the detection.

[0037] 2. The detection system of the present invention has a modularly designed chromatographic column structure, which can complete the automatic connection process with the combination of the column oven. Both ends of the chromatographic column are provided with 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 a backflow prevention structure can be provided in the joint structure. The backflow prevention component can be deployed along with the telescopic joint, effectively preventing sample backflow, reducing the possibility of sample volatilization and cross contamination, and improving the accuracy and repeatability of the experiment. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1Schematic diagram of the overall structure of the combined instrument of the present invention.

[0039] Figure 2 Schematic diagram of the column oven structure of the present invention.

[0040] Figure 3 Schematic diagram of the column oven of the present invention with the cover opened.

[0041] Figure 4 Schematic diagram of the combined water bath structure of the present invention.

[0042] Figure 5 Schematic diagram of the side plate and chromatographic column structure of the present invention.

[0043] Figure 6 Schematic diagram of the chromatographic column structure of the present invention.

[0044] Figure 7 Schematic diagram of the telescopic joint structure of the present invention.

[0045] Figure 8 Schematic diagram of the panel structure of the present invention.

[0046] Figure 9 Schematic diagram of the panel driving structure of the present invention.

[0047] Figure 10 Schematic diagram of the splint structure of the present invention.

[0048] Figure 11 Schematic diagram of the box cover structure of the present invention.

[0049] Figure 12 The chromatogram is the measurement chromatogram of the blank solution.

[0050] Figure 13 The measured chromatogram is the reference solution.

[0051] Figure 14 This is the first chromatogram of the test solution.

[0052] Figure 15 This is the second chromatogram of the test solution.

[0053] 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. Limiting ring; 12. Threaded joint; 13. Sleeve; 14. Telescopic 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 assembly; 23. Spring slide; 24. Clamp; 25. Shaft seat; 26. Panel; 27. Drive 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

[0054] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments. 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.

[0055] 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 spectrometry instrument, hereinafter referred to as a coupled instrument. The coupled instrument mainly includes two parts: 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.

[0056] like Figure 2 、 Figure 3 As shown, the chromatograph body 1 of the present invention is connected to a column oven 2, a chromatographic column 10 is arranged in the column oven 2 to separate samples, 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, and the liquid inlet seat 6 and the liquid outlet seat 7 are installed through the inner partition 5. The liquid inlet seat 6 is arranged at the top of the inner partition 5, and the liquid outlet seat 7 is arranged at the bottom of the inner partition 5. 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.

[0057] 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 a telescopic joint structure is provided at both ends of the chromatographic column 10. As a component connected to the socket 8, a structure to prevent backflow and backflow can be provided in the joint structure. Threaded joints 12 are provided at both ends of the chromatographic column 10, which can be quickly assembled and disassembled. The sleeve 13 is connected to the threaded joint 12 through an internal thread, and the telescopic joint 14 is slidably installed in the sleeve 13, and an elastic member 15 is connected between the telescopic joint 14 and the inner wall of the sleeve 13. Under the elastic force of the elastic member 15, the telescopic joint 14 can retract in the sleeve 13. After the chromatographic column 10 is fixed in the clamp 9, it can be inserted into the socket 8 by extending the telescopic joint 14. 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, with an upper end plate 17 and a lower end plate 18 at both ends respectively. The upper end plate 17 and the lower end plate 18 are both provided with clips, and the sleeve 13 and the expansion joint 14 are provided with a card seat. The clip can be connected to the card seat 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 play a role in preventing the sample from vaporizing and backflowing. Side rods 19 are provided on both sides of the expansion joint 14. 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, driving the expansion joint 14 to extend.

[0058] like Figure 8 、 Figure 9 As shown, the inner partition 5 of the column oven 2 of the present invention is provided with a combined water bath structure, which is based on the side panels 21 located on both sides of the clamp 9. The side panels 21 are fixed structures, and a resistance wire type heating component 22 is installed thereon, and the upper and lower ends of the side panels 21 are provided with translational clamps 24, and the front part of the side panels 21 is provided with a rotating panel 26. The combination of the inner partition 5, the side panels 21, the clamps 24 and the panel 26 constitutes a closed container. The main part of the chromatographic column 10 is located in the container, and the clamps 24 are provided with a water pipe joint 36, 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 to keep the column oven 2 warm, so that the sample is separated at a suitable temperature.

[0059] like Figure 10As shown, the splint 24 is movably installed by the spring slide 23 installed on the inner partition plate 5. Under normal circumstances, the elastic force of the spring causes the splint 24 to shrink in the direction of the spring slide 23, which will not affect the installation of the chromatographic column 10. A semicircular groove is provided in the middle of the splint 24, in which a sealing gasket is provided. When the splint 24 overcomes the elastic force of the spring and moves, the two splints 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, covering the side plate 21 and the splint 24 to form a closed surface, or rotating to separate and open. The shaft seat 25 is also rotated to install 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 the movable frame 29 is also connected to a rack 30 and a push rod 31. 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, further making the splint 24 move toward the chromatographic column 10 and connect with the chromatographic column 10 to seal 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 seal 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 to the liquid inlet seat 6 and the liquid outlet seat 7.

[0060] like Figure 11 As shown, the extension action of the telescopic joint 14 of the present invention and the assembly action of the sealed container are both carried out as the box cover 4 is merged. A rotating frame 32 is coaxially connected to the driving gear 27, and 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 back 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 provided on the inner seat 34, which is composed of two single magnets respectively installed on both sides of the inner seat 34. The poles of the two single magnets are arranged in opposite directions. When the box cover 4 is closed, the combined magnet 35 simultaneously generates a magnetic force on the single magnetic rod 33. One single magnet generates a repulsive force on the single magnetic rod 33, and the other generates an attractive force on the single magnetic rod 33, thereby causing the driving gear 27 to rotate automatically.

[0061] The process for detecting the content of N-bromosuccinimide, an impurity in sugammadex sodium, using the above detection system is as follows: the potassium hydroxide solution hydrolysis method is used. The main principle is that NBS is heated in a potassium hydroxide aqueous solution to react and produce potassium butyramate. The potassium butyramate is determined by LC-MS to indirectly determine the content of NBS.

[0062] The chromatographic conditions are as follows:

[0063] Chromatographic column 10: Filled with octadecylsilane bonded silica gel (e.g., YMC-Packed AQ-C18 250 x 4.6 mm, 5 μm, or a chromatographic column 10 of equivalent performance);

[0064] Mobile phase A: 0.1% formic acid aqueous solution (1 ml of formic acid is added to 1000 ml of water and shaken well);

[0065] Mobile phase B: methanol;

[0066] Flow rate: 1.0 ml / min; injection volume: 50 μl; column temperature: 30°C;

[0067] The mass spectrometry parameters are as follows:

[0068] Ionization mode: ES1+;

[0069] Single ion detection scan mode (SIM), positive ion mode, m / z = 116;

[0070] Drying gas flow: 15L / min;

[0071] Atomizing gas flow rate: 1.5L / min;

[0072] DL tube: 250℃;

[0073] Heating block: 200°C;

[0074] Perform gradient elution according to the following table:

[0075]

[0076] The preparation methods of each solution are as follows:

[0077] 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.

[0078] Blank solvent: mobile phase A-0.3% KOH solution (4:1).

[0079] Reference solution: Accurately weigh approximately 25 mg of NBS and place in a 50 ml volumetric flask. Dissolve in water and dilute to the mark, then shake well. Accurately measure 1 ml of the above solution and place in a 100 ml volumetric flask. Dilute to the mark with water and shake well. Accurately measure 1 ml of the above solution and place in a 25 ml volumetric flask. Add 5 ml of 0.3% KOH solution and incubate in a 50°C oven for 90 minutes. Remove and cool to room temperature, then dilute to the mark with mobile phase A.

[0080] Test solution: Accurately weigh approximately 500 mg of the product and place in a 25 ml volumetric flask. Dissolve in 5 ml of 0.3% KOH solution. Incubate in a 50°C oven for 90 min. Cool to room temperature and dilute to volume with mobile phase A. Prepare two aliquots.

[0081] When performing the determination, precisely 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.

[0082] Accurately measure 50 μl of each of the reference solution and the test solution, inject them into the detection system, and record the chromatogram. Calculate the N-bromosuccinimide content by peak area using the external standard method, and the concentration should not exceed 9 ppm.

[0083] The measurement chromatogram of the blank solution is as follows Figure 12 As shown, the measured chromatogram of the reference solution is as follows Figure 13 The chromatograms of the two test solutions are shown as follows: Figure 14 、 Figure 15 The sensitivity and recovery of the above measurement process both meet the determination requirements.

[0084] While 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 these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A system for detecting the content of N-bromosuccinimide in sugammadex sodium, 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 to 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 provide a water bath environment for the chromatographic column; The column oven is hinged with a box cover, and the water bath structure automatically disassembles as the box cover is opened and automatically reassembles as the box cover is closed; The joint structure can be extended as the water bath structure is automatically assembled; The water bath structure includes side panels symmetrically arranged on both sides of the chromatographic column, the side panels are fixed to the inner partition, and a heating assembly is installed on the side panels; The water bath structure further includes translational clamping plates provided at the upper and lower ends of the side panels, and a rotatable panel provided at the front of the side panels; A closed container is formed by combining 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 provided on the clamping plate; The splint is movably mounted via a spring slide, and a shaft seat is fixedly mounted in the column oven. A panel and a driving gear are mounted on the shaft seat via a rotating shaft, and the panel can be covered on the side plate and the splint to form a closed surface. A steering gear is rotatably mounted on the shaft seat, the steering gear meshes 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 meshes with the steering gear; The two 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 connected to the threaded joint via an internal thread; An 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 provided on both sides of the telescopic joint, and the side rods are fixedly connected with inclined plane seats, and the push rod is connected to the inclined plane seats.

2. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 1, characterized in that: An anti-backflow component is provided in the sleeve and the expansion joint, and the anti-backflow component includes the glass wool column, and an upper end plate and a lower end plate are provided at both ends of the glass wool column, and a clamp is provided on the upper end plate and the lower end plate. A clamp is provided on the sleeve and the expansion joint, and the clamp can be connected to the clamp.

3. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 1, characterized in that: The driving gear is coaxially connected to a rotating frame, and a single magnetic rod is fixedly installed on one side of the rotating frame; An inner seat is fixedly mounted on the inner wall of the box cover, and a combined magnet is provided on the inner seat. The combined magnet is composed of two single magnets respectively mounted 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.

4. 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 at the top of the inner partition, and the liquid outlet seat is arranged at the bottom of the inner partition. The liquid inlet seat and the liquid outlet seat are both provided with sockets, which can be connected to the joint structure of the chromatographic column.

5. The N-bromosuccinimide content detection system in sugammadex sodium according to claim 4, characterized in that: 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.

6. The system for detecting the content of N-bromosuccinimide in sugammadex sodium according to claim 1, characterized in that: The telescopic 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 telescopic joint and the socket are both provided with a sealing assembly, and the glass wool column is a compressed disposable expansion structure.

7. The system for detecting the content of N-bromosuccinimide in sugammadex sodium according to claim 1, characterized in that: The clamping plate is slidably fitted on the inner partition, 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.

8. The system for detecting the content of N-bromosuccinimide in sugammadex sodium according to claim 1, characterized in that: The detection system is used to detect the content of N-bromosuccinimide, an impurity 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.

9. The system for detecting the content of N-bromosuccinimide in sugammadex sodium according to claim 8, 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 chromatograms 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.

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