Levofloxacin sodium chloride injection impurity detection equipment

Abstract

The invention relates to the technical field of drug analysis, in particular to levofloxacin sodium chloride injection impurity detection equipment which comprises a detection table, and a sample treatment box, a sample injector, a chromatographic column, a detector and a data collector are arranged on the detection table; a plurality of measuring flasks are arranged in the sample treatment box, a visual camera for monitoring whether sediments exist in the measuring flasks is arranged in the sample treatment box, a PH meter is arranged in each measuring flask, the measuring flasks are connected with a buffer solution box through a buffer solution pipe, and the buffer solution box adds a buffer solution to the measuring flasks through a pump body and the buffer solution pipe so as to adjust the PH of the solution. The method has the characteristics of controlling and improving the dilution quality of the levofloxacin solution and further improving the detection accuracy and efficiency of the levofloxacin sodium chloride injection, and solves the problems that the dilution quality of the levofloxacin solution is poor and the detection accuracy and efficiency of the levofloxacin sodium chloride injection are low due to the fact that precipitates are easily generated in the diluent of the levofloxacin solution in the prior art. And the impurity detection result is influenced.

Description

Technical Field

[0001] The invention relates to the technical field of drug analysis, and in particular to an impurity detection device for levofloxacin sodium chloride injection. Background Art

[0002] Levofloxacin sodium chloride injection is a commonly used antibiotic preparation used to treat a variety of bacterial infections. To ensure its safety and effectiveness, it must be subject to strict quality control, including impurity testing. Impurities may come from raw materials, by-products in the production process, or degradation products. These impurities may have an adverse effect on the safety and efficacy of the drug, so strict testing and control are required.

[0003] During the impurity detection process, the levofloxacin solution needs to be diluted. During the dilution process of the levofloxacin solution, it is easily affected by various factors, resulting in precipitation in the dilution solution and low dilution quality. The dilution quality of the levofloxacin solution directly affects the results of impurity detection. Therefore, we propose an impurity detection device for levofloxacin sodium chloride injection. Summary of the invention

[0004] Based on the technical problems existing in the background technology, the present invention proposes a levofloxacin sodium chloride injection impurity detection device, which has the characteristics of controlling and improving the dilution quality of the levofloxacin solution, thereby improving the accuracy and efficiency of the levofloxacin sodium chloride injection detection, and solves the problem that precipitation is easily generated in the levofloxacin solution diluent in the prior art, resulting in poor dilution quality of the levofloxacin solution, thereby affecting the impurity detection result.

[0005] The present invention provides the following technical scheme: a levofloxacin sodium chloride injection impurity detection device, comprising a detection platform, wherein the detection platform is provided with a sample processing box, an injector, a chromatographic column, a detector and a data collector; the sample processing box is used to input the processed sample into the chromatographic column through the injector, and to detect the sample entering the chromatographic column through the detector, and the data collector is used to collect and process the sample data;

[0006] The sample processing box is provided with a plurality of volume bottles, the sample processing box is provided with a visual camera for monitoring whether there is precipitation in the volume bottle, the volume bottle is provided with a pH meter, the volume bottle is connected to a buffer box through a buffer tube, and the buffer box adds buffer to the volume bottle through a pump body and a buffer tube to adjust the pH of the solution;

[0007] The volumetric bottle is connected with a liquid inlet pipe, a solvent pipe and a liquid outlet pipe, and the liquid outlet pipe is connected with a sample injector.

[0008] Preferably, the measuring bottle is a sealing mechanism with a lid, and a stirring motor is installed on the top, the output shaft of the stirring motor is connected to the stirring rod inside the measuring bottle, a stirring blade is installed at the bottom of the stirring rod, and the stirring motor is used to drive the stirring blade to rotate and mix the solution in the measuring bottle.

[0009] Preferably, a booster pump is installed on the volumetric bottle, and the booster pump is used to draw the gas in the sample processing box into the volumetric bottle, increase the internal pressure of the volumetric bottle, and discharge the solution from the liquid outlet pipe.

[0010] Preferably, an air filter is provided in the sample processing box, and the air filter is used to filter the air entering the sample processing box.

[0011] Preferably, a thermometer is installed in the volumetric flask, and a temperature control mechanism is connected to the sample processing box, and the temperature control mechanism is used to adjust the temperature of the dilution of the solution in the volumetric flask.

[0012] Preferably, a temperature control box is provided inside the temperature control mechanism, and the temperature control box is connected to the air filter of the sample processing box through an air pipe and an air pump. The temperature control box is used to provide hot air and cold air to the sample processing box, and the air filter is used to filter the gas in the temperature control box.

[0013] Preferably, the temperature control box is divided into a heating chamber and a refrigeration chamber by a semiconductor refrigeration sheet, and the semiconductor refrigeration sheet is used to cool the refrigeration chamber and heat the heating chamber at the same time. The refrigeration chamber and the heating chamber are provided with air intake plates.

[0014] Preferably, the air pump is connected to a three-way valve through an air pipe, and the three-way valve is connected to a heating chamber and a refrigeration chamber of the temperature control box through branch pipes.

[0015] Preferably, the liquid inlet pipe, the solvent pipe and the liquid outlet pipe are all provided with flow valves, and a liquid level meter is provided in the measuring bottle.

[0016] Preferably, it also includes a waste liquid tank, and the waste liquid detected by the detector is input into the waste liquid tank through a pipeline, and the waste liquid tank is installed on the supporting legs of the detection platform.

[0017] The invention provides a levofloxacin sodium chloride injection impurity detection device, which monitors whether precipitation is generated during the dilution process by a visual camera, and detects the solution pH value by a pH meter. The precipitation is affected by the solubility of levofloxacin, and the solubility of levofloxacin is affected by the pH value. By setting a buffer box, the pH meter detects the solution pH value, and it can be ensured that it is within a range suitable for the dissolution of levofloxacin, usually 6.0-8.0. If the pH value is too low or too high, an appropriate amount of buffer can be automatically added through the buffer box to adjust the pH value. The buffer adopts a phosphate buffer solution (PBS) or other buffer systems with good biocompatibility. It is ensured that the pH value of the solvent is suitable for the dissolution of levofloxacin. It is avoided that levofloxacin may form precipitation during the dilution process, affecting the uniformity and stability of the solution. The invention solves the problem that precipitation is easily generated in the levofloxacin solution diluent of the prior art, resulting in poor dilution quality of the levofloxacin solution, thereby affecting the impurity detection result. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a schematic diagram of the structure of the present invention;

[0019] Figure 2 This is a schematic diagram of the structure of the sample processing box of the present invention;

[0020] Figure 3 It is a schematic diagram of the structure of the measuring bottle of the present invention;

[0021] Figure 4 It is a schematic diagram of the structure of the temperature control mechanism of the present invention.

[0022] In the figure: 1. test bench; 2. sample processing box; 3. sample injector; 4. chromatographic column; 5. detector; 6. data collector; 7. volumetric bottle; 8. visual camera; 9. liquid inlet pipe; 10. solvent pipe; 11. liquid outlet pipe; 12. air filter; 13. buffer box; 14. pH meter; 15. thermometer; 16. buffer tube; 17. booster pump; 18. stirring motor; 19. stirring rod; 20. stirring blade; 21. liquid outlet flow valve; 22. liquid inlet flow valve; 23. solvent flow valve; 24. temperature control mechanism; 25. air pump; 26. air pipe; 27. three-way valve; 28. branch pipe; 29. ​​temperature control box; 30. semiconductor refrigeration plate; 31. heating chamber; 32. refrigeration chamber; 33. air inlet plate; 34. waste liquid tank; 35. support leg. DETAILED DESCRIPTION

[0023] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, 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 creative work are within the scope of protection of the present invention.

[0024] like Figure 1-3 As shown, the present invention provides a technical solution: a levofloxacin sodium chloride injection impurity detection device, comprising a detection platform 1, on which a sample processing box 2, an injector 3, a chromatographic column 4, a detector 5 and a data collector 6 are arranged; the sample processing box 2 is used to input the processed sample into the chromatographic column 4 through the injector 3, and the sample entering the chromatographic column 4 is detected through the detector 5, and the data collector 6 is used to collect and process the sample data;

[0025] The sample injector 3 is specifically used to accurately inject the sample to be analyzed into the chromatographic system to reduce human operation errors. The automatic sample injector adopts fixed volume injection or sample dilution injection.

[0026] The chromatographic column 4 is a key component for separating and analyzing sample components. It is filled with a solid or liquid solid phase. The components in the sample are separated due to different interaction strengths with the stationary phase. The chromatographic column 4 is any one of a reverse phase chromatographic column, an ion exchange chromatographic column, and a gel permeation chromatographic column.

[0027] The detector 5 is used to monitor the separated components and convert them into data that can be analyzed. The detector 5 uses any one of an ultraviolet visible light (UV-Vis) detector, a fluorescence detector, and a differential refractive index detector. The UV-Vis detector detects components by measuring the absorbance of the sample in the ultraviolet or visible light range.

[0028] The data collector 6 is responsible for acquiring data from the detector 5 and performing analysis and processing. It can monitor the analysis process in real time and provide functions such as data acquisition, peak identification, volume analysis, data storage and report generation.

[0029] Several volume bottles 7 are arranged in the sample processing box 2. A visual camera 8 is arranged in the sample processing box 2 to monitor whether there is precipitation in the volume bottle 7. A pH meter 14 is arranged in the volume bottle 7. The volume bottle 7 is connected to a buffer box 13 through a buffer tube 16. The buffer box 13 adds buffer to the volume bottle 7 through a pump body and a buffer tube 16 to adjust the pH of the solution.

[0030] The volumetric flask 7 is connected with a liquid inlet pipe 9, a solvent pipe 10 and a liquid outlet pipe 11, and the liquid outlet pipe 11 is connected to the sample injector 3. The liquid inlet pipe 9 is used to input levofloxacin sodium chloride injection, and the solvent is input through the solvent pipe 10 for dilution, and the solvent is water-methanol (70:30).

[0031] By setting the buffer box 13, the pH meter 14 detects the solution pH value, which can ensure that it is in the range suitable for the dissolution of levofloxacin, generally 6.0-8.0. If the pH value is too low or too high, an appropriate amount of buffer can be automatically added to adjust the pH value by the buffer box 13. The buffer adopts phosphate buffered saline (PBS) or other good biocompatible buffer systems. Ensure that the pH value of the solvent is suitable for the dissolution of levofloxacin. Avoid levofloxacin from forming precipitation in the dilution process, affecting the uniformity and stability of the solution.

[0032] In another embodiment, the measuring bottle 7 is a sealing mechanism with a cover, and a stirring motor 18 is installed on the top, the output shaft of the stirring motor 18 is connected to the stirring rod 19 inside the measuring bottle 7, and a stirring blade 20 is installed at the bottom of the stirring rod 19. After the solvent is added, the stirring blade 20 is driven by the stirring motor 18 to rotate and fully stir the solution in the measuring bottle 7. Ensure that levofloxacin is completely dissolved. By adopting mechanical stirring, even a large volume of dilution can ensure that the solution is evenly mixed.

[0033] In another embodiment, a booster pump 17 is installed on the volumetric bottle 7, and the booster pump 17 is used to draw the gas in the sample processing box 2 into the volumetric bottle 7, increase the internal pressure of the volumetric bottle 7, and discharge the solution from the liquid outlet pipe 11. The pressure discharge is not only efficient, but also can control the flow rate and the liquid discharge amount is accurate.

[0034] In another embodiment, an air filter 12 is provided in the sample processing box 2, and the air filter 12 is used to filter the air entering the sample processing box 2. During the dilution process of the levofloxacin solution, some microorganisms may degrade or metabolize levofloxacin, thereby reducing the concentration of its active ingredient and affecting the therapeutic effect. The presence of microorganisms may cause chemical changes in other components in the solution, further affecting the effectiveness and safety of the drug. Therefore, it is necessary to perform air filtration, and the air entering the sample processing box 2 is filtered by the high-efficiency air filter 12 to ensure that the particulate matter and microorganisms in the air are effectively removed.

[0035] like Figure 1 and 3 As shown, in another embodiment, a thermometer 15 is installed in the volumetric flask 7 , and a temperature control mechanism 24 is connected to the sample processing box 2 . The temperature control mechanism 24 is used to adjust the temperature of the solution dilution in the volumetric flask 7 .

[0036] Changes in temperature can affect the volume of the solution, resulting in inaccurate dilution ratios. Too low a temperature may also reduce the solubility of levofloxacin, resulting in precipitation formation. Increasing the temperature of the solution can increase the solubility of levofloxacin. The levofloxacin sodium chloride injection is diluted under warm conditions not exceeding 40° C. by the temperature control mechanism 24. The temperature control device can not only increase the temperature, but also decrease the temperature, and can avoid excessive temperatures caused by mechanical stirring or other factors to prevent drug degradation.

[0037] like Figure 4 As shown, a temperature control box 29 is arranged inside the temperature control mechanism 24, and the temperature control box 29 is connected to the air filter 12 of the sample processing box 2 through the air pipe 26 and the air pump 25. The temperature control box 29 is used to provide hot air and cold air for the sample processing box 2, and the air filter 12 is used to filter the gas in the temperature control box 29.

[0038] The temperature control box 29 is divided into a heating chamber 31 and a refrigeration chamber 32 by a semiconductor refrigeration sheet 30. The semiconductor refrigeration sheet 30 is used to cool the refrigeration chamber 32 and heat the heating chamber 31 at the same time. An air inlet plate 33 is provided on the refrigeration chamber 32 and the heating chamber 31. The semiconductor refrigeration sheet 30, also known as a thermoelectric cooler or a Peltier element, is a device based on the thermoelectric effect and can realize the conversion of electrical energy into temperature difference. The cooling side faces the refrigeration chamber 32, and the heating side faces the heating chamber. By cooling the air passing through the refrigeration chamber 32 and the heating chamber, hot air and cold air are obtained.

[0039] The air pump 25 is connected to the three-way valve 27 through the air pipe 26, and the three-way valve 27 is respectively connected to the heating chamber 31 and the refrigeration chamber 32 of the temperature control box 29 through the branch pipe 28. The three-way valve 27 switches the cold air and the hot air as needed, and the cold air and the hot air are filtered through the air filter 12 to remove the particles and microorganisms therein.

[0040] In another embodiment, the liquid inlet pipe 9 is provided with a liquid inlet flow valve 22 for monitoring and controlling the liquid inlet amount of the levofloxacin solution, the solvent pipe 10 is provided with a solvent flow valve 23 for detecting and controlling the amount of solvent added, the liquid outlet pipe 11 is provided with a liquid outlet flow valve 21 for monitoring and controlling the amount of diluted solution, and the measuring bottle 7 is provided with a liquid level meter to detect the remaining amount of the solution and the dilution volume.

[0041] It also includes a waste liquid tank 34. The waste liquid detected by the detector 5 is input into the waste liquid tank 34 through a pipeline. The waste liquid collects the solution after detection to avoid contamination. The waste liquid tank 34 is installed on the legs 35 of the detection platform 1. The temperature control mechanism 24 and the air pump 25 are also installed on the legs 35 of the detection platform 1, which not only saves space but also facilitates maintenance.

[0042] Detection method: The solvent is water-methanol (70:30).

[0043] For test solution, take an appropriate amount of the product and quantitatively dilute it with solvent to make a solution containing approximately 1 mg of levofloxacin per 1 ml.

[0044] For the control solution, accurately measure an appropriate amount of the test solution and quantitatively dilute it with a solvent to prepare a solution containing approximately 2 μg of levofloxacin per 1 ml.

[0045] For the system suitability solution, take an appropriate amount of levofloxacin diformyl impurity reference substance, dissolve it with solvent and dilute it into a solution containing approximately 0.02 mg of levofloxacin diformyl per 1 ml as the impurity stock solution; take approximately 10 mg of levofloxacin reference substance, accurately weigh it, place it in a 10 ml volumetric flask, add 1 ml of the impurity stock solution, dissolve it with solvent and dilute it into a mixed solution containing approximately 1 mg of levofloxacin and 2 μg of levofloxacin diformyl impurity per 1 ml.

[0046] Sensitivity solution: accurately measure an appropriate amount of the control solution and quantitatively dilute it with a solvent to make a solution containing approximately 0.5 μg of levofloxacin per 1 ml.

[0047] Chromatographic conditions: phenylhexyl bonded silica gel as filler; 0.2% formic acid solution-methanol (95:5) as mobile phase A, methanol-acetonitrile (1:1) as mobile phase B, gradient elution according to the table below; flow rate of 0.9 ml per minute; column temperature of 36°C; detection wavelength of 250 nm; injection volume of 25 μl.

[0048]

[0049] System suitability requirements: In the system suitability solution chromatogram, levofloxacin and levofloxacin diformyl impurity should be eluted in sequence, and the separation degree of levofloxacin diformyl impurity and adjacent peaks should meet the requirements. In the sensitivity solution chromatogram, the signal-to-noise ratio of the main component chromatography peak height should be no less than 10.

[0050] Determination method: accurately measure the test solution and the control solution, inject them into the liquid chromatograph respectively, and record the chromatogram.

[0051] The limit is: if there are impurity peaks in the chromatogram of the test solution, the levofloxacin diformyl peak impurity shall be calculated based on the corrected peak area (multiplied by the correction factor 0.49) and shall not be greater than the main peak area of ​​the control solution (0.2%).

[0052] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A levofloxacin sodium chloride injection impurity detection device, characterized in that: The detection platform (1) comprises a sample processing box (2), a sample injector (3), a chromatographic column (4), a detector (5) and a data collector (6); the sample processing box (2) is used to input the processed sample into the chromatographic column (4) through the sample injector (3), and to detect the sample entering the chromatographic column (4) through the detector (5); and the data collector (6) is used to collect and process the sample data; A plurality of measuring bottles (7) are arranged in the sample processing box (2), a visual camera (8) is arranged in the sample processing box (2) for monitoring whether there is precipitation in the measuring bottle (7), a pH meter (14) is arranged in the measuring bottle (7), the measuring bottle (7) is connected to a buffer box (13) via a buffer tube (16), and the buffer box (13) adds buffer to the measuring bottle (7) via a pump body and a buffer tube (16) to adjust the pH of the solution; The volumetric flask (7) is connected with a liquid inlet pipe (9), a solvent pipe (10) and a liquid outlet pipe (11), and the liquid outlet pipe (11) is connected with a sample injector (3).

2. A levofloxacin sodium chloride injection impurity detection device according to claim 1, characterized in that: The measuring bottle (7) is a sealing mechanism with a lid, and a stirring motor (18) is installed on the top. The output shaft of the stirring motor (18) is connected to a stirring rod (19) inside the measuring bottle (7). A stirring blade (20) is installed at the bottom of the stirring rod (19). The stirring motor (18) is used to drive the stirring blade (20) to rotate and mix the solution in the measuring bottle (7).

3. A levofloxacin sodium chloride injection impurity detection device according to claim 1, characterized in that: The volumetric bottle (7) is provided with a booster pump (17), and the booster pump (17) is used to draw the gas in the sample processing box (2) into the volumetric bottle (7), increase the internal pressure of the volumetric bottle (7), and discharge the solution from the liquid outlet pipe (11).

4. A levofloxacin sodium chloride injection impurity detection device according to claim 3, characterized in that: An air filter (12) is arranged in the sample processing box (2), and the air filter (12) is used to filter the air entering the sample processing box (2).

5. A levofloxacin sodium chloride injection impurity detection device according to claim 4, characterized in that: A thermometer (15) is installed in the measuring bottle (7), and a temperature control mechanism (24) is connected to the sample processing box (2). The temperature control mechanism (24) is used to adjust the dilution temperature of the solution in the measuring bottle (7).

6. A levofloxacin sodium chloride injection impurity detection device according to claim 5, characterized in that: A temperature control box (29) is arranged inside the temperature control mechanism (24). The temperature control box (29) is connected to the air filter (12) of the sample processing box (2) through an air pipe (26) and an air pump (25). The temperature control box (29) is used to provide hot air and cold air to the sample processing box (2), and the air filter (12) is used to filter the gas in the temperature control box (29).

7. A levofloxacin sodium chloride injection impurity detection device according to claim 6, characterized in that: The temperature control box (29) is divided into a heating chamber (31) and a refrigeration chamber (32) by a semiconductor refrigeration plate (30). The semiconductor refrigeration plate (30) is used to cool the refrigeration chamber (32) and heat the heating chamber (31) at the same time. The refrigeration chamber (32) and the heating chamber (31) are provided with air intake plates (33).

8. A levofloxacin sodium chloride injection impurity detection device according to claim 7, characterized in that: The air pump (25) is connected to a three-way valve (27) via an air pipe (26), and the three-way valve (27) is respectively connected to a heating chamber (31) and a refrigeration chamber (32) of a temperature control box (29) via a branch pipe (28).

9. A levofloxacin sodium chloride injection impurity detection device according to claim 1, characterized in that: The liquid inlet pipe (9), the solvent pipe (10) and the liquid outlet pipe (11) are all provided with flow valves, and a liquid level meter is provided in the measuring bottle (7).

10. The impurity detection device for levofloxacin sodium chloride injection according to claim 1, characterized in that: It also includes a waste liquid tank (34), into which waste liquid detected by the detector (5) is input through a pipeline, and the waste liquid tank (34) is installed on the supporting legs (35) of the detection platform (1).

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