A method for detecting the content of sodium chloride in levofloxacin sodium chloride injection

Abstract

The application relates to the technical field of detection methods, and discloses a detection method for the content of sodium chloride in levofloxacin sodium chloride injection, wherein a calibration solution is configured to calibrate a sodium ion selective electrode of a sodium ion analyzer; a sodium ion strength regulator and a masking agent are added into the levofloxacin sodium chloride injection, and stirring is performed until the mixture is uniform, so that a to-be-detected solution is configured; the sodium ion selective electrode of the sodium ion analyzer is used to determine the Na + concentration. Polyethylene imine masking agents are added to reduce the generation of charged organic ions of levofloxacin, reduce the total ion strength of the solution, avoid excessive fluctuation of the total ion strength, cause the determination potential to drift, the linear offset of the standard curve to deviate, and result in the problems that the determined Na + concentration is inaccurate and the conversion result of NaCl deviates greatly. Therefore, the concentrations of Na + and NaCl can be determined more accurately.

Description

Technical Field

[0001] This invention relates to the field of detection methods, specifically a method for detecting the sodium chloride content in levofloxacin sodium chloride injection. Background Technology

[0002] Levofloxacin sodium chloride injection is a compound intravenous infusion. Sodium chloride is a legally required key excipient and osmotic pressure regulator. Its content is a mandatory test item in relevant pharmacopoeias and registration standards, and is directly related to medication safety, formulation stability, and compliance of clinical administration. Therefore, the sodium chloride content in the injection needs to be accurately measured.

[0003] Currently, the main methods for detecting sodium chloride concentration include fluorescein adsorption indicator argentometric method, potentiometric titration argentometric method, sodium ion selective electrode potentiometry, and flame atomic absorption spectrophotometry. Among them, the sodium ion selective electrode potentiometry has the advantages of being fast and simple to operate, but it has the disadvantage of large deviation in the measured concentration, and the electrode is easily contaminated by organic samples over long-term measurement, which affects the accuracy of the measurement. Summary of the Invention

[0004] This invention solves the problem of large deviation and inaccuracy in the existing sodium ion selective electrode method for determining the sodium chloride content in levofloxacin sodium chloride injection.

[0005] The technical solution of this invention is: a method for detecting the sodium chloride content in levofloxacin sodium chloride injection:

[0006] (1) Gradient configuration Na + The standard solution is mixed with sodium ion strength regulator and stirred to prepare a calibration solution. This solution is used to calibrate the sodium ion selective electrode of the sodium ion analyzer until the potential reading stabilizes.

[0007] (2) Add sodium ion strength regulator to levofloxacin sodium chloride injection solution, stir, then add masking agent polyethyleneimine, stir well, and prepare the test solution. Use the sodium ion selective electrode of a sodium ion analyzer to determine Na. + concentration.

[0008] Preferably, (1) Na + The concentration of the standard solution is 10-1000 mg / L.

[0009] Preferably, (1) Na + The ratio of standard solution to sodium ion strength regulator is 1L:(15-25)mL.

[0010] Preferably, the ambient temperature during calibration in (1) is 20-30℃.

[0011] Preferably, the mixing time in (2) is 30-60 min.

[0012] Preferably, in (2), the ratio of levofloxacin sodium chloride injection, sodium ion strength regulator, and masking agent is 1L:(15-25)mL:(0.8-2)g.

[0013] Preferably, the molecular weight of polyethyleneimine in (2) is 600-10000.

[0014] Preferably, the concentration of levofloxacin in levofloxacin sodium chloride injection is 4.95-5.05 g / L.

[0015] Preferably, the sodium chloride concentration in levofloxacin sodium chloride injection is 8.05-9.05 g / L.

[0016] Preferably, the ambient temperature during the measurement in (2) is 20-30℃.

[0017] The beneficial technical effects of this invention are as follows: The sodium ion-selective electrode is used to determine the NaCl concentration of levofloxacin sodium chloride injection solution. Polyethyleneimine is added as a masking agent, which contains multiple amino groups that can form electrostatic interactions with the carboxyl groups of levofloxacin, reducing the generation of charged organic ions from levofloxacin, lowering the total ionic strength of the solution, and avoiding excessive fluctuations in total ionic strength that could cause drift in the measurement potential and linear shift in the standard curve, thus affecting the measured NaCl concentration. + The problem of inaccurate concentration leading to significant deviations in NaCl conversion results can be addressed. Furthermore, levofloxacin, as an amphiphilic organic molecule, binds to polyethyleneimine, reducing its adsorption and deposition on the sodium electrode's sensitive membrane surface. This avoids issues such as decreased electrode response slope and reduced repeatability, thus enabling more accurate determination of NaCl. + And the concentration of NaCl. Detailed Implementation

[0018] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments. The content mentioned in the embodiments is not intended to limit the present invention.

[0019] The sodium ion strength modifier is Orion ISE ion strength modifier 841111, manufactured by Guangzhou Bolate Technology. The average molecular weights of polyethyleneimine are 600, 1200, 1800, and 10000, all sourced from Anaiji Chemical. Polyacrylamide, CAS number 9003-05-8, is from Shenzhen Stole Environmental Protection Technology. The sodium ion analyzer is model TP330, manufactured by Qingdao Lubo Jianye Environmental Protection Technology.

[0020] The concentration of levofloxacin in levofloxacin sodium chloride injection is 5.017 g / L, and the concentration of sodium chloride is 8.993 g / L.

[0021] Example 1:

[0022] (1) Prepare 100 mL of Na solutions with concentrations of 10 mg / L, 100 mg / L, and 1000 mg / L respectively. + Add 2 mL of sodium ion strength regulator to each standard solution (sodium chloride aqueous solution), stir and mix to prepare calibration solutions. At 25℃, use the calibration solutions of different concentrations to calibrate the sodium ion selective electrode of the sodium ion analyzer in sequence until the potential reading is stable.

[0023] (2) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection solution, stir, then add 0.08 g of masking agent polyethyleneimine (average molecular weight 1200), stir and mix for 30 min to prepare the test solution (the actual NaCl concentration in the test solution is 8.8167 g / L). At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the NaCl concentration. + The concentration was calculated and converted to NaCl concentration. The measurement was performed 10 times, and the average value was taken.

[0024] Example 2:

[0025] (1) Prepare 100 mL of Na solutions with concentrations of 10 mg / L, 100 mg / L, and 1000 mg / L respectively. + Add 1.5 mL of sodium ion strength regulator to each standard solution (sodium chloride aqueous solution), stir and mix to prepare calibration solutions. At 25 °C, use the calibration solutions of each concentration to calibrate the sodium ion selective electrode of the sodium ion analyzer in sequence until the potential reading is stable.

[0026] (2) Add 1.5 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection solution, stir, add 0.12 g of masking agent polyethyleneimine (average molecular weight 1800), stir and mix for 40 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0027] Example 3:

[0028] (1) Prepare 100 mL of Na solutions with concentrations of 10 mg / L, 100 mg / L, and 1000 mg / L respectively. + Add 2 mL of sodium ion strength regulator to each standard solution (sodium chloride aqueous solution), stir and mix to prepare calibration solutions. At 25℃, use the calibration solutions of different concentrations to calibrate the sodium ion selective electrode of the sodium ion analyzer in sequence until the potential reading is stable.

[0029] (2) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection solution, stir, add 0.16 g of masking agent polyethyleneimine (average molecular weight 1200), stir and mix for 60 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0030] Example 4:

[0031] (1) Prepare 100 mL of Na solutions with concentrations of 10 mg / L, 100 mg / L, and 1000 mg / L respectively. + Add 2.5 mL of sodium ion strength regulator to each standard solution (sodium chloride aqueous solution), stir and mix to prepare calibration solutions. At 25 °C, use the calibration solutions of each concentration to calibrate the sodium ion selective electrode of the sodium ion analyzer in sequence until the potential reading is stable.

[0032] (2) Add 2.5 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection solution, stir, add 0.2 g of masking agent polyethyleneimine (average molecular weight 1200), stir and mix for 60 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0033] Comparative Example 1 differs from Example 1 in that it does not contain polyethyleneimine.

[0034] (1) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection, stir and mix for 30 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0035] Comparative Example 2 differs from Example 1 in that triethylenetetramine is used instead of polyethyleneimine.

[0036] (1) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection, stir, add 0.08 g of triethylenetetramine, stir and mix for 30 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0037] Comparative Example 3 differs from Example 1 in that polyacrylamide is used instead of polyethyleneimine.

[0038] (1) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection, stir, add 0.08 g of polyacrylamide, stir and mix for 30 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0039] Comparative Example 4 differs from Example 1 in that it uses polyethyleneimine 600 (average molecular weight 600) instead of polyethyleneimine 1200.

[0040] (1) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection, stir, add 0.08 g of polyethyleneimine 600, stir and mix for 30 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0041] Comparative Example 5 differs from Example 1 in that polyethyleneimine 10000 (average molecular weight 10000) is used instead of polyethyleneimine 1200.

[0042] (1) Add 2 mL of sodium ion strength regulator to 100 mL of levofloxacin sodium chloride injection, stir, add 0.08 g of polyethyleneimine 10000, stir and mix for 30 min to prepare the test solution. At 25 °C, use the sodium ion selective electrode of the sodium ion analyzer to determine the Na+ concentration and convert it to NaCl concentration. Measure 10 times and take the average value.

[0043] The absolute value of the deviation rate is the absolute value of (actual NaCl concentration - measured NaCl concentration) / actual NaCl concentration × 100%.

[0044] Table 1 Deviation Rate Test

[0045] Compared with the comparative examples, the measured NaCl concentration of levofloxacin sodium chloride injection in each embodiment was close to the actual concentration, with a low absolute value of deviation, indicating more accurate measurement. This is mainly because polyethyleneimine (average molecular weight 1200-1800) was added as a masking agent. Polyethyleneimine contains multiple amino groups, which can form electrostatic interactions with the carboxyl groups of levofloxacin, reducing the generation of charged organic ions from levofloxacin, lowering the total ionic strength of the solution, and avoiding excessive fluctuations in total ionic strength that could cause drift in the measurement potential and linear shift in the standard curve, leading to incorrect NaCl measurement. +The problem of inaccurate concentration leading to significant deviations in NaCl conversion results can be addressed. Furthermore, levofloxacin, as an amphiphilic organic molecule, binds to polyethyleneimine, reducing its adsorption and deposition on the sodium electrode's sensitive membrane surface. This avoids issues such as decreased electrode response slope and reduced repeatability, thus enabling more accurate determination of NaCl. + And the concentration of NaCl.

[0046] The above embodiments are preferred implementations of the present invention. In addition, the present invention can be implemented in other ways. Any obvious substitutions without departing from the concept of the present invention are within the protection scope of the present invention.

Claims

1. A method for detecting the sodium chloride content in levofloxacin sodium chloride injection, characterized in that, The detection method is as follows: (1) Prepare different concentrations of Na + A standard solution is prepared by adding sodium ion strength regulator, stirring and mixing to form a calibration solution, which is used to calibrate the sodium ion selective electrode of the sodium ion analyzer. (2) Add sodium ion strength regulator to levofloxacin sodium chloride injection, stir, add masking agent, stir well, and prepare the test solution. Use the sodium ion selective electrode of the sodium ion analyzer to determine Na. + concentration.

2. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 1, characterized in that, Na in (1) + The concentration of the standard solution is 10-1000 mg / L.

3. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 1, characterized in that, Na in (1) + The ratio of standard solution to sodium ion strength regulator is 1L:(15-25)mL.

4. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 1, characterized in that, The ambient temperature during calibration in (1) is 20-30℃.

5. The method for detecting the sodium chloride content in levofloxacin sodium chloride injection according to claim 1, characterized in that, The mixing time in (2) is 30-60 min.

6. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 1, characterized in that, The ratio of levofloxacin sodium chloride injection, sodium ion strength regulator, and masking agent in (2) is 1L:(15-25)mL:(0.8-2)g.

7. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 6, characterized in that, The masking agent is polyethyleneimine with a molecular weight of 1200-1800.

8. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 6, characterized in that, The concentration of levofloxacin in the levofloxacin sodium chloride injection is 4.95-5.05 g / L.

9. The method for detecting sodium chloride content in levofloxacin sodium chloride injection according to claim 6, characterized in that, The sodium chloride concentration is 8.05-9.05 g / L.

10. The method for detecting the sodium chloride content in levofloxacin sodium chloride injection according to claim 1, characterized in that, The ambient temperature during the measurement in (2) is 20-30℃.

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