Liquid chromatography detection method for moxifloxacin degradation impurity J and application of liquid chromatography detection method

Abstract

The invention relates to the technical field of analytical chemistry, and particularly discloses a liquid chromatography detection method for a moxifloxacin degradation impurity J and application of the liquid chromatography detection method. The liquid chromatography detection method for the moxifloxacin degradation impurity J provided by the invention comprises the following steps: preparing a reference substance solution, preparing a test solution, and carrying out liquid chromatography detection, liquid chromatography detection: injecting the reference substance solution and the test solution into a liquid chromatograph, and carrying out separation detection by adopting a mobile phase gradient elution method; a used chromatographic column is a chromatographic column with phenyl bonded silica gel as a filler; the mobile phase A is a buffer solution containing sodium octanesulfonate, diethylamine and tetrabutylammonium hydrogen sulfate, and the mobile phase B is methanol. The liquid chromatography detection method provided by the invention can be used for rapidly and accurately detecting the cifloxacin degradation impurity J in the moxifloxacin hydrochloride sodium chloride injection, the detection accuracy is good, the sensitivity is high, the reliability is good, and the quality control of the moxifloxacin hydrochloride sodium chloride injection can be realized.

Description

Technical Field

[0001] The present application relates to the technical field of analytical chemistry, and in particular to a liquid chromatography detection method for moxifloxacin degradation impurity J and its application. Background Art

[0002] As an efficient separation and analysis technology, liquid chromatography plays an important role in drug component detection. For drug quality control, accurate determination of trace impurities in drugs and their metabolites is crucial, which is not only related to the effectiveness and safety evaluation of drugs, but also directly determines the competitiveness and technical level of pharmaceutical companies. In order to ensure the consistency and reliability of drug quality, researchers are constantly exploring more accurate and effective detection methods.

[0003] Existing liquid chromatography detection methods usually involve the selection of multiple detection conditions, such as using different types of chromatographic columns and optimizing the composition of the mobile phase to achieve effective separation of the target compound and its impurities. Common practical operations include but are not limited to selecting a C18 reverse phase column, adjusting the pH value, changing the proportion of organic solvents, etc., in order to better meet the separation requirements of specific drug components. In addition, the separation efficiency can be further improved by fine-tuning factors such as temperature and flow rate.

[0004] However, in actual operation, it is found that for the detection of certain specific compounds such as moxifloxacin and its degradation products, it is often difficult to achieve the ideal separation effect under the above-mentioned general detection conditions, especially the insufficient sensitivity for the detection of low-concentration impurities, which cannot effectively meet the requirements of modern drug quality control. Summary of the invention

[0005] In order to improve the accuracy and sensitivity of detecting the content of moxifloxacin degradation impurity J, the present application provides a liquid chromatography detection method for moxifloxacin degradation impurity J and application thereof.

[0006] In the first aspect, the present application provides a liquid chromatography detection method for moxifloxacin degradation impurity J, which adopts the following technical solution: A liquid chromatography detection method for moxifloxacin degradation impurity J, comprising the following steps: preparing a reference solution, preparing a test solution, and performing liquid chromatography detection; Liquid chromatography detection: The reference solution and the test solution are injected into the liquid chromatograph, and the mobile phase gradient elution method is used for separation and detection; the chromatographic column used is a chromatographic column filled with phenyl bonded silica gel; The mobile phase gradient elution process is as follows: at 0-10 min, mobile phase A is 100% and mobile phase B is 0%; at 10-35 min, mobile phase A is linearly reduced to 72% and mobile phase B is linearly increased to 28%; at 35-40 min, mobile phase A is 72% and mobile phase B is 28%; at 40-45 min, mobile phase A is linearly increased to 100% and mobile phase B is linearly reduced to 0%; at 45-50 min, mobile phase A is 100% and mobile phase B is 0%; mobile phase A and mobile phase B are both measured in volume percentages; The mobile phase A is a buffer solution containing sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate, and the mobile phase B is methanol.

[0007] The present application develops a liquid chromatography detection method for moxifloxacin degradation impurity J by adjusting the type and ratio of the mobile phase and designing the mobile phase gradient elution conditions. The detection method can quickly and accurately detect the moxifloxacin degradation impurity J in moxifloxacin hydrochloride sodium chloride injection, and the detection accuracy is good, the sensitivity is high, and the reliability is good. The above detection method is used in the production of moxifloxacin hydrochloride sodium chloride injection, which can effectively control the quality of moxifloxacin hydrochloride sodium chloride injection. Specifically, the present application uses a buffer solution of sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate as the mobile phase A, which can make each substance in the moxifloxacin hydrochloride sodium chloride injection fully eluted in turn, and the separation between the peaks in the obtained chromatographic peaks is good, the peak shape is symmetrical, and the detection result of moxifloxacin degradation impurity J is highly accurate.

[0008] Optionally, in the mobile phase A, the concentration of sodium octane sulfonate is 0.2-0.4 g / L, the concentration of diethylamine is 0.4-0.6 g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4-0.6 g / L.

[0009] In the present application, the concentrations of sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate in mobile phase A will affect the separation effect of moxifloxacin degradation impurity J in the chromatogram and its peak shape symmetry, thereby affecting the accuracy and repeatability of the test results. Through experimental exploration, the present application found that by further controlling the concentrations of sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate in mobile phase A within the above range, the peak shape of the target peak in the obtained chromatogram is good in symmetry, without tailing, and difficult baseline separation, and the detection results of the content of moxifloxacin degradation impurity J in the test solution are more stable and repeatable, and the RSD of the content detection results can be as low as 3.00% or less.

[0010] Optionally, the preparation method of the mobile phase A is: dissolving sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate in a phosphate buffer to prepare the mobile phase A; in the phosphate buffer, the concentration of disodium hydrogen phosphate is 30 g / L, the concentration of phosphoric acid is 25 g / L, and the pH value of the phosphate buffer is adjusted to 5.6 by triethylamine. Optionally, in the liquid chromatography detection, the flow rate of the mobile phase is 1.2-1.4 mL / min.

[0011] Optionally, in the liquid chromatography detection, the column temperature is 35-45°C.

[0012] Optionally, in the liquid chromatography detection, the detection wavelength is 293 nm.

[0013] Optionally, in the liquid chromatography detection, the chromatographic column is Kromasil 100-5-phenyl, 250mm×4.6mm, 5μm.

[0014] Optionally, the detection limit of the moxifloxacin degradation impurity J is 0.003 μg / mL, and the quantification limit is 0.01 μg / mL.

[0015] In a second aspect, the liquid chromatography detection method for moxifloxacin degradation impurity J provided in the present application is used in the detection of moxifloxacin degradation impurity J in moxifloxacin hydrochloride and sodium chloride injection.

[0016] In summary, this application has the following beneficial effects: 1. The present application provides a liquid chromatography detection method for moxifloxacin degradation impurity J, which uses a chromatographic column filled with phenyl bonded silica gel, and adopts a specific mobile phase and gradient elution program, so that the content of moxifloxacin degradation impurity J in moxifloxacin hydrochloride sodium chloride injection can be quickly and accurately detected, and the detection has good accuracy, high sensitivity and good reliability, and can achieve the quality control value of moxifloxacin hydrochloride sodium chloride injection.

[0017] 2. The detection method provided in this application detects the content of moxifloxacin degradation impurity J in moxifloxacin hydrochloride and sodium chloride injection. The detection limit of moxifloxacin degradation impurity J is 0.003 μg / mL, and the quantification limit is 0.01 μg / mL.

[0018] 3. The present application further controls the content of each component in mobile phase A within the following range: the concentration of sodium octane sulfonate is 0.2-0.4 g / L, the concentration of diethylamine is 0.4-0.6 g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4-0.6 g / L. The obtained detection method has better stability and repeatability, and the RSD value of the detection result can be reduced to below 3.00%. DETAILED DESCRIPTION

[0019] The present application provides a liquid chromatography detection method for moxifloxacin degradation impurity J, comprising the following steps: (1) Preparation of reference substance solution: 2 mg of precise moxifloxacin degradation impurity J reference substance was placed in a 25 ml volumetric flask, dissolved in methanol and diluted to scale, shaken well to obtain reference substance stock solution; 1 mL of precise reference substance stock solution was placed in a 10 ml volumetric flask, diluted to scale with diluent, shaken well to obtain reference substance solution; The preparation method of the diluent is as follows: dissolving anhydrous sodium sulfite in tetrabutylammonium hydrogen sulfate buffer to obtain a diluent with an anhydrous sodium sulfite concentration of 20 mg / L; The preparation method of the tetrabutylammonium hydrogen sulfate buffer is as follows: 0.5 g of tetrabutylammonium hydrogen sulfate, 1.0 g of potassium dihydrogen phosphate and 2 mL of phosphoric acid are added into water to dissolve, and water is added to make the volume to 1000 mL to prepare the tetrabutylammonium hydrogen sulfate buffer.

[0020] (2) Preparation of test solution: Take 5 mL of moxifloxacin hydrochloride and sodium chloride injection, accurately weigh it, place it in a 10 mL volumetric flask, dilute it to the mark with diluent, shake well, and obtain the test solution.

[0021] (3) Liquid chromatography detection: 30 μL of the reference solution and the test solution were respectively taken and injected into the liquid chromatograph. The content of the moxifloxacin degradation impurity J was calculated based on the peak areas of the standard solution and the test solution. The liquid chromatography detection conditions were as follows: a Kromasil 100-5-phenyl column with a specification of 250 mm × 4.6 mm, 5 μm, a mobile phase flow rate of 1.2-1.4 mL / min, an injection volume of 20-30 μL, a column temperature of 35-45°C, and a detection wavelength of 293 nm.

[0022] The mobile phase gradient elution program is: at 0-10min, mobile phase A is 100%, and mobile phase B is 0%; at 10-35min, mobile phase A linearly decreases to 72%, and mobile phase B linearly increases to 28%; at 35-40min, mobile phase A is 72%, and mobile phase B is 28%; at 40-45min, mobile phase A linearly increases to 100%, and mobile phase B linearly decreases to 0%; at 45-50min, mobile phase A is 100%, and mobile phase B is 0%; mobile phase A and mobile phase B are both measured in volume percentage; the mobile phase A is a buffer solution containing sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate, and the mobile phase B is methanol. Further, in the mobile phase A, the concentration of sodium octane sulfonate is 0.2-0.4g / L, the concentration of diethylamine is 0.4-0.6g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4-0.6g / L.

[0023] In this application, the batch number of moxifloxacin hydrochloride sodium chloride injection is 2001131, the specification is 250mL, containing 0.4g of moxifloxacin and 2.0g of sodium chloride; the reference substance of cifloxacin degradation impurity J is 1-cyclopropyl-8-methoxy-6-fluoro-1,4-dihydro-7-[(4aS, 7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxoquinoline, CAS No. 1322062-57-6; the CAS No. of sodium octane sulfonate is 207596-29-0, and the CAS No. of tetrabutylammonium hydrogen sulfate is 250-27-8. The raw materials, reagents, solvents, etc. used in this application can all be obtained commercially.

[0024] The present application is further described in detail below in conjunction with embodiments and performance testing experiments.

[0025] Example 1 Embodiment 1 provides a liquid chromatography detection method for moxifloxacin degradation impurity J, comprising the following steps: (1) Preparation of reference substance solution: 2 mg of precise moxifloxacin degradation impurity J reference substance was placed in a 25 ml volumetric flask, dissolved in methanol and diluted to scale, shaken well to obtain reference substance stock solution; 1 mL of precise reference substance stock solution was placed in a 10 ml volumetric flask, diluted to scale with diluent, shaken well to obtain reference substance solution; The preparation method of the diluent is as follows: dissolving anhydrous sodium sulfite in tetrabutylammonium hydrogen sulfate buffer to obtain a diluent with an anhydrous sodium sulfite concentration of 20 mg / L; The preparation method of the tetrabutylammonium hydrogen sulfate buffer is as follows: 0.5 g of tetrabutylammonium hydrogen sulfate, 1.0 g of potassium dihydrogen phosphate and 2 mL of phosphoric acid are added into water to dissolve, and water is added to make the volume to 1000 mL to prepare the tetrabutylammonium hydrogen sulfate buffer.

[0026] (2) Preparation of test solution: Take 5 mL of moxifloxacin hydrochloride and sodium chloride injection, accurately weigh it, place it in a 10 mL volumetric flask, dilute it to the mark with diluent, shake well, and obtain the test solution.

[0027] (3) Liquid chromatography detection: 30 μL of the reference solution and the test solution were respectively taken and injected into the liquid chromatograph. The content of the moxifloxacin degradation impurity J was calculated based on the peak areas of the standard solution and the test solution. The liquid chromatography detection conditions were as follows: a Kromasil 100-5-phenyl column with a specification of 250 mm × 4.6 mm, 5 μm, a mobile phase flow rate of 1.2 mL / min, an injection volume of 25 μL, a column temperature of 40°C, and a detection wavelength of 293 nm.

[0028] The mobile phase gradient elution program was as follows: 0-10 min, mobile phase A was 100%, mobile phase B was 0%; 10-35 min, mobile phase A was linearly reduced to 72%, mobile phase B was linearly increased to 28%; 35-40 min, mobile phase A was 72%, mobile phase B was 28%; 40-45 min, mobile phase A was linearly increased to 100%, mobile phase B was linearly reduced to 0%; 45-50 min, mobile phase A was 100%, mobile phase B was 0%; mobile phase A and mobile phase B were linearly increased to 100%, mobile phase B was linearly decreased to 0%; Phase B is measured in volume percentage; in Example 1, the preparation method of mobile phase A is: sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate are dissolved in phosphate buffer, so that the concentration of sodium octane sulfonate is 0.3g / L, the concentration of diethylamine is 0.4g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4g / L, and mobile phase A is obtained; in the phosphate buffer, the concentration of disodium hydrogen phosphate is 30g / L, the concentration of phosphoric acid is 25g / L, and the pH value of the phosphate buffer is adjusted to 5.6 by triethylamine. Mobile phase B is methanol.

[0029] 1. Repeatability Six test sample solutions (1-6) were prepared in parallel, and the reference sample solution and the test sample solution were injected into a liquid chromatograph. The test was performed according to the method provided in Example 1, and the chromatogram was recorded. The results are shown in Table 1 below.

[0030] Table 1 Repeatability test results According to the test results in Table 1, 6 groups of test solutions were tested in parallel using the test method provided in Example 1 of the present application, and the average value of the test results was 0.0140%, and the RSD value of the test results was 2.31. Therefore, it is shown that the liquid chromatography detection method for moxifloxacin degradation impurity J provided in the present application can be used to determine the content of moxifloxacin degradation impurity J in moxifloxacin hydrochloride sodium chloride injection, and the detection repeatability is good.

[0031] (II) Instrument precision The reference solution was accurately measured and injected into a liquid chromatograph, and the sample was injected six times continuously according to the chromatographic conditions of step (3) in Example 1, and the chromatogram was recorded. The test results are shown in Table 2 below.

[0032] Table 2 Precision test results Injection times Retention time (min) Peak area 1 24.217 206543 2 24.194 205687 3 24.176 205950 4 24.167 204566 5 24.161 205123 6 24.088 204638 RSD(%) 0.18 0.38 From the test results in Table 2, it can be seen that the reference solution was injected 6 times continuously, the RSD value of the retention time was 0.18% (≤2.0%), and the RSD value of the peak area was 0.38% (≤2.0%). Therefore, it is shown that the instrument precision of the liquid chromatography detection method for moxifloxacin degradation impurity J provided in this application is good.

[0033] (III) Limit of quantitation, detection limit and repeatability of limit of quantitation (1) Limit of quantification and limit of detection: A reference solution with a concentration of 0.008 mg / mL was prepared according to the method in Example 1, and then the reference solution was diluted step by step according to the peak height signal-to-noise ratio of the reference solution. When the peak height signal-to-noise ratio S / N ≥ 10:1, this concentration was used as the limit of quantification; when the peak height signal-to-noise ratio S / N ≥ 3:1, this concentration was used as the limit of detection. The results are shown in Table 3 below. (2) Repeatability of limit of quantitation: Six solutions of limit of quantitation (1-6) were prepared in parallel and tested under the liquid chromatography conditions of Example 1, and the RSD values ​​of the peak areas were calculated. The results are shown in Table 4 below.

[0034] Table 3 Test results of quantitation limit and detection limit Table 4 Test results of repeatability of quantitation limit name Peak area Quantitative limit solution-1 1990 Quantitative limit solution-2 1998 Quantitative limit solution-3 2071 Quantitative limit solution-4 2151 Quantitative limit solution-5 2150 Quantitative limit solution-6 2038 RSD(%) 3.46 It can be seen from the test results in Table 3 and Table 4 that the detection method provided in the present application has high sensitivity and good repeatability, and the detection limit of moxifloxacin degradation impurity J can be as low as 0.003 ng / mL, and the quantitative limit can be as low as 0.01 ng / mL.

[0035] Example 2-11 Examples 2-11 respectively provide a liquid chromatography detection method for a degradation impurity J of moxifloxacin.

[0036] The difference between the above embodiment and embodiment 1 is that the concentration of each substance in mobile phase A is specifically shown in Table 5 below.

[0037] Table 5 Concentration of each substance in mobile phase A in the detection method provided in Examples 2-11 Comparative Example 1 Comparative Example 1 provides a liquid chromatography detection method for moxifloxacin degradation impurity J.

[0038] The difference between the comparative example and Example 1 is that the mobile phase A is a buffer solution containing diethylamine and tetrabutylammonium hydrogen sulfate; wherein the concentration of diethylamine is 0.4 g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4 g / L.

[0039] Comparative Example 2 Comparative Example 2 provides a liquid chromatography detection method for moxifloxacin degradation impurity J.

[0040] The difference between the comparative example and Example 1 is that the mobile phase A is a buffer solution containing sodium octane sulfonate and tetrabutylammonium hydrogen sulfate; wherein the concentration of sodium octane sulfonate is 0.2 g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4 g / L.

[0041] Comparative Example 3 Comparative Example 3 provides a liquid chromatography detection method for moxifloxacin degradation impurity J.

[0042] The difference between the comparative example and Example 1 is that: isocratic elution of the mobile phase is adopted in the liquid chromatography detection process; the ratio of the mobile phase is: 0.5 g / L tetrabutylammonium hydrogen sulfate aqueous solution: methanol = 72:28.

[0043] Comparative Example 4 Comparative Example 4 provides a liquid chromatography detection method for moxifloxacin degradation impurity J.

[0044] The difference between the comparative example and Example 1 is: the mobile phase gradient elution process.

[0045] The mobile phase gradient elution process of Comparative Example 4 is as follows: at 0-60min, mobile phase A is 100%, and mobile phase B is 0%; at 60-85min, mobile phase A is linearly reduced to 0%, and mobile phase B is linearly increased to 100%; at 85-95min, mobile phase A is 0%, and mobile phase B is 0%; at 95-95.01min, mobile phase A is increased to 100%, and mobile phase B is reduced to 0%; at 95.01-120min, mobile phase A is 100%, and mobile phase B is 100%; mobile phase A and mobile phase B are both measured in volume percentage; Among them, mobile phase A is phosphate buffer, methanol and acetonitrile in a volume ratio of 75:12:13, and mobile phase B is phosphate buffer, methanol and acetonitrile in a volume ratio of 40:27:33; in the phosphate buffer, the concentration of disodium hydrogen phosphate is 30 g / L, the concentration of phosphoric acid is 25 g / L, and the pH value of the phosphate buffer is adjusted to 5.6 by triethylamine.

[0046] Test results A reference solution and a test solution were prepared separately (6 portions were prepared in parallel), and then the reference solution and the test solution were injected into a liquid chromatograph, and the detection was performed according to the methods provided in Examples 1-11 and Comparative Examples 1-4, respectively. The content of moxifloxacin degradation impurity J in the test solution was obtained according to the chromatogram, and the average value and RSD value of the detection results obtained by each method were taken. The results are shown in Table 6 below.

[0047] Table 6 Test results obtained by the methods provided in Examples 1-11 and Comparative Examples 1-4 According to the test results in Table 6, the content of moxifloxacin degradation impurity J in the test solution obtained by the method provided in Examples 1-11 is 0.0136-0.0140%, and the RSD value is 2.34-3.81%. Therefore, it is shown that the liquid chromatography detection method for moxifloxacin degradation impurity J provided in the present application has high detection accuracy and good repeatability, and can be used to detect the content of moxifloxacin degradation impurity J in moxifloxacin hydrochloride sodium chloride injection, so as to achieve effective quality control.

[0048] The test solution was detected by the method provided in Comparative Examples 1 and 2. The chromatographic peak of the moxifloxacin degradation impurity J in the obtained detection spectrum showed obvious irregularity, asymmetry and tail tailing, and the content of the moxifloxacin degradation impurity J in the detected test solution was 0.0125-0.0129%, and the RSD value was as high as 4.58-5.06%. Therefore, it is explained that when a buffer solution containing diethylamine and tetrabutylammonium hydrogen sulfate or a buffer solution containing sodium octane sulfonate and tetrabutylammonium hydrogen sulfate is used as the mobile phase A, the elution and separation effect of the moxifloxacin degradation impurity J is poor, and the accuracy and repeatability of the detection results are poor.

[0049] The test solution was detected by the method provided in Comparative Example 3. The chromatographic peak of the moxifloxacin degradation impurity J in the obtained detection spectrum had obvious tailing, and the baseline separation was difficult. The content of the moxifloxacin degradation impurity J in the detected test solution was 0.0130%, and the RSD value was as high as 6.03%. This indicates that when the isocratic elution method is used to separate and detect the moxifloxacin degradation impurity J, the accuracy and repeatability of the detection results are poor.

[0050] The method provided in Comparative Example 4 was used to detect the test solution. The symmetry of the chromatographic peak of the moxifloxacin degradation impurity J in the obtained detection spectrum was poor, and the content of the moxifloxacin degradation impurity J in the detected test solution was 0.0132%, and the RSD value was as high as 4.12%. This indicates that the mobile phase and mobile phase gradient elution procedure provided in Comparative Example 4 cannot achieve stable and accurate detection of the moxifloxacin degradation impurity J.

[0051] The test results of Example 1 and Comparative Examples 1-2 show that the content of the moxifloxacin degradation impurity J in the test solution obtained by the method of Example 1 is 0.0140%, and the RSD value is 2.54% (≤3.00%); while the content of the moxifloxacin degradation impurity J in the test solution obtained by the method of Comparative Examples 1-2 is 0.0125-0.0129%, and the RSD value is 4.58-5.06%. This shows that the buffer solution containing three solutes, sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate, is used as the mobile phase A in the present application, which can achieve sufficient elution and accurate separation of the moxifloxacin degradation impurity J, thereby achieving accurate detection of the moxifloxacin degradation impurity J in the sample.

[0052] The test results of Examples 1-11 show that the content of the moxifloxacin degradation impurity J in the test solution obtained by the methods of Examples 1, 3-4, 7 and 10 is 0.0139-0.0140%, and the RSD value is 2.34-2.85% (≤3.00%); while the content of the moxifloxacin degradation impurity J in the test solution obtained by the methods of Examples 2, 5-6 and 11 is 0.0136-0.0138%, and the RSD value is 3.23-3.81% (>3.00%). Therefore, it is explained that the present application further controls the content of each substance in the mobile phase A within the following range: the concentration of sodium octane sulfonate is 0.2-0.4g / L, the concentration of diethylamine is 0.4-0.6g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4-0.6g / L, and the accuracy and repeatability of the obtained detection method are better.

[0053] It can be seen from the test results of Example 1 and Comparative Examples 3-4 that the content of moxifloxacin degradation impurity J in the test solution obtained by the mobile phase elution procedure of Example 1 is 0.0139-0.0140%, and the RSD value is 2.34-2.85% (≤3.00%); while the content of moxifloxacin degradation impurity J in the test solution obtained by the detection method of Comparative Examples 3-4 is only 0.0130-0.0132%, and the RSD value is as high as 4.21-6.03%. Therefore, it is shown that the use of the mobile phase and gradient elution procedure provided by the present application can achieve efficient elution of moxifloxacin degradation impurity J, and then can achieve accurate detection of moxifloxacin degradation impurity J in the sample.

[0054] Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A liquid chromatography detection method for moxifloxacin degradation impurity J, characterized in that: The following steps are involved: Prepare reference solution, prepare test solution, and perform liquid chromatography detection; Liquid chromatography detection: The reference solution and the test solution are injected into the liquid chromatograph, and the mobile phase gradient elution method is used for separation and detection; the chromatographic column used is a chromatographic column filled with phenyl bonded silica gel; The mobile phase gradient elution process is as follows: at 0-10 min, mobile phase A is 100%, and mobile phase B is 0%; at 10-35 min, mobile phase A is linearly reduced to 72%, and mobile phase B is linearly increased to 28%; at 35-40 min, mobile phase A is 72%, and mobile phase B is 28%; at 40-45 min, mobile phase A is linearly increased to 100%, and mobile phase B is linearly reduced to 0%; at 45-50 min, mobile phase A is 100%, and mobile phase B is 0%; mobile phase A and mobile phase B are both expressed in volume percentages; The mobile phase A is a buffer solution containing sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate, and the mobile phase B is methanol.

2. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that, In the mobile phase A, the concentration of sodium octane sulfonate is 0.2-0.4 g / L, the concentration of diethylamine is 0.4-0.6 g / L, and the concentration of tetrabutylammonium hydrogen sulfate is 0.4-0.6 g / L.

3. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that, The preparation method of the mobile phase A is as follows: sodium octane sulfonate, diethylamine and tetrabutylammonium hydrogen sulfate are dissolved in a phosphate buffer to prepare the mobile phase A; in the phosphate buffer, the concentration of disodium hydrogen phosphate is 30 g / L, the concentration of phosphoric acid is 25 g / L, and the pH value of the phosphate buffer is adjusted to 5.6 by triethylamine.

4. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that: In the liquid chromatography detection, the flow rate of the mobile phase is 1.2-1.4 mL / min.

5. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that, In the liquid chromatography detection, the column temperature is 35-45°C.

6. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that: In the liquid chromatography detection, the detection wavelength is 293 nm.

7. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that: In the liquid chromatography detection, the chromatographic column is Kromasil 100-5-phenyl, 250mm×4.6mm, 5μm.

8. The liquid chromatography detection method for moxifloxacin degradation impurity J according to claim 1, characterized in that: The detection limit of the moxifloxacin degradation impurity J is 0.003 μg / mL, and the quantification limit is 0.01 μg / mL.

9. Application of the liquid chromatography detection method of moxifloxacin degradation impurity J as claimed in any one of claims 1 to 8 in the detection of moxifloxacin degradation impurity J in moxifloxacin hydrochloride and sodium chloride injection.

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