CN111948318A - Method for determining high-molecular polymer in cefuroxime axetil tablets - Google Patents
Method for determining high-molecular polymer in cefuroxime axetil tablets Download PDFInfo
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Abstract
The invention discloses a method for measuring a high molecular polymer in a cefuroxime axetil tablet, which comprises the following steps: the chromatographic conditions comprise a high-performance gel chromatographic column, a detector is UV, and a mobile phase is an N, N-dimethylformamide solution of 0.03 mol/L lithium halide containing unit alcohol with 3-8 carbon atoms in 25-35%. The method has better solution stability, can effectively prevent the degradation of the components to be detected of the cefuroxime axetil, and ensures the stability of the sample, thereby more accurately controlling the high molecular polymer in the cefuroxime axetil tablets, ensuring the product quality, preventing the anaphylactic reaction caused by the polymer, and better ensuring the safe medication of patients.
Description
Technical Field
The invention relates to the technical field of analysis, and particularly relates to a detection method for determining a high-molecular polymer in a cefuroxime axetil tablet.
Background
Cefuroxime axetil is a beta-lactam antibiotic, is one of the clinically common medicaments, and has the most common adverse reaction in clinic, namely immediate anaphylaxis. The research results at present reveal that the allergen inducing the allergic reaction is not the antibiotic per se but the existing high molecular polymer, so that the medical industry of various countries researches on the existing high molecular polymer. In order to seek better detection effect, chromatographic columns and fillers thereof aiming at the separation of high molecular polymers in beta-lactam antibiotics are emerging continuously. However, people mainly focus on the separation effect, the tailing of the peak shape, the repeatability of column packing, the analysis time and the like of the chromatographic column. The beta-lactam antibiotic solution is unstable and cannot be stored for a long time, so that the decomposition phenomenon of the sample can be caused by the long-term storage. The existing method has not attracted attention to the stability and the method applicability of the object to be detected.
Disclosure of Invention
The invention aims to establish a method for determining a high-molecular polymer in a cefuroxime axetil tablet, which has better solution stability, can effectively prevent the degradation of components to be detected of cefuroxime axetil and ensure the stability of a sample, thereby better controlling the high-molecular polymer in the cefuroxime axetil, ensuring the product quality, preventing anaphylactic reaction caused by the polymer and better ensuring the safe medication of patients.
The technical scheme of the invention is that the method for measuring the high molecular polymer in the cefuroxime axetil tablet comprises the following steps:
the chromatographic column is as follows: tskgel g2000Hhr (7.8 mml.d. × 30 cm);
chromatographic conditions are as follows: detection wavelength: 277 nm; column temperature: 30 ℃; sample introduction amount: 20 mu l; flow rate: 0.33 ml/min; mobile phase: 0.03 mol/L lithium bromide in 30% N-propanol in N, N-dimethylformamide.
Preparing a test solution: precisely weighing tablet powder equivalent to 20mg of cefuroxime axetil, placing the tablet powder in a 20ml measuring flask, and adding a mobile phase to a constant volume to a scale to obtain a sample solution;
preparation of control solution: precisely measuring 1ml of the test solution, placing the test solution in a 100ml measuring flask, diluting the test solution to a scale with a mobile phase, and shaking up to obtain a control solution;
preparation of a blank solution: a mobile phase;
calculating linear regression equation of the concentration value of the reference solution and the corresponding peak area value, wherein the correlation coefficient should not be less than 0.99, the reference solution has symmetrical peak shape, the theoretical plate number is more than 2000 based on cefuroxime axetil, and the polymer in the cefuroxime axetil tablet should not exceed 0.5%.
Description of the drawings: FIG. 1 is a system suitability chromatogram;
FIG. 2 is a linear regression chart of cefuroxime axetil.
The present invention will be described in further detail below by way of examples, but it should not be construed that the scope of the subject matter of the present invention is limited to the following examples. It is intended that all such alterations and modifications that come within the spirit and scope of the invention are desired to be embraced therein without departing from the spirit and scope of the invention as defined by the appended claims.
EXAMPLE 1 selection of solvent
Instruments and reagents
The instrument comprises the following steps: a water bath kettle and a balance;
reagent: n, N-dimethylformamide, methanol, ethanol, N-propanol, isopropanol, N-butanol, N-pentanol, N-hexanol, N-octanol and water.
Selection of a solvent:
10ml of N, N-dimethylformamide is added with 20mg of cefuroxime axetil tablet powder, and the mixture is kept warm in a water bath at 30 ℃ and shaken, so that the sample can be completely dissolved;
10ml of methanol is added into 20mg of cefuroxime axetil tablet powder, and the mixture is kept warm in water bath at 30 ℃ and shaken, so that the sample can be completely dissolved;
10ml of ethanol is added into 20mg of cefuroxime axetil tablet powder, and the mixture is subjected to heat preservation and shaking in water bath at the temperature of 30 ℃, so that a sample can be completely dissolved;
10ml of n-propanol, 20mg of cefuroxime axetil tablet powder is added, and the mixture is subjected to heat preservation and shaking in a water bath at the temperature of 30 ℃ so that a sample can be completely dissolved;
adding 10ml of isopropanol into 20mg of cefuroxime axetil tablet powder, and shaking in a water bath at 30 ℃ to ensure that the sample can be completely dissolved;
10ml of n-butyl alcohol is added into 20mg of cefuroxime axetil tablet powder, and the mixture is kept warm in water bath at 30 ℃ and shaken to completely dissolve the sample;
10ml of n-amyl alcohol, 20mg of cefuroxime axetil tablet powder is added, and the sample can be completely dissolved by shaking in a water bath at the temperature of 30 ℃;
adding 10ml of hexanol, adding 20mg of cefuroxime axetil tablet powder, and shaking in a water bath at 30 ℃ to ensure that the sample can be completely dissolved;
10ml of n-octanol, 20mg of cefuroxime axetil powder is added, and the sample can be completely dissolved by shaking in a water bath at the temperature of 30 ℃;
10ml of water, 20mg of cefuroxime axetil tablet powder was added, and the mixture was shaken in a water bath at 30 ℃ while maintaining the temperature, whereby the sample was not completely dissolved.
And (4) conclusion: under the condition of water bath heat preservation and shaking at the temperature of 30 ℃, the solubility of cefuroxime axetil in N, N-dimethylformamide, methanol, ethanol, N-propanol, isopropanol, N-butanol, N-pentanol, N-hexanol and N-octanol solvents can meet the requirement, and the cefuroxime axetil can not meet the requirement in water.
EXAMPLE 2 selection of absorption wavelength
10ml of N, N-dimethylformamide, 20mg of cefuroxime axetil tablet powder was added, and the maximum absorption wavelength was measured with air as a reference;
10ml of methanol, 20mg of cefuroxime axetil tablet powder is added, and the maximum absorption wavelength is measured by taking air as a reference;
ethanol 10ml, adding 20mg of cefuroxime axetil tablet powder, and measuring the maximum absorption wavelength by taking air as a reference;
10ml of n-propanol, 20mg of cefuroxime axetil tablet powder was added, and the maximum absorption wavelength was measured with air as a reference;
10ml of isopropanol, adding 20mg of cefuroxime axetil tablet powder, and measuring the maximum absorption wavelength by taking air as a reference;
adding 10ml of n-butanol into 20mg of cefuroxime axetil tablet powder, and measuring the maximum absorption wavelength by taking air as a reference;
n-amyl alcohol 10ml, adding 20mg of cefuroxime axetil tablet powder, and measuring the maximum absorption wavelength by taking air as a reference;
n-hexanol 10ml, adding 20mg of cefuroxime axetil tablet powder, and measuring the maximum absorption wavelength by taking air as a reference;
10ml of n-octanol, 20mg of cefuroxime axetil powder was added, and the maximum absorption wavelength was measured with air as a reference.
And (4) conclusion: the maximum absorption wavelength is within the range of 275-280nm, the absorption value of n-octanol at the same concentration is the lowest, the background absorption of the polyhydric alcohol above the n-octanol is increased, and the detection sensitivity is reduced.
Example 3 testing of solution stability
Detection wavelength: 280nm
Column temperature: 30 deg.C
Sample introduction amount: 20 mu l
Flow rate: 0.33ml/min
Mobile phase: 0.03 mol/L lithium bromide in N, N-dimethylformamide
A chromatographic column: TSKgelG2000Hhr (7.8 mml.D.. times.30 cm)
Sample preparation:
10ml of N, N-dimethylformamide, and 20mg of cefuroxime axetil tablet powder;
10ml of methanol, and 20mg of cefuroxime axetil tablet powder is added;
10ml of ethanol, and 20mg of cefuroxime axetil tablet powder is added;
10ml of n-propanol, 20mg of cefuroxime axetil tablet powder was added;
10ml of isopropanol, and 20mg of cefuroxime axetil tablet powder is added;
10ml of n-butanol, and 20mg of cefuroxime axetil tablet powder;
10ml of n-amyl alcohol, and 20mg of cefuroxime axetil tablet powder is added;
n-hexanol 10ml, 20mg of cefuroxime axetil tablet powder was added;
10ml of n-octanol, 20mg of cefuroxime axetil tablet powder is added;
10ml of mobile phase, 20mg of cefuroxime axetil tablet powder was added.
And taking the samples to perform detection at 0h, 3h, 6h, 9h, 12h, 15h, 18h, 21h and 24h respectively.
As a result: the peak area RSD of 1mg/ml cefuroxime axetil N, N-dimethylformamide solution in 24h is 10.8%, and the peak area RSD in 3h is 4.6%; the RSD of the 1mg/ml cefuroxime axetil methanol solution is 9.8% in the peak area within 24h and 4.9% in the peak area within 6 h; the RSD of the 1mg/ml cefuroxime axetil ethanol solution is 7.8 percent in the peak area within 24 hours and 4.3 percent in the peak area within 12 hours; the peak area RSD of the 1mg/ml cefuroxime axetil-n-propanol solution in 24h is 4.3%; the peak area RSD of the 1mg/ml cefuroxime axetil isopropanol solution in 24h is 4.1%; the peak area RSD of 1mg/ml cefuroxime axetil n-butanol solution in 24h is 3.5%; the peak area RSD of the 1mg/ml cefuroxime axetil-n-pentanol solution in 24h is 3.2%; the peak area RSD of the 1mg/ml cefuroxime axetil n-hexanol solution in 24h is 3.3 percent; the peak area RSD of the 1mg/ml cefuroxime axetil-n-octanol solution in 24 hours is 3.8%; the RSD of the 1mg/ml cefuroxime axetil mobile phase solution was 10.4% in 24h and 4.1% in 3 h.
When the peak shape of the chromatographic peak is inspected, the number of theoretical plates for dissolving the N, N-dimethylformamide and the mobile phase is more than 20000, and the tailing factor is less than 1.5. The theoretical plate number of the methanol, the ethanol, the n-propanol, the isopropanol, the n-butanol, the n-pentanol, the n-hexanol and the n-octanol dissolved is less than 20000, and the tailing factor is more than 1.5.
And (4) conclusion: the cefuroxime axetil sample has good solution stability in n-propanol, isopropanol, n-butanol, n-pentanol, n-hexanol and n-octanol within 24 hours, and can meet the detection requirement. The cefuroxime axetil samples were stable in N, N-dimethylformamide and the mobile phase for 3h, the cefuroxime axetil samples were stable in methanol for 6h, and the cefuroxime axetil samples were stable in ethanol for 12 h.
The separation effect of the N, N-dimethylformamide and the cefuroxime axetil dissolved in the mobile phase is good.
Example 4 selection of solvent
Chromatographic conditions are as follows: detection wavelength: 280nm
Column temperature: 30 deg.C
Sample introduction amount: 20 mu l
Flow rate: 0.33ml/min
Mobile phase: 0.03 mol/L lithium bromide in N, N-dimethylformamide
A chromatographic column: TSKgelG2000Hhr (7.8 mml.D.. times.30 cm)
Sample preparation:
10ml of 10% N-propanol solution in N, N-dimethylformamide, and 20mg of cefuroxime axetil tablet powder;
10ml of 30% N-propanol N, N-dimethylformamide solution, and 20mg of cefuroxime axetil tablet powder;
10ml of N, N-dimethylformamide solution of 50% N-propanol, 20mg of cefuroxime axetil tablet powder was added;
10ml of N, N-dimethylformamide solution of 70% N-propanol, 20mg of cefuroxime axetil tablet powder was added;
10ml of a 90% N-propanol solution in N, N-dimethylformamide was added to 20mg of cefuroxime axetil tablet powder.
And taking the samples to carry out sample injection detection for 0h, 3h, 6h, 9h, 12h, 15h, 18h, 21h and 24h respectively.
As a result: the peak area RSD of the 1mg/ml cefuroxime axetil 10% N-propanol N, N-dimethylformamide solution in 24 hours is 4.6%; the peak area RSD in 24h of 1mg/ml cefuroxime axetil 30% N-propanol in N, N-dimethylformamide is 3.8%; the peak area RSD of the 1mg/ml cefuroxime axetil solution in N, N-dimethylformamide with 50% N-propanol in 24h is 3.4%; the peak area RSD of the 1mg/ml cefuroxime axetil 70% N-propanol N, N-dimethylformamide solution in 24h is 3.1%; the peak area RSD of a 1mg/ml solution of cefuroxime axetil in N, N-dimethylformamide with 90% N-propanol was 3.2% in 24 hours.
When the peak shape of the chromatographic peak is inspected, the number of theoretical plates dissolved in the N, N-dimethylformamide solution of 90% of N-propanol is less than 20000, and the tailing factor is more than 1.5. The theoretical plate number of the N, N-dimethylformamide solution of 70% of N-propanol, the N, N-dimethylformamide solution of 50% of N-propanol, the N, N-dimethylformamide solution of 30% of N-propanol and the N, N-dimethylformamide solution of 10% of N-propanol is more than 20000, and the tailing factor is less than 1.5.
And (4) conclusion: the solution containing 10 to 90 percent of N, N-dimethylformamide of N-propanol is stable in 24 hours when cefuroxime axetil is dissolved.
The solution contains 10 to 70 percent of N, N-dimethylformamide of normal propyl alcohol, and has good separation effect of dissolving cefuroxime axetil.
EXAMPLE 5 optimization of the Mobile phase
Chromatographic conditions are as follows: detection wavelength: 280nm
Column temperature: 30 deg.C
Sample introduction amount: 20 mu l
Flow rate: 0.33ml/min
A chromatographic column: TSKgelG2000Hhr (7.8 mml.D.. times.30 cm)
Preparing a stock solution: a10 ml solution of 50% N-propanol in N, N-dimethylformamide was added to a 10mg sample of cefuroxime axetil as a stock solution.
Preparing a mobile phase: mobile phase 1: 0.03 mol/L lithium bromide in N, N-dimethylformamide solution;
mobile phase 2: 0.03 mol/L lithium bromide in 10% N-propanol in N, N-dimethylformamide;
mobile phase 3: 0.03 mol/L lithium bromide in 20% N-propanol in N, N-dimethylformamide;
mobile phase 4: 0.03 mol/L lithium bromide in 30% N-propanol in N, N-dimethylformamide;
mobile phase 5: 0.03 mol/L lithium chloride in 30% N-propanol in N, N-dimethylformamide.
And respectively taking the lowest detection limit of the mobile phase test sample.
As a result: the detection limit of mobile phase 1 is 2.5. mu.g/ml, that of mobile phase 2 is 1.7. mu.g/ml, that of mobile phase 3 is 1.2. mu.g/ml, that of mobile phase 4 is 0.5. mu.g/ml, and that of mobile phase 5 is 0.8. mu.g/ml.
And (4) conclusion: the detection limit of the mobile phase 4 is 1/5 of the mobile phase 1, and the sensitivity is improved by more than five times.
EXAMPLE 6 optimization of detection wavelength
Chromatographic conditions are as follows: detection wavelength: 275 ℃ C. 280nm
Column temperature: 30 deg.C
Sample introduction amount: 20 mu l
Flow rate: 0.33ml/min
A chromatographic column: TSKgelG2000Hhr (7.8 mml.D.. times.30 cm)
Mobile phase 0.03 mol/L lithium bromide in 30% N-propanol solution in N, N-dimethylformamide
Preparing a stock solution: a10 ml solution of 50% N-propanol in N, N-dimethylformamide was added to a 10mg sample of cefuroxime axetil as a stock solution.
The samples were detected at detection wavelengths of 275nm, 277nm, and 280nm, respectively.
As a result: the detection limit at 275nm is 0.7. mu.g/ml, the detection limit at 277nm is 0.4. mu.g/ml, and the detection limit at 280nm is 0.5. mu.g/ml
And (4) conclusion: the sensitivity is optimal at a detection wavelength of 277 nm.
Specificity of the method of example 7:
chromatographic conditions are as follows: detection wavelength: 277nm
Column temperature: 30 deg.C
Sample introduction amount: 20 mu l
Flow rate: 0.33ml/min
A chromatographic column: TSKgelG2000Hhr (7.8 mml.D.. times.30 cm)
Mobile phase 0.03 mol/L lithium bromide in 30% N-propanol solution in N, N-dimethylformamide
Precisely weighing cefuroxime axetil, cefuroxime and delta320mg of each of the isomer, the E isomer and the cefuroxime axetil dimer is put in a 20ml measuring flask, and the mobile phase is added to the constant volume to reach the scale to be used as a test solution;
characterization of each component: and taking 20 mul of sample introduction, respectively introducing samples, and recording a chromatogram. The retention time of each solvent peak is shown in table 1.
TABLE 1 Retention time of the solvents
And (4) conclusion: under the conditions of this method, since the separation degree of the cefuroxime axetil dimer from other components is greater than 1.5, the adjacent peaks can be completely separated.
Example 8 sample introduction precision detection
The chromatographic conditions were the same as in example 7.
Preparing a test solution: precisely weighing 20mg of cefuroxime axetil, putting the cefuroxime axetil into a 20ml measuring flask, and adding a mobile phase to a constant volume to a scale to obtain a sample solution;
preparation of a reference solution: precisely measuring 1ml of the test solution, placing in a 100ml measuring flask, diluting to scale with mobile phase, and shaking to obtain control solution.
TABLE 2 precision test
And (4) conclusion: the test shows that the precision of the chromatographic system is good.
Example 9 linear relationship examination:
the chromatographic conditions were the same as in example 7.
Preparing a test solution: precisely weighing 20.4mg of cefuroxime axetil, placing into a 20ml measuring flask, and adding mobile phase to a constant volume to obtain a sample solution.
Linear solution preparation:
precisely measuring 1ml of the test solution, placing the test solution in a 100ml measuring flask, diluting the test solution to a scale with a mobile phase, and shaking up to obtain a 100% solution.
Taking 8ml of 100% solution, placing the 100% solution in a 10ml measuring flask, diluting the solution to a scale with a mobile phase, and shaking up to obtain 80% solution;
taking 6ml of 100% solution, placing in a 10ml measuring flask, diluting to scale with mobile phase, and shaking up to obtain 60% solution;
taking 4ml of 100% solution, placing in a 10ml measuring flask, diluting to scale with mobile phase, and shaking up to obtain 40% solution;
taking 2ml of 100% solution, placing in a 10ml measuring flask, diluting to scale with mobile phase, and shaking up to obtain 20% solution;
taking 1ml of 100% solution, placing in a 10ml measuring flask, diluting to scale with mobile phase, and shaking up to obtain 10% solution;
taking 0.5ml of 100% solution, placing the solution in a 10ml measuring flask, diluting the solution to the scale with the mobile phase, and shaking up to obtain a sensitivity solution.
TABLE 3 Linear regression data for cefuroxime axetil
Regression equation y = 1.2940 x-0.0270 for cefuroxime axetil, R = 0.9998
And (4) conclusion: the results show that the concentration of cefuroxime axetil is 0.5-10 mug/ml respectively; the sample injection concentration and the peak area value have good linear relation in the range.
EXAMPLE 10 quantitative limits
The chromatographic conditions were as in example 7, calculated according to the formula LOQ =10 XSD/S, (S: the slope of the calibration curve, SD: the standard deviation of the y-intercept of the standard curve). The quantitative limit concentration of cefuroxime axetil was calculated from the linear regression data to be 0.5 mug/ml. Cefuroxime axetil was diluted to the above concentration and injected, and the results of the chromatogram were verified and recorded as shown in table 4.
TABLE 4 quantitative limits
Example 11 repeatability test:
the chromatographic conditions were the same as in example 7, 6 samples of the same lot were measured to determine the relative standard deviation, and the test results showed that the method had good reproducibility, and the results are shown in Table 5.
TABLE 5 results of the repeatability tests
And (4) conclusion: the test result shows that the method has good reproducibility.
Example 12 solution stability
The chromatographic conditions were the same as in example 7, and a test solution and a control solution were prepared
Preparing a test solution: precisely weighing 20mg of cefuroxime axetil, putting the cefuroxime axetil into a 20ml measuring flask, and adding a mobile phase to a constant volume to a scale to obtain a sample solution;
preparation of a reference solution: precisely measuring 1ml of the test solution, placing in a 100ml measuring flask, diluting to scale with mobile phase, and shaking to obtain control solution.
Injecting samples for 0h, 2h, 4h, 6h, 8h, 10h and 12h respectively at room temperature, and injecting 1 needle of 1% self-contrast solution and 1 needle of sample solution respectively. The results are shown in tables 6 and 7.
TABLE 6 Main peaks of control solutions
TABLE 7 Main peak of test solution
The conclusion is that the test result shows that the solution stability of the method is good.
EXAMPLE 13 variation of the proportion of the mobile phase in durability
The chromatographic conditions were the same as in example 7, and the following mobile phases were prepared in different n-propanol ratios:
mobile phase 1: 0.03 mol/L lithium bromide in 25% N-propanol in N, N-dimethylformamide
Mobile phase 2: 0.03 mol/L lithium bromide in 30% N-propanol in N, N-dimethylformamide
Mobile phase 3: 0.03 mol/L lithium bromide in 35% N-propanol in N, N-dimethylformamide
TABLE 8 comparison table of temperature variation test results of detectors
And (4) conclusion: the required separation was achieved as determined under the chromatographic conditions described above, and it was found that variations in the proportion of the durable mobile phase from 25% to 35% had no effect on the separation.
EXAMPLE 14 variation in durability flow Rate
The chromatographic conditions were as in example 7, with the flow rates being varied as follows: flow rate variation 1: 0.30ml/min, flow rate variation 1: 0.36ml/min, original flow rate: 0.33ml/min, and the test results are shown in Table 9.
TABLE 9 flow Rate Change test results comparison table
And (4) conclusion: the required separation effect can be achieved by measuring under the chromatographic conditions, and the change of the chromatographic conditions within the flow rate of 0.30 ml/min-0.36 ml/min has no influence on the separation.
EXAMPLE 15 durability column temperature Change
The chromatographic conditions were the same as in example 7, the column temperature was varied to: column temperature change 1: 25 ℃ and column temperature change of 2: 35 ℃ original column temperature: the results of the measurements at 30 ℃ are shown in Table 10.
TABLE 10 comparative table of column temperature change test results
And (4) conclusion: the required separation effect can be achieved by measuring under the chromatographic conditions, and the change of the chromatographic conditions of the initial column temperature within the range of 25-35 ℃ has no influence on the separation.
EXAMPLE 16 durability detection of wavelength Change
The chromatographic conditions were the same as in example 7, with the detector wavelength being varied as: detection wavelength change 1: 275nm, detection wavelength variation 2: 280nm, original detection wavelength: 277nm, and the test results are shown in Table 11.
TABLE 11 comparison table of column temperature variation test results
And (4) conclusion: the required separation effect can be achieved by measuring under the chromatographic conditions, and the change of the chromatographic conditions of the initial column temperature within the range of 65-75 ℃ has no influence on the separation of the cefuroxime axetil.
EXAMPLE 17 variation of the composition of the durable Mobile phase
The chromatographic conditions were the same as in example 7, the mobile phase composition was varied:
mobile phase 1: 0.03 mol/L lithium bromide in 30% N-propanol in N, N-dimethylformamide
Mobile phase 2: 0.03 mol/L lithium bromide in 30% isopropanol N, N-dimethylformamide
Mobile phase 1: 0.03 mol/L lithium bromide in 30% N-octanol solution in N, N-dimethylformamide
Mobile phase 1: 0.03 mol/L lithium bromide in N, N-dimethyl formamide solution of 30% N-butanol
The test results are shown in Table 12.
TABLE 12 comparison of mobile phase composition change test results
And (4) conclusion: the required separation effect can be achieved by the determination under the chromatographic conditions, and the separation of cefuroxime axetil is not influenced by the change of the chromatographic conditions of the mobile phase components.
Example 18 Multi-batch assay
The chromatographic conditions were the same as in example 7.
Blank solution: mobile phase
Preparing a test solution: precisely weighing tablet powder equivalent to 20mg of cefuroxime axetil, placing the tablet powder in a 20ml measuring flask, and adding a mobile phase to a constant volume to a scale to obtain a sample solution;
preparation of a reference solution: precisely measuring 1ml of the test solution, placing in a 100ml measuring flask, diluting to scale with mobile phase, and shaking to obtain control solution.
Sensitivity solution: taking 1ml of the control solution, placing the control solution in a 20ml measuring flask, diluting the control solution to the scale with the mobile phase, and shaking up.
Raw material sample: 180701,180702,180703, precisely weighing the above batch number 20mg, placing in a 20ml volumetric flask, adding mobile phase to constant volume to scale, and shaking up.
Sampling: blank solution sample injection 1 needle, sensitivity solution sample injection 1 needle, contrast solution sample injection 6 needles, sample injection 1 needle for sample solution and contrast solution respectively. The test results are shown in Table 13.
TABLE 13 results of multiple assays
And (4) conclusion: the method has good measurement results.
Claims (5)
1. The method for determining the high molecular polymer in the cefuroxime axetil tablet is characterized by comprising the following steps of:
the chromatographic column is as follows: a high performance gel chromatography column;
chromatographic conditions are as follows: detection wavelength: 275-280 nm; column temperature: 25-35 ℃; sample introduction amount: 20 mu l; flow rate: 0.30-0.36 ml/min; mobile phase: 0.03 mol/L of lithium halide in 25-35% of N, N-dimethylformamide solution containing 3-8 carbon atoms of monohydric alcohol;
preparing a test solution: precisely weighing tablet powder equivalent to 20mg of cefuroxime axetil, placing the tablet powder into a 20ml measuring flask, and adding a mobile phase or a mobile phase without lithium halide to a constant volume to obtain a sample solution;
preparation of control solution: precisely measuring 1ml of the test solution, placing the test solution in a 100ml measuring flask, diluting the test solution to a scale with a mobile phase or a mobile phase without lithium halide, and shaking up to obtain a control solution;
preparation of a blank solution: a mobile phase or a mobile phase without lithium halide;
calculating a linear regression equation of the concentration value of the reference solution and the corresponding peak area value, wherein the correlation coefficient should not be less than 0.99, the reference solution has symmetrical peak shape, the theoretical plate number is more than 2000 based on the cefuroxime axetil, and the polymer in the cefuroxime axetil tablet should not exceed 0.5%.
2. The method for determining the high molecular weight polymer in cefuroxime axetil tablets as claimed in claim 1, wherein:
a chromatographic column: TSKgelG2000 Hhr; mobile phase: 0.03 mol/L of lithium bromide or lithium chloride in 25-35% N, N-dimethylformamide of N-propanol or N-butanol or N-octanol or isopropanol.
3. The method for determining the high molecular weight polymer in cefuroxime axetil tablets as claimed in claim 1, wherein:
a chromatographic column: TSKgelG2000Hhr 7.8mml.D. times.30 cm; detection wavelength: 277 nm; column temperature: 30 ℃; sample introduction amount: 20 mu l; flow rate: 0.33 ml/min; mobile phase: 0.03 mol/L lithium bromide in 30% N-propanol in N, N-dimethylformamide.
4. The method for determining the high molecular weight polymer in cefuroxime axetil tablets as claimed in claim 1, wherein:
the chromatographic column is as follows: TSKgelG2000Hhr 7.8mml.D. times.30 cm; detection wavelength: 275 nm; column temperature: 25 ℃; sample introduction amount: 20 mu l; flow rate: 0.30 ml/min; mobile phase: 0.03 mol/L lithium bromide in 25% N-propanol in N, N-dimethylformamide.
5. The method for determining the high molecular weight polymer in cefuroxime axetil tablets as claimed in claim 1, wherein:
the chromatographic column is as follows: TSKgelG2000Hhr 7.8mml.D. times.30 cm; detection wavelength: 280 nm; column temperature: 35 ℃; sample introduction amount: 20 mu l; flow rate: 0.36 ml/min; mobile phase: 0.03 mol/L lithium bromide in 35% N-propanol in N, N-dimethylformamide.
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| CN104950053A (en) * | 2015-07-15 | 2015-09-30 | 江苏正大清江制药有限公司 | Method for measuring content of impurities in cefuroxime axetil tablet through high performance liquid chromatography |
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