A method for determining ceftazidime polymer

Abstract

The present invention discloses a method for determining a ceftazidime polymer, and the method comprises the following steps: A method for determining a ceftazidime polymer, characterized in that the method comprises the following steps: 1) preparing a test solution of ceftazidime for injection; 2) preparing a reference solution; 3) determining: taking the test solution and the reference solution and injecting them into a liquid chromatograph respectively, and determining by reverse phase chromatography, wherein the mobile phase of the reverse phase chromatography contains mobile phase A and mobile phase B, mobile phase A is ammonium formate solution and / or ammonium acetate solution, and mobile phase B is acetonitrile. The chromatogram obtained by the determination method of the present invention has a stable baseline, can detect multiple polymer impurities of ceftazidime, and the separation degree of each impurity is good; the determination method of the present invention has good specificity and system applicability, and the repeatability, intermediate precision and durability of the determination method of the present invention are good; in addition, the test solution and the reference solution of the present invention have high stability.

Description

Technical Field

[0001] The invention relates to the field of ceftazidime detection, in particular to a method for determining a ceftazidime polymer. Background Art

[0002] Ceftazidime, i.e. (6R, 7R)-7-[[(2-amino-4-thiazolyl)-[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-3-methylpyridinium inner salt pentahydrate, is a third-generation broad-spectrum semisynthetic cephalosporin used for infections of the lower respiratory tract, skin and soft tissue, bones and joints, chest cavity, abdomen, genitourinary system and central nervous system caused by sensitive strains of Gram-negative bacteria, and is also used for sepsis.

[0003] Ceftazidime polymers are the main degradation products of antibiotic compounds. The current quality inspection method for ceftazidime polymers is the G-10 molecular exclusion method (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0514). The molecular exclusion method verifies the specificity of the G-10 molecular exclusion method for polymers. The polymer components determined by this method cannot represent the actual content of ceftazidime polymers in the product, and may be other small molecule impurities.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a quality detection method for ceftazidime polymers to achieve the purpose of improving the specificity, accuracy and sensitivity of the detection method; the detection method of the present invention can detect multiple polymer impurities of ceftazidime, and the separation degree of each impurity is good.

[0006] The basic concept of the technical solution adopted in the present invention is:

[0007] A method for determining a ceftazidime polymer comprises the following steps:

[0008] 1) preparing a test solution of ceftazidime for injection;

[0009] 2) preparing a reference solution;

[0010] 3) Determination

[0011] The test solution and the reference solution are respectively injected into a liquid chromatograph and determined by reverse phase chromatography, wherein the mobile phase of the reverse phase chromatography contains mobile phase A and mobile phase B, mobile phase A is ammonium formate solution and / or ammonium acetate solution, and mobile phase B is acetonitrile.

[0012] Furthermore, the concentration of the ammonium formate solution is 10 mmol / L, and the pH value of the ammonium formate solution is 4.0.

[0013] Furthermore, the preparation method of the mobile phase A is: adjusting the pH value of the ammonium formate solution to 4.0 with formic acid.

[0014] In the present invention, a chromatographic column Hypersil ODS-2 (250×4.6 mm, 5 μm) is used to separate ceftazidime impurities. According to the result analysis, in the chromatogram obtained by using the chromatographic column, the baseline is stable and the separation of ceftazidime impurities is good.

[0015] Furthermore, the chromatographic column used in the reverse phase chromatography method is Hypersil ODS-2 (250×4.6 mm, 5 μm).

[0016] In the present invention, the reverse phase chromatography adopts gradient elution to carry out elution, and the elution gradient is as follows:

[0017]

[0018] Further, the determination conditions of the reverse phase chromatography also include:

[0019] Flow rate: 1ml / min

[0020] Column temperature: 40°C

[0021] Wavelength: 254nm

[0022] Injection volume: 20 μl.

[0023] In the present invention, 20 μl of the test solution is injected into a liquid chromatograph, and the chromatogram is recorded. The retention time of the main peak of ceftazidime is about 11±2 min, the relative retention time of the polymer impurity is about 2.0-3.0, and there are 5 obvious polymer impurity peaks. Among them, a single polymer impurity shall not exceed 0.2%, and the total amount of polymer shall not exceed 0.5%.

[0024] Furthermore, in the step 1), preparing the test solution of ceftazidime for injection comprises: weighing ceftazidime for injection, and adding water to dissolve it to prepare the test solution.

[0025] Furthermore, the concentration of the test solution is 5 mg / mL.

[0026] Furthermore, in the step 2), preparing the reference solution includes: taking the test solution, diluting it with water, and preparing the reference solution.

[0027] Furthermore, in step 2), the volume ratio of the test solution to the reference solution is 1:100.

[0028] After adopting the above technical solution, the present invention has the following beneficial effects compared with the prior art:

[0029] (1) Specificity and system applicability of the assay method of the present invention

[0030] The blank of the invention has no interfering peaks; the relative retention time of the main peak of ceftazidime is RRT1.00, and there are polymer impurity peaks of RRT2.07, RRT2.11, RRT2.20, RRT2.36 and RRT2.47; the polymer impurity peaks and adjacent peaks can be effectively separated, and the separation degrees are all greater than 1.5; the determination method of the invention has good specificity and system applicability.

[0031] (2) Stability of test solution and reference solution

[0032] The test solution of the present invention is placed at room temperature for 8 hours, and the absolute value of the total change of the polymer impurity content is 0.05%, which is not more than 0.05%; the reference solution is observed at room temperature for 12 hours, and the change rate of the peak area is 3.16%, which is not more than 10.0%; the above results show that the test solution is stable when placed at room temperature for 8 hours; the reference solution is stable when placed at room temperature for 12 hours; that is, the test solution and the reference solution of the present invention have good stability.

[0033] (3) Precision - analytical repeatability

[0034] In the six test sample solutions of the present invention, the standard deviation coefficient RSD of the sum of the polymer impurity contents is 1.69%, which is less than 15.0%, and the determination method has good repeatability.

[0035] (4) Precision-Intermediate Precision

[0036] In the six method verification sample solutions of the present invention, the RSD of the sum of the polymer impurity contents was 3.10%, which was less than 15.0%, meeting the acceptance criteria, indicating that the intermediate precision met the requirements.

[0037] Different personnel tested the same uniform sample. The RSD of polymer impurity content in 12 test solutions was 0.00% and no more than 15.0%, indicating good precision.

[0038] (5) Linearity and range (LOQ ~ 40 μg / ml)

[0039] In the concentration range of 0.011 μg / mL to 42.488 μg / mL (LOQ to 800% limit concentration), the concentration of ceftazidime was linearly correlated with the peak area, y=0.8146x+0.0225, r=1, which was greater than 0.995 and met the acceptance criteria; the y-axis intercept deviation was 0.52%, which was less than 25% and met the regulations.

[0040] (6) Limit of quantification (LOQ) and limit of detection (LOD)

[0041] The LOQ concentration of ceftazidime for injection was 0.011 μg / mL; the RSD of the peak area for 6 consecutive injections was 5.21%, which was less than 10.0%; the average S / N value was 12.03, which was greater than 10; it met the requirements.

[0042] The LOD concentration of ceftazidime for injection is 0.005 μg / mL. The peak area RSD is 11.07%, less than 20.0%; the S / N average is 6.06, greater than 3, which meets the requirements.

[0043] (7) Durability

[0044] When there are slight changes in the measurement conditions (such as flow rate, different batches of chromatographic columns), the method system applicability meets the requirements, the absolute value of the change in the total polymer impurity content compared with normal conditions is less than 0.05%, and the durability meets the requirements.

[0045] The specific implementation modes of the present invention are further described in detail below in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The accompanying drawings are part of the present invention and are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention, but do not constitute an improper limitation of the present invention. Obviously, the drawings described below are only some embodiments. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work. In the accompanying drawings:

[0047] Figure 1 is the chromatogram obtained from Example 1 of the present invention;

[0048] Figure 2 is a chromatogram obtained from Test Example 1 of the present invention;

[0049] Figure 3 is the chromatogram obtained from Test Example 2 of the present invention;

[0050] Figure 4 is another chromatogram of Example 1 of the present invention;

[0051] Figure 5 is the chromatogram obtained in Test Example 4 of the present invention;

[0052] Figure 6 is a line graph of ceftazidime of the present invention;

[0053] Figure 7 The UV images of the compounds obtained in Example 2 of the present invention;

[0054] Figure 8 is the mass spectrum of polymer 1006;

[0055] Fig. 9 is the mass spectrum of polymer 1014;

[0056] Fig.10 is the mass spectrum of polymer 675;

[0057] Fig.11 is the mass spectrum of polymer 859;

[0058] Fig.12 is the mass spectrum of polymer 802.

[0059] It should be noted that these drawings and textual descriptions are not intended to limit the conceptual scope of the present invention in any way, but are intended to illustrate the concept of the present invention for those skilled in the art by referring to specific embodiments. DETAILED DESCRIPTION

[0060] Example 1

[0061] 1) Prepare the test solution:

[0062] Take ceftazidime for injection, weigh accurately, dissolve in water and quantitatively dilute to make a solution containing about 5 mg of ceftazidime per 1 ml;

[0063] 2) Preparation of reference solution:

[0064] Accurately measure 1 ml of the test solution, place it in a 100 ml volumetric flask, dilute to the mark with water, and shake well;

[0065] 3) Inject the test solution and reference solution into the liquid chromatograph and record the chromatogram;

[0066] Chromatographic conditions:

[0067] Instrument: Vanquish ultra-high performance liquid chromatograph

[0068] Chromatographic column: Hypersil ODS-2 (250×4.6mm, 5μm)

[0069] Mobile phase A: 10 mmol / L ammonium formate solution, pH adjusted to 4.0 with formic acid.

[0070] Mobile phase B: acetonitrile

[0071] Flow rate: 1ml / min

[0072] Column temperature: 40°C

[0073] Wavelength: 254nm

[0074] Injection volume: 20 μl

[0075] Test solution concentration: 5 mg / mL

[0076] Elution gradient:

[0077]

[0078] In this example, 20 μl of the test solution was injected into a liquid chromatograph and the chromatogram was recorded. Figure 1 As shown in the chromatogram, the retention time of the main peak of ceftazidime is about 11±2min, the relative retention time of the polymer impurity is about 2.0-3.0, and there are 5 obvious polymer impurity peaks. Taking the relative retention time of the main peak of ceftazidime as RRT1.00, the 5 obvious polymer impurity peaks are RRT2.07, RRT2.11, RRT2.20, RRT2.36, and RRT2.47, respectively. The polymer impurity peaks can be effectively separated from the adjacent peaks, and the resolution is greater than 1.5.

[0079] In the present invention, the reverse phase chromatography analysis method is optimized and can detect multiple polymer impurities of ceftazidime, and the separation degree of each impurity is good, which proves that the method specificity of analyzing ceftazidime polymer impurities by reverse phase chromatography is good.

[0080] Example 2

[0081] In this example, LC / MS method was used to analyze the impurities in the ceftazidime polymer, wherein the chromatographic conditions were those in Example 1, and the mass spectrometry conditions included:

[0082] Ion source parameters:

[0083]

[0084]

[0085] Scan parameters:

[0086]

[0087] The UV images of the compounds obtained by the above analysis methods in this example are as follows Figure 7 As shown by Figure 7 It can be seen that the analysis method of this embodiment can obtain five compounds, namely Unk-1, Unk-2, Unk-3, Unk-4 and Unk-5, among which Unk-1 represents polymer 1006, Unk-2 represents polymer 1014, Unk-3 represents polymer 675, Unk-4 represents polymer 859 and Unk-5 represents polymer 802.

[0088] Combination Figures 8 to 12The polymer structure information table of Unk-1, Unk-2, Unk-3, Unk-4 and Unk-5 is as follows:

[0089]

[0090]

[0091] Furthermore, the Unk-1 structure derivation and fragment information are as follows:

[0092]

[0093] According to the spectral analysis, 1006.19586 (M+H) is the quasi-molecular ion peak of the impurity. There is one and only one pyridine structure in the pyridine fragment structure of the ceftazidime structure. According to the molecular weight, the impurity is a dimer. It is speculated that the structure is a polymer of ceftazidime and its degradation products. The difference between this impurity and ceftazidime is 460, and 460 is the degradation product of ceftazidime in which the pyridine ring is replaced by a hydroxyl group after ring-opening and decarboxylation. The molecular weight accuracy and fragments support the structural inference.

[0094] The Unk-2 structure derivation and fragment information are as follows:

[0095]

[0096] According to the spectrum analysis, 1014.16522 (M+H) is the quasi-molecular ion peak of the impurity. There is only one pyridine structure in the pyridine fragment structure of the ceftazidime structure. According to the molecular weight, the impurity is a dimer. It is speculated that the structure is a polymer of ceftazidime and its degradation product. The molecular weight of 1014 and the ceftazidime dimer differ by one pyridine ring, so the impurity is a dimer directly connected to the ceftazidime amino group after ceftazidime loses the pyridine ring. The molecular weight accuracy and fragments support the structural inference. Unk-3 structure derivation and fragment information:

[0097]

[0098] According to the spectrum analysis, 675.09882 (M+H) is the quasi-molecular ion peak of the impurity. There is only one pyridine ring structure lost in the fragment, so the impurity is also the product of the polymerization of ceftazidime and its degradation product. The impurity has two carboxyl groups through fragment analysis, and the isotope abundance calculation shows that the impurity contains three sulfurs, so it is speculated that the ceftazidime degradation product is a structure formed by the β-lactam ring fusion and the hydrogenated thiazine ring opening after ceftazidime loses pyridine. The polymer impurity should be formed by the polymerization of ceftazidime and the unstable product. The molecular weight accuracy and fragments support the structural inference.

[0099] Unk-4 structure derivation and fragment information:

[0100]

[0101] According to the spectral analysis, 859.16010 (M+H) is the quasi-molecular ion peak of the impurity. Only one pyridine ring structure is lost in the fragment, so the impurity is also the product of the polymerization of ceftazidime and its degradation product. According to the nitrogen rule calculation, the impurity is speculated to be the product of the polymerization of ceftazidime and ceftazidime impurity G. The molecular weight accuracy and fragments both support the structural inference.

[0102] Unk-5 structure derivation and fragment information:

[0103]

[0104] According to the spectral analysis, 802.13806 (M+H) is the quasi-molecular ion peak of the impurity. Only one pyridine ring structure is lost in the fragment, so the impurity is also the product of the polymerization of ceftazidime and its degradation product. According to the nitrogen rule calculation, the impurity is speculated to be the product of the polymerization of ceftazidime and the side chain acid of ceftazidime degradation. The molecular weight accuracy and fragments support the structural inference.

[0105] Through RP-HPLC-MS analysis, a total of 5 polymer impurity peaks were resolved in the reversed-phase chromatography system. After optimization, the reversed-phase chromatography analysis method can detect multiple polymer impurities of ceftazidime, and the separation of each impurity is good, which proves that the reversed-phase chromatography method for analyzing ceftazidime polymer impurities has good specificity.

[0106] 1. Selection of determination method conditions

[0107] Test Example 1

[0108] The difference between the determination method of this test example and that of Example 1 is that the mobile phase A is 5 mmol / L ammonium acetate (1 ml of acetic acid is added), the mobile phase B is acetonitrile, and the chromatogram recorded is as follows Figure 2 shown.

[0109] Test Example 2

[0110] The difference between the determination method of this test example and that of Example 1 is that the mobile phase A is 0.1% formic acid, the mobile phase B is acetonitrile, and the chromatogram recorded is as follows: Figure 3 shown.

[0111] By analyzing Figures 2 to 4 It was found that when mobile phase A was 5mmol / L ammonium acetate (1ml of acetic acid was added) and 0.1% formic acid, the baseline fluctuated greatly and the separation of impurities after the main peak of ceftazidime was poor. These two conditions were not suitable as mobile phases; when mobile phase A was 10mmol / L ammonium formate (the pH was adjusted to 4.0 with formic acid), the separation of impurities after the main peak of ceftazidime was good, so 10mmol / L ammonium formate (the pH was adjusted to 4.0 with formic acid) was selected as mobile phase A.

[0112] Test Example 3

[0113] The difference between the determination method of this test example and that of Example 1 is that the chromatographic column used is Hypersil GOLDTM (250×4.6 mm, 5 μm), and the chromatogram recorded is as follows: Figure 5 shown.

[0114] By analyzing Figure 4 and Figure 5 It can be seen that different types of chromatographic columns have different effects on the separation of impurities. The chromatogram obtained by using the chromatographic column Hypersil ODS-2 (250×4.6 mm, 5 μm) of the present invention has a stable baseline and is better for the separation of ceftazidime impurities.

[0115] 2. Methodological validation:

[0116] 2.1. Specificity and system applicability of the assay method of the present invention

[0117] 1) Test method

[0118] Prepare and inject blank solution and test solution.

[0119] 2) The test results are shown in Table 1 below:

[0120] Table 1 (Specificity and system suitability test results table):

[0121]

[0122]

[0123] 3) Specificity and system suitability verification conclusion

[0124] There is no interference peak in the blank; the relative retention time of the main peak of ceftazidime is RRT1.00, and there are polymer impurity peaks RRT2.07, RRT2.11, RRT2.20, RRT2.36, and RRT2.47; the polymer impurity peaks and adjacent peaks can be effectively separated; the resolution is greater than 1.5. The specificity and system applicability meet the requirements.

[0125] 2.2 Stability of test solution and reference solution

[0126] 1) Test method

[0127] Prepare the ceftazidime injection test solution and control solution, place them at room temperature, and measure them at 0, 2, 4, 6, 8, 10, and 12 hours. Calculate the relative changes in the content of ceftazidime injection polymer impurities and the ceftazidime peak area of ​​the control solution at 0h. If the absolute value of the total change in the polymer impurity content in the test solution is ≤0.05%, and the change in the main peak area of ​​the control solution is ≤10.0%, the solution can be considered stable.

[0128] 2) The test results are shown in Table 2 below:

[0129] Table 2 (Solution stability (room temperature) results table):

[0130]

[0131]

[0132] 3) Solution stability verification conclusion

[0133] When the test solution was observed at room temperature for 8 hours, the absolute value of the change in the total polymer impurity content was 0.05%, not more than 0.05%; when the control solution was observed at room temperature for 12 hours, the change rate of the peak area was 3.16%, not more than 10.0%.

[0134] Therefore, the test solution of ceftazidime for injection is stable within 8 hours at room temperature; the control solution is stable within 12 hours at room temperature.

[0135] 2.3. Precision-analysis repeatability:

[0136] 1) Test method

[0137] Analyst 1 prepared 6 test sample solutions and injected them for analysis.

[0138] 2) The test results are shown in Table 3 below.

[0139] Table 3 (Repeatability results table):

[0140]

[0141]

[0142] 3) Repeatability Verification Conclusion

[0143] The RSD of the sum of the polymer impurity contents in the 6 test solutions was 1.69%, which was less than 15.0%. The repeatability of this analytical method met the requirements.

[0144] 2.4. Precision-Intermediate Precision

[0145] 1) Test method

[0146] Analyst 2 prepared 6 test sample solutions and injected them for analysis.

[0147] 2) The test results are shown in Table 4 below.

[0148] Table 4 (Repeatability results table):

[0149]

[0150] The comparison results are shown in Table 5:

[0151] Table 5:

[0152]

[0153] 3) Intermediate precision conclusion

[0154] Another analyst and another instrument tested 6 sample solutions for method validation under the same conditions. The RSD of the total polymer impurity content was 3.10%, which was no more than 15.0%, meeting the requirements, indicating that the intermediate precision met the requirements. The RSD of the polymer impurity content of 12 sample solutions measured by different personnel, different instruments, and different time conditions was 0%, indicating good precision.

[0155] 2.5 Linearity and range

[0156] 1) Test method

[0157] The linearity of the ceftazidime standard solution was evaluated by injecting samples in the concentration range from LOQ to 800% limit, and the solutions at different concentration levels were injected once each.

[0158] 2) The test results are shown in Table 6 below, and the line graph is as follows Figure 6 ;

[0159] Table 6 (Linearity results table):

[0160]

[0161]

[0162] 3) Linear verification conclusion

[0163] For ceftazidime solution in the concentration range of 0.011 μg / mL to 42.488 μg / mL, the linear equation of concentration and peak area is y=0.8146x+0.0225; the correlation coefficient r is 1, which is greater than 0.995; the y-axis intercept deviation is 0.52%, which is less than 25%, indicating that the linear relationship of ceftazidime solution in the above concentration range meets the requirements.

[0164] 2.6 Limit of quantification (LOQ) and limit of detection (LOD) tests

[0165] 1) Test method

[0166] Limit of quantitation: Adjust an appropriate low concentration solution, S / N (signal-to-noise ratio) ≥ 10, inject the sample 6 times at this concentration, and test and calculate the precision of S / N and peak area.

[0167] Detection limit: Adjust an appropriate low concentration solution, S / N ≥ 3, inject this concentration 6 times, and test and calculate the precision of S / N and peak area.

[0168] 2) The test results are shown in Tables 7 and 8 below;

[0169] Table 7 (quantitation limit results table):

[0170]

[0171] Table 8 (Detection limit results table):

[0172]

[0173] 3) Conclusions on verification of quantitative limit and detection limit

[0174] The LOQ concentration of ceftazidime for injection is 0.011 μg / mL. The RSD of the peak area of ​​6 consecutive injections is 5.21%, which is less than 10.0%; the average S / N is 12.03, which is greater than 10, which meets the requirements.

[0175] The LOD concentration of ceftazidime for injection is 0.005 μg / mL. The peak area RSD is 11.07%, less than 20.0%; the average S / N is 6.06, greater than 3. It meets the requirements.

[0176] 2.7 Durability test

[0177] 1) Test method

[0178] The tolerance of the measurement results to slight changes in the measurement parameters will be evaluated by changing the flow rate of the mobile phase and different batches of chromatographic columns of the same model. The system suitability is required to meet the requirements under each changed chromatographic condition parameter; the absolute value of the change in polymer impurity content is ≤0.05% compared with the method setting conditions.

[0179] 2) The test results are shown in Table 9 below:

[0180] Table 9: (Durability results table):

[0181]

[0182]

[0183] Normal conditions: chromatographic column A2020011, flow rate 1.0 ml / min.

[0184] 3) Durability Verification Conclusion

[0185] When there are slight changes in the measurement conditions (such as flow rate, different batches of chromatographic columns), the method system applicability meets the requirements, the absolute value of the change in the total polymer impurity content compared with normal conditions is less than 0.05%, and the durability meets the requirements.

[0186] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment, it is not used to limit the present invention. Any technician familiar with this patent can make some changes or modify the technical contents suggested above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the solution of the present invention.

Claims

1. A method for determining a ceftazidime polymer, characterized in that: The determination method comprises the following steps: 1) Weigh ceftazidime for injection and dissolve it in water to prepare a test solution. The concentration of the test solution is 5 mg / mL; 2) preparing a reference solution; 3) Determination; The test solution and the reference solution were respectively injected into a liquid chromatograph and determined by reverse phase chromatography, wherein the mobile phase of the reverse phase chromatography contained mobile phase A and mobile phase B, mobile phase A was an ammonium formate solution with a concentration of 10 mmol / L, the ammonium formate solution was adjusted to a pH value of 4.0 with formic acid, and mobile phase B was acetonitrile; The chromatographic column was Hypersil ODS-2, 250 × 4.6 mm, 5 μm; Flow rate: 1ml / min; Column temperature: 40°C; Wavelength: 254nm; Reverse phase chromatography uses gradient elution, and the elution gradient is as follows: The above method can be used to determine whether compounds Unk-1, Unk-2, Unk-3, Unk-4 and Unk-5 exist in the ceftazidime polymer. The compound structure information is as follows: 。 2. The method for determining a ceftazidime polymer according to claim 1, characterized in that: The determination conditions of reverse phase chromatography also include: Injection volume: 20 μl.

3. The method for determining a ceftazidime polymer according to claim 1, characterized in that: In the step 2), preparing the reference solution includes: taking the test solution and diluting it with water to prepare the reference solution.

4. The method for determining a ceftazidime polymer according to claim 3, characterized in that: In the step 2), the test solution is taken and diluted 100 times to prepare the reference solution.

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