Cefuroxime Axetil Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Cefuroxime Axetil Tablets contain the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of cefuroxime (C₁₆H₁₆N₄O₈S).  

2 IDENTIFICATION 

A. The retention times of the peaks of cefuroxime axetil diastereoisomers A and B of the Sample solution correspond to those of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Solution A: 23 g/L of monobasic ammonium phosphate in water 

Mobile phase: Methanol and Solution A (38:62) 

Buffer: 23 g/L of monobasic ammonium phosphate in water, adjusted with phosphoric acid to a pH of 2.4 

System suitability stock solution: 0.1 mg/mL of USP Cefuroxime Axetil Delta-3 Isomers RS in methanol 

System suitability solution: 10 µg/mL of cefuroxime axetil delta-3 isomers from System suitability stock solution and 0.3 mg/mL of USP Cefuroxime Axetil RS in Mobile phase 

Standard solution: 0.3 mg/mL of cefuroxime axetil in Mobile phase. Protect the solution from light, refrigerate, and use on the day prepared.

Sample stock solution: Nominally 5 mg/mL of cefuroxime from finely powdered Tablets (NLT 5), prepared as follows. Transfer a suitable portion of the powder to a volumetric flask. Disperse in Buffer, using 5% of the nal volume. Sonicate if necessary. Add methanol to ll the volumetric flask to about half its capacity and shake by mechanical means for about 10 min. Dilute with methanol to volume, and filter.

Sample solution: Nominally 0.25 mg/mL of cefuroxime from the Sample stock solution in Mobile phase. Protect the solution from light, refrigerate, and use on the day prepared. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 278 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L13 

Flow rate: 1.2 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—See Table 4 for relative retention times.] 

Suitability requirements 

Resolution: NLT 1.5 between cefuroxime axetil diastereoisomers A and B; NLT 1.5 between cefuroxime axetil diastereoisomer A and cefuroxime axetil delta-3 isomers, System suitability solution 

Relative standard deviation: NMT 2.0% for the sum of cefuroxime axetil diastereoisomers A and B, Standard solution Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of cefuroxime (C₁₆H₁₆N₄O₈S) in the portion of Tablets taken: 

Result = (r_U/r_T) × (C_S/C_U) × P × F × 100 

r_U = sum of the peak responses of cefuroxime axetil diastereoisomers A and B from the Sample solution 

r_T = sum of the peak responses of cefuroxime axetil diastereoisomers A and B from the Standard solution  

C_S = concentration of USP Cefuroxime Axetil RS in the Standard solution (mg/mL) 

C_U = nominal concentration of cefuroxime in the Sample solution (mg/mL) 

P = potency of cefuroxime, on the anhydrous basis, in USP Cefuroxime Axetil RS (µg/mg) 

F = conversion factor, 0.001 mg/µg 

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Test 1 

Medium: 0.07 N hydrochloric acid; 900 mL 

Apparatus 2: 55 rpm 

Times: 15 and 45 min 

Standard solution: 10–20 µg/mL of cefuroxime from USP Cefuroxime Axetil RS in Medium 

Sample solution: Pass portions of the solution under test through a suitable filter and dilute with Medium, if necessary, to a concentration similar to that of the Standard solution. 

Instrumental conditions 

Mode: UV-Vis 

Analytical wavelength: 278 nm 

Blank: Medium 

Analysis 

Samples: Standard solution and Sample solution 

Determine the percentage (Q) of the labeled amount of cefuroxime (C₁₆H₁₆N₄O₈S) dissolved: 

Result = (A_U/A_S ) × C_S × V × (1/L) × P × F × 100 

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution 

C_S = concentration of USP Cefuroxime Axetil RS in the Standard solution (mg/mL) 

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

P = potency of cefuroxime, on the anhydrous basis, in USP Cefuroxime Axetil RS (µg/mg) 

F = conversion factor, 0.001 mg/µg 

Acceptance criteria 

For Tablets labeled to contain nominally 500 mg of cefuroxime: See Table 1.

For all other Tablets: See Table 2

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. 

Medium, Times, and Analysis: Proceed as directed in Test 1. 

Apparatus 2: 100 rpm 

Acceptance criteria: See Table 3. 

Table 3 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Organic Impurities 

Solution A, Mobile phase, Buffer, System suitability solution, and Sample solution: Proceed as directed in the Assay. Peak identification solution: 30 µg/mL of USP Cefuroxime Axetil E-Isomers RS in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 278 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L13 

Flow rate: 1.2 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Peak identification solution 

[Note—See Table 4 for the relative retention times. The Peak identification solution is used to identify the locations of the cefuroxime axetil E isomers.] 

Suitability requirements 

Resolution: NLT 1.5 between cefuroxime axetil diastereoisomer A and cefuroxime axetil delta-3 isomers, System suitability solution Analysis 

Sample: Sample solution 

Calculate the percentage of each impurity in the portion of Tablets taken: 

Result = (r_U/r_T) × 100 

r_U = peak response of each individual impurity from the Sample solution 

r_T = sum of the peak responses of cefuroxime axetil diastereoisomers A and B from the Sample solution Acceptance criteria: See Table 4. 

Table 4 

^aProcess impurities are controlled in the drug substance and are not to be reported here. They are not included in total impurities.

^b(Z)-2-(Furan-2-yl)-2-(methoxyimino)acetic acid. 

^c(6R,7R)-3-[(Carbamoyloxy)methyl]-7-[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

^d(Z)-N-((5aR,6R)-1,7-Dioxo-1,3,4,5a,6,7-hexahydroazeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl)-2-(furan-2-yl)-2-(methoxyimino)acetamide.

^e The system may resolve two isomers. The limit is for the sum of the two isomers. 

^f (1RS,6R,7R)-1-Acetoxyethyl 3-[(carbamoyloxy)methyl]-7-[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-3-ene-2-carboxylate. 

^g(1RS,6R,7R)-1-Acetoxyethyl 3-[(carbamoyloxy)methyl]-7-[(E)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylate. 

^h The system may resolve three isomers. 

ⁱ (6R,6′R,7R,7′R,Z)-Oxybis(ethane-1,1-diyl)bis{3-[(carbamoyloxy)methyl]-7-[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylate}. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature. 

Labeling: The labeling indicates whether the Tablets contain amorphous or crystalline Cefuroxime Axetil. If Tablets contain a mixture of amorphous and crystalline Cefuroxime Axetil, label to indicate the percentage of each contained therein. When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. 

USP Reference Standards 〈11〉 

USP Cefuroxime Axetil RS 

USP Cefuroxime Axetil Delta-3 Isomers RS 

(1RS,6R,7R)-1-Acetoxyethyl 3-[(carbamoyloxy)methyl]-7-[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3- ene-2-carboxylate. 

C₂₀H₂₂N₄O₁₀S      510.47 

USP Cefuroxime Axetil E-Isomers RS 

(1RS,6R,7R)-1-Acetoxyethyl 3-[(carbamoyloxy)methyl]-7-[(E)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylate. 

C₂₀H₂₂N₄O₁₀S       510.47