Cefuroxime Axetil

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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C₂₀H₂₄N₄O₁₀S 510.47 

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 3-[[(aminocarbonyl)oxy]methyl]-7-[[2-furanyl(methoxyimino)acetyl]amino]-8-oxo-, 1- (acetyloxy)ethyl ester, [6R-[6α,7β(Z)]]-; 

(RS)-1-Hydroxyethyl (6R,7R)-7-[2-(2-furyl)glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, 72-(Z)-(O-methyloxime), 1-acetate 3-carbamate CAS RN®: 64544-07-6; UNII: Z49QDT0J8Z. 

1 DEFINITION 

Cefuroxime Axetil is a mixture of the diastereoisomers of cefuroxime axetil (C₂₀H₂₄N₄O₁₀S). It contains the equivalent of NLT 745 µg/mg and  

NMT 875 µg/mg of cefuroxime (C₁₆H₁₆N₄O₈S), calculated on the anhydrous basis. 

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K  : Meets the requirements B. The retention times 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 

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

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 0.2 mg/mL of USP Cefuroxime Axetil RS in Mobile phase 

Standard solution: 0.2 mg/mL of USP Cefuroxime Axetil RS in Mobile phase. Protect the solution from light, refrigerate, and use on the day prepared. 

Sample solution: 0.2 mg/mL of Cefuroxime Axetil 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 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—See Table 1 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 quantity, in µg/mg, of cefuroxime (C₁₆H₁₆N₄O₈S) in the portion of Cefuroxime Axetil taken: 

Result = (r_U/r_T) × (C_S/C_U) × P 

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) 

Acceptance criteria: 745–875 µg/mg on the anhydrous basis 

4 IMPURITIES 

Organic Impurities 

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

Reference solution: 2 µg/mL of USP Cefuroxime Axetil RS in Mobile phase. Protect the solution from light, refrigerate, and use on the day prepared. 

System suitability 

Samples: System suitability solution and Peak identification solution 

[Note—See Table 1 for relative retention times. Use the Peak identification solution to identify the locations of the cefuroxime axetil E isomers.] 

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 

Analysis 

Samples: Sample solution and Reference solution 

Calculate the percentage of each impurity in the portion of Cefuroxime Axetil 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 1. The reporting threshold is 0.05 times the sum of the responses of the two major peaks from the Reference solution. 

Table 1 

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

^b(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. 

^c(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. d The system may resolve two isomers. The limit is for the sum of the two isomers. 

^e(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. 

^f (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. 

^g The system may resolve three isomers. The limit is for the sum of the three isomers. 

^h(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}. 

5 SPECIFIC TESTS 

Crystallinity 〈695〉: Particles that do not show birefringence or exhibit extinction positions are amorphous, and particles that show birefringence and exhibit extinction positions are crystalline. 

Water Determination, Method I〈921〉: NMT 1.5% 

Diastereoisomer Ratio 

Solution A, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay. 

Analysis 

Sample: Sample solution 

Calculate the ratio of cefuroxime axetil diastereoisomer A to the sum of cefuroxime axetil diastereoisomers A and B: 

Result = r_A/r_T 

r_A = peak response of cefuroxime axetil diastereoisomer A  

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

Acceptance criteria: 0.48–0.55 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers. 

Labeling: Label it to indicate whether it is amorphous or crystalline. 

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. 

C₂₀H₂₄N₄O₁₀S      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. 

C₂₀H₂₄N₄O₁₀S      510.47