Cefoxitin Sodium

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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C₁₆H₁₆N₃NaO₇S₂.   449.43

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 3-[[(aminocarbonyl)oxy]methyl]-7-methoxy-8-oxo-7-[(2-thienylacetyl)amino]-, sodium salt (6R-cis)-;

Sodium (6R,7S)-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate carbamate (ester) CAS RN®: 33564-30-6; UNII: Q68050H03T.

1 DEFINITION 

Cefoxitin Injection contains the equivalent of NLT 927 μg/mg and NMT 970 μg/mg of cefoxitin (C₁₆H₁₇N₃O₇S₂), corresponding to NLT 97.5% and NMT 102.0% of cefoxitin sodium (C₁₆H₁₆N₃O₇S₂), calculated on the anhydrous and acetone- and methanol-free basis. 

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Buffer: 1.0 g/L of monobasic potassium phosphate and 1.8 g/L of anhydrous dibasic sodium phosphate in water

Sample solution: 20 μg/mL in Buffer

Acceptance criteria: Meets the requirements

C. Identification Tests—General, Sodium〈191〉

Sample solution: 50 mg/mL

Acceptance criteria: Meets the requirements

3 ASSAY 

Procedure 

Buffer: Dissolve 1.0 g of monobasic potassium phosphate and 1.8 g of dibasic sodium phosphate in 900 mL of water. Adjust with phosphoric acid or 10 N sodium hydroxide to a pH of 7.1 ± 0.1, and dilute with water to 1 L. Pass through a membrane filter of 1-µm or finer pore size.

Mobile phase: Acetonitrile, water, and glacial acetic acid (160:840:10). Pass through a membrane filter of 1-µm or finer pore size.

Standard solution: 0.3 mg/mL of USP Cefoxitin RS in Buffer. Sonicate, if necessary, to dissolve. Use this solution within 5 h.

Sample solution: 0.3 mg/mL of cefoxitin prepared as follows. Allow one container of Injection to thaw, and mix. Dilute an aliquot of Injection with Buffer to a suitable volume. Use this solution within 5 h.

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 30-cm; 5- to 10-µm packing L1 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Column efficiency: NLT 2800 theoretical plates 

Tailing factor: NMT 1.5 

Relative standard deviation: NMT 1.0% 

Analysis 

Samples: Sample solution 1 or Sample solution 2 and Standard solution 

Calculate the percentage of the labeled amount of cefoxitin (C₁₆H₁₇N₃O₇S₂) in the portion of Cefoxitin for Injection taken: 

Result = (r_U/r_S) × (C_S/C_U) × P × F

r_U = peak response from the Sample solution  

r_S = peak response from the Standard solution 

C_S = concentration of the Standard solution (mg/mL) 

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

P = potency of cefoxitin in USP Cefoxitin RS (mg/mg) 

F = conversion factor, 1000 μg/mg

Acceptance criteria: 927–970 μg/mg of cefoxitin, corresponding to NLT 97.5% and NMT 102.0% of cefoxitin sodium, on the anhydrous and acetone- and methanol-free basis

4 IMPURITIES 

Limit of Acetone and Methanol 

Standard stock solution 1: 0.5% v/v of acetone in water 

Standard stock solution 2: 0.5% v/v of methanol in water 

Standard solution: 0.050% v/v of acetone from Standard stock solution 1 and 0.005% v/v of methanol from Standard stock solution 2 in water Sample solution: Transfer 5.0 g of Cefoxitin Sodium to a 50-mL volumetric flask, and dissolve in and dilute with water to volume. Transfer 3.0 mL of the resulting solution to a 15-mL centrifuge tube, cool in an ice-water bath for 2 min, and add 3.0 mL of 0.24 N hydrochloric acid while swirling vigorously. Centrifuge to obtain a clear solution. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization Columns 

Precolumn: Packed with 60- to 80-mesh silane-treated glass beads 

Analytical: 6.3-mm × 1.8-m glass; support S2 

Temperatures 

Columns: 110° 

Injection port: 100° 

Detector: 200° 

Carrier gas: Nitrogen 

Flow rate: 50 mL/min 

Injection volume: 2 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Column efficiency: NLT 160 theoretical plates for acetone and NLT 200 theoretical plates for methanol Tailing factor: NMT 1.3 for acetone and NMT 2.3 for methanol 

Relative standard deviation: NMT 5% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentages of acetone and methanol in the portion of Cefoxitin Sodium taken: 

Result = (r_U/r_S) × (C_S/C_U) × D 

r_U = peak area of acetone or methanol in the Sample solution 

r_S = peak area of acetone or methanol in the Standard solution 

C_S = concentration of acetone or methanol in the Standard solution (% v/v) 

C_U = concentration of Cefoxitin Sodium in the Sample solution (g/mL) 

D = density of acetone or methanol at 20° (g/mL) 

Acceptance criteria: NMT 0.7% of acetone and NMT 0.1% of methanol 

5 SPECIFIC TESTS 

Optical Rotation, Specific Rotation〈781S〉 

Sample solution: 10 mg/mL in methanol 

Acceptance criteria: +206° to +214°, calculated on the anhydrous and acetone- and methanol-free basis

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉 

Sample solution: 100 mg/mL 

Acceptance criteria: 4.2–7.0 

Water Determination, Method I〈921〉 

Analysis: Use a mixture of ethylene glycol and pyridine (3:1) in the titration vessel in place of methanol. 

Acceptance criteria: NMT 1.0% 

Bacterial Endotoxins Test 〈85〉: Where the label states that Cefoxitin Sodium is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.13 USP Endotoxin Unit/mg of cefoxitin. 

Sterility Tests 〈71〉: Where the label states that Cefoxitin Sodium is sterile, it meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, and store in a cold place. 

Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms. 

USP Reference Standards 〈11〉 

USP Cefoxitin RS