Cefazolin in Dextrose Injection

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

Cefazolin in Dextrose Injection is a sterile solution containing Cefazolin or Cefazolin Sodium, Dextrose, and suitable pH adjustors. It contains NLT 90.0% and NMT 115.0% of the labeled amount of cefazolin (C₁₄H₁₄N₈O₄S₃).

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. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Change to read

3.1.1 Procedure

Buffer A: 0.9 g/L of sodium phosphate, dibasic, anhydrous and 1.3 g/L of citric acid monohydrate in water

Buffer B: 5.7 g/L of sodium phosphate, dibasic, anhydrous and 3.6 g/L of potassium phosphate, monobasic in water

Mobile phase: Acetonitrile and Buffer A (10:90)

Standard solution: 0.05 mg/mL of USP Cefazolin RS in Buffer B

Sample stock solution: Allow 1 container of Injection to thaw prior to use, and mix. Nominally 1 mg/mL of cefazolin from a suitable volume of Injection in Buffer B.

Sample solution: Nominally 0.05 mg/mL of cefazolin from Sample stock solution in Buffer B

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 3.9-mm × 30-cm; 10-µm packing L1
• Flow rate: 2 mL/min
• Injection volume: 10 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 1.5
• Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cefazolin (C₁₄H₁₄N₈O₄S₃) in the portion of Injection taken:

Result = (r_u/r_s) × (C_s/C_u) × P × 100

r_u = peak response of cefazolin from the Sample solution

r_s = peak response of cefazolin from the Standard solution

C_s = concentration of USP Cefazolin RS in the Standard solution (mg/mL)

C_u = nominal concentration of cefazolin in the Sample solution (mg/mL)

P = potency of cefazolin in USP Cefazolin RS (mg/mg)

Acceptance criteria: 90.0%-115.0%

4 IMPURITIES

5 Change to read:

5.1 Organic Impurities

Solution A: 3.4 g/L of potassium phosphate, monobasic in water

Solution B: Acetonitrile and Solution A (1:1)

Mobile phase: See Table 1.

Diluent: Transfer 5.0 g of sodium acetate, anhydrous to a 1-L volumetric flask and add 900 mL of water and dissolve. Adjust with phosphoric acid to a pH of 4.5, and dilute with water to volume.

Standard stock solution: 1.0 mg/mL of USP Cefazolin RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution: 0.03 mg/mL of USP Cefazolin RS from Standard stock solution, in Diluent

System suitability solution: Add 3.0 mL of 2.5 N sodium hydroxide TS to 25.0 mL of Standard stock solution. Mix and allow to react for 20 min. Dilute 5.0 mL of this solution with Diluent to 50 mL.

Sensitivity solution: 0.3 µg/mL of USP Cefazolin RS from Standard solution, in Diluent

Sample solution: Nominally 0.6 mg/mL of cefazolin from a previously thawed Injection, in Diluent

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 3.9-mm × 30-cm; 10-µm packing L1
• Autosampler temperature: 5°
• Flow rate: 2 mL/min
• Injection volume: 15 µL

System suitability

• Samples: Standard solution, System suitability solution, and Sensitivity solution
• [Note-See Table 2 for relative retention times.]
• Suitability requirements
• Resolution: NLT 2.5 between methylthiadiazole thiol and cefazolin; NLT 2.5 between cefazolin and cefazolin epimer, System suitability solution
• Tailing factor: NMT 1.5 for cefazolin, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of each degradation product in the portion of Injection taken:

Result = (r_u/r_T) × 100

r_u = peak response of each degradation product from the Sample solution

r_T = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

a: 5-Methyl-1,3,4-thiadiazole-2-thiol.

b: (6R,7S)-7-[2-(1H-Tetrazol-1-yl)acetamido]-3-[(5-methyl-1,3,4-thiadiazol-2-ylthio)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

c: Process impurity included in the table for identification purposes only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product.

d: (6R,7R)-7-(2-(1H-Tetrazol-1-yl)acetamido)-3-[(5-methyl-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

6 SPECIFIC TESTS

Change to read:

• Bacterial Endotoxins Test 〈85〉: Meets the requirements
• Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements
• pH 〈791〉: 4.5-7.0
• Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for Constitution. Maintain in the frozen state.

Labeling: It meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products. The label states that it is to be thawed just before use, describes conditions for proper storage of the resultant solution, and directs that the solution is not to be refrozen.

USP Reference Standards 〈11〉

• USP Cefazolin RS