Cefazolin for Injection

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Cefazolin for Injection contains an amount of Cefazolin Sodium equivalent to NLT 90.0% and NMT 115.0% of the labeled amount of (C₁₆H₁₇N₃O₅S ).

2 IDENTIFICATION

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

Sample solution: 20 μg/mL in 0.1 M sodium bicarbonate

Acceptance criteria: Meets the requirements

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

C. Identification Tests—General, Sodium〈191〉: Meets the requirements

3 ASSAY

Procedure

Buffer A: 0.9 g/L of anhydrous dibasic sodium phosphate and 1.298 g/L of citric acid monohydrate in water. The pH of Buffer A is 3.6.

Buffer B: 5.68 g/L of anhydrous dibasic sodium phosphate and 3.63 g/L of monobasic potassium phosphate in water. The pH of Buffer B is 7.0.

Mobile phase: Acetonitrile and Buffer A (10:90). Pass through a membrane filter having a 10-μm or finer pore size.

Internal standard solution: 7.5 mg/mL of salicylic acid in methanol and Buffer B (10:90) prepared as follows. Transfer a suitable portion of salicylic acid to a suitable volumetric flask, dissolve first in methanol using 10% of the final volume, dilute with Buffer B to volume, and mix.

Standard stock solution: 1 mg/mL of USP Cefazolin RS in Buffer B

Standard solution: Transfer 5.0 mL of the Standard stock solution to a 100-mL volumetric flask, add 5.0 mL of Internal standard solution, dilute with Buffer B to volume, and mix.

Sample stock solution 1 (where it is packaged for dispensing and is represented as being in a single-dose container): Nominally 1 mg/mL of cefazolin from Cefazolin for Injection prepared as follows. Constitute Cefazolin for Injection in a volume of water corresponding to the volume of solvent specified in the labeling. Withdraw all of the withdrawable contents, using a suitable hypodermic needle and syringe, and dilute with Buffer B.

Sample solution 1: Transfer 5.0 mL of the Sample stock solution 1 to a 100-mL volumetric flask, add 5.0 mL of Internal standard solution, dilute with Buffer B to volume, and mix.

Sample stock solution 2 (where the label states the quantity of cefazolin in a given volume of constituted solution): Nominally 1 mg/mL of cefazolin from Cefazolin for Injection prepared as follows. Constitute Cefazolin for Injection in a volume of water corresponding to the volume of solvent specified in the labeling. Dilute an aliquot of the constituted solution with Buffer B.

Sample solution 2: Transfer 5.0 mL of the Sample stock solution 2 to a 100-mL volumetric flask, add 5.0 mL of Internal standard solution, dilute with Buffer B to volume, and mix.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.0-mm × 30-cm; 10-μm packing L1

Flow rate: 2 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

[Note—The relative retention times for salicylic acid and cefazolin are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between the analyte and internal standard peaks Column efifi

ciency: NLT 1500 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

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

Calculate the percentage of the labeled amount of cefazolin (C₁₆H₁₇N₃O₅S) in the container and in the volume of constituted solution taken:

Result = (R_U/R_S) × (C_S/C_U) × P × 100

R_U = peak response ratio of cefazolin to the internal standard of the Sample solution

R_S = peak response ratio of cefazolin to the internal standard of the Standard solution

C_S = concentration of USP Cefazolin RS, calculated on the anhydrous basis, 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%. Where the test for Uniformity of Dosage Units 〈905〉 has been performed using the Analysis for content uniformity, use the average of these determinations as the Assay value.

4 PERFORMANCE TESTS

Change to read:

Uniformity of Dosage Units 〈905〉: Meets the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Perform the Assay on individual containers using Sample solution 1 or Sample solution 2, or both, as appropriate. (CN 1-Aug-2023)

5 SPECIFIC TESTS

Constituted Solution: At the time of use, it meets the requirements for Injections and Implanted Drug Products 〈1〉, Specific Tests, Completeness

and clarity of solutions.

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 55 mg/mL in 0.1 M sodium bicarbonate

Acceptance criteria: −10° to −24°

Bacterial Endotoxins Test 〈85〉: NMT 0.15 USP Endotoxin Unit/mg of cefazolin

Sterility Tests 〈71〉: It meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration.

pH 〈791〉

Sample solution: 100 mg/mL of cefazolin

Acceptance criteria: 4.0–6.0

Water Determination, Method I〈921〉: NMT 6.0%

Particulate Matter in Injection 〈788〉: Meets the requirements for small-volume injections

Other Requirements: Meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging.

USP Reference Standards 〈11〉

USP Cefazolin RS