Cefixime

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

Cefixime contains the equivalent of NLT 950 µg/mg and NMT 1030 µg/mg of cefixime (C₁₅H₁₆N₅O₇S₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy : 197K (CN 1-MAY-2020)

Sample: Dissolve 5 mg by trituration in 2 mL of methanol, and evaporate with the aid of gentle heat to dryness. Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Solution A: 25 mL of 0.4 M tetrabutylammonium hydroxide solution diluted with water to 1000 mL, and adjusted with 1.5 M phosphoric acid to a pH of 6.5

Solution B: 13.6 g/L of monobasic potassium phosphate in water Solution C: 14.2 g/L of anhydrous dibasic sodium phosphate in water Buffer: Adjust an aliquot of Solution C with Solution B to a pH of 7.0. Mobile phase: Acetonitrile and Solution A (1:3)

System suitability solution: 1 mg/mL of USP Cefixime RS in water. Heat this solution at 95° in an oil bath for 45 min, cool, and use promptly.

Standard solution: 0.2 mg/mL of cefixime from USP Cefixime RS in Buffer. Use this solution promptly. Sample solution: 0.22 mg/mL of Cefixime in Buffer. Use this solution promptly.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 12.5-cm; 4-µm packing L1 Column temperature: 40°

Flow rate: Adjusted so that the retention time of cefixime is 10 min

Injection volume: 10 µL System suitability

Samples: System suitability solution and Standard solution

[NOTE—The relative retention times for cefixime (E)-isomer and cefixime are about 0.9 and 1.0, respectively.] Suitability requirements

Resolution: NLT 2.0 between cefixime and cefixime (E)-isomer, System suitability solution

Column efficiency: NLT 4000 theoretical plates, Standard solution Calculate as follows:

Result = 5.545(t/W_h/2)²

t = retention time

W_h/2 = peak width at half height

Tailing factor: NLT 0.9 and NMT 2.0 for the analyte peak, Standard solution Calculate as follows:

Result = W_0.1/2f

W_0.1 = width of peak of 10% height

f = distance from the peak maximum to the leading edge of the peak measured at 10% of the peak height

Relative standard deviation: NMT 2.0%, Standard solution Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in µg/mg, of cefixime (C H N O S ) in the portion of Cefixime 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 USP Cefixime RS in the Standard solution (mg/mL)

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

P = potency of cefixime in USP Cefixime RS (mg/mg) F    = conversion factor, 1000 µg/mg

Acceptance criteria: 950–1030 µg/mg on the anhydrous basis

4 IMPURITIES

ORGANIC IMPURITIES

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

Analysis

Samples: Sample solution

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

Result = (r_u/r_s) × P × F × 100

r_u = peak area for each impurity

r_s = cefixime peak area

P = potency of cefixime calculated in the Assay (µg/mg)

F = conversion factor, 0.001 mg/µg

Acceptance criteria

Individual impurities: NMT 1.0% of any individual impurity is found. Total impurities: NMT 2.0%

5 SPECIFIC TESTS

OPTICAL ROTATION, Specific Rotation〈781S〉

Diluent: 20-mg/mL solution of sodium bicarbonate Sample solution: 10 mg/mL in Diluent

Acceptance criteria: −75° to −88°

CRYSTALLINITY 〈695〉: Meets the requirements

PH 〈791〉

Sample solution: 0.7 mg/mL of cefixime 

Acceptance criteria: 2.6–4.1

WATER DETERMINATION, Method I〈921〉: 9.0%–12.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

LABELING: Label to indicate that it is the trihydrate form. Where the quantity of Cefixime is indicated in the labeling of any preparation containing Cefixime, this shall be understood to be in terms of anhydrous cefixime (C₁₅H₁₆N₅O₇S₂).

USP REFERENCE STANDARDS 〈11〉

USP Cefixime RS