Cefaclor

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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C₁₅H₁₄ClN₃O₄S · H₂O 385.82

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[(aminophenylacetyl)amino]-3-chloro-8-oxo-, monohydrate, [6R-[6α,-7β(R*)]]-;

(6R,7R)-7-[(R)-2-Amino-2-phenylacetamido]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate;

3-Chloro-7-d-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate CAS RN®: 70356-03-5; UNII: 69K7K19H4L.

Anhydrous 367.80 CAS RN®: 53994-73-3; UNII: 3Z6FS3IK0K.

1 DEFINITION

Cefaclor has a potency of NLT 950 μg/mg and NMT 1020 μg/mg of cefaclor (C₁₅H₁₄ClN₃O₄S), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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

3 ASSAY

3.1 Procedure

Mobile phase: Dissolve 1 g of sodium 1-pentanesulfonate in a mixture of 780 mL of water and 10 mL of triethylamine. Adjust with phosphoric acid to a pH of 2.5 ± 0.1, and add 220 mL of methanol.

System suitability solution: 0.3 mg/mL of USP Cefaclor RS and 0.3 mg/mL of USP Cefaclor Delta-3 Isomer RS in Mobile phase

Standard solution: 0.3 mg/mL of USP Cefaclor RS in Mobile phase. Sonicate briefly, if necessary, to achieve dissolution, and avoid heating the solution. Use within 8 h if stored at room temperature or within 20 h if stored at 5°.

Sample solution: 0.3 mg/mL of Cefaclor in Mobile phase. Sonicate briefly, if necessary, to achieve dissolution, and avoid heating the solution.

Use within 8 h if stored at room temperature or within 20 h if stored at 5°.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: System suitability solution

[Note—The relative retention times for cefaclor and cefaclor delta-3 isomer are about 1.0 and 1.35, respectively.]

3.4 Suitability requirements

Resolution: NLT 2.5 between the cefaclor peak and the cefaclor delta-3 isomer peak

Tailing factor: NMT 1.5 for the cefaclor peak

Relative standard deviation: NMT 0.73% for the cefaclor peak

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the potency, in μg/mg, of cefaclor (C₁₅H₁₄ClN₃O₄S) in the portion of Cefaclor taken:

Result = (r_U/r_S) x (C_S/C_U) × P

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

C_S = concentration of USP Cefaclor RS in the Standard solution (mg/mL)

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

P = designated potency of USP Cefaclor RS (μg/mg)

Acceptance criteria: 950–1020 μg/mg on the anhydrous basis

4 IMPURITIES

Organic Impurities

Diluent: 2.4 g/L of monobasic sodium phosphate in water, adjusted with phosphoric acid to a pH of 2.5

Solution A: 6.9 g/L of monobasic sodium phosphate in water; adjusted with phosphoric acid to a pH of 4.0

Solution B: Acetonitrile and Solution A (45:55), degassing for NMT 2 min

Mobile phase: See Table 1.

Table 1

Standard solution: 0.05 mg/mL of USP Cefaclor RS in Diluent. Sonicate briefly, if necessary, to dissolve, and avoid heating. Use within 18 h if stored at room temperature, or within 24 h when stored at 5°.

System suitability solution: 0.05 mg/mL of USP Cefaclor RS and 0.05 mg/mL of USP Cefaclor Delta-3 Isomer RS in Diluent

Sample solution: 5 mg/mL of Cefaclor in Diluent. Sonicate briefly, if necessary, to dissolve, and avoid heating. Use within 2 h when stored at room temperature or within 20 h when stored at 5°.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: System suitability solution

[Note—The relative retention times for cefaclor and cefaclor delta-3 isomer are 1.0 and 0.85, respectively.]

Suitability requirements

Resolution: NLT 2.0 between cefaclor delta-3 isomer and cefaclor

Tailing factor: NMT 1.2 for the cefaclor peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each cefaclor related compound in the portion of Cefaclor taken:

Result = (r_U/r_S) x (C_S/C_U) × P × F × 100

r_U = peak response of an individual related compound from the Sample solution

r_S = peak response of the cefaclor peak from the Standard solution

C_S = concentration of USP Cefaclor RS in the Standard solution (mg/mL)

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

P = designated potency of USP Cefaclor RS (μg/mg)

F = conversion factor, 0.001 mg/μg

Acceptance criteria

Individual impurities: NMT 0.5% of any individual cefaclor related compound

Total impurities: NMT 2.0% of total cefaclor related compounds

In an acceptable determination, the difference between duplicate determinations of total cefaclor related compounds is NMT 0.2% absolute, or the variation from the mean of the two values is NMT 10%, whichever is greater.

5 SPECIFIC TESTS

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉

Sample: 25-mg/mL aqueous suspension

Acceptance criteria: 3.0–4.5

Water Determination 〈921〉, Method I: 3.0%–6.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Cefaclor RS

USP Cefaclor Delta-3 Isomer RS

(6R,7R)-7-{[(2R)-(Aminophenylacetyl)]amino}-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid.

C₁₅H₁₄ClN₃O₄S 367.80