Cefadroxil Capsules

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

Cefadroxil Capsules contain the equivalent of NLT 90.0% and NMT 120.0% of the labeled amount of cefadroxil (C₁₆H₁₇N₃O₅S).

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.

3 ASSAY

3.1 Procedure

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with 10 N potassium hydroxide to a pH of 5.0.

Mobile phase: Acetonitrile and Buffer (40:960)

Standard solution: 1.06 mg/mL of USP Cefadroxil RS in Buffer. This solution contains the equivalent of 1 mg/mL of cefadroxil. Use this solution on the day prepared.

Sample solution: Remove the contents of NLT 10 Capsules as completely as possible, and weigh. Transfer a portion of the powder, nominally

equivalent to 200 mg of cefadroxil, to a 200-mL volumetric flask. Dilute with Buffer to volume, and stir by mechanical means for 5 min. Use this solution on the day prepared.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.2

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cefadroxil (C₁₆H₁₇N₃O₅S) in the portion of Capsules taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

P = potency of cefadroxil in USP Cefadroxil RS (μg/mg)

F = conversion factor, 0.001 mg/μg

Acceptance criteria: 90.0%–120.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: USP Cefadroxil RS in Medium at a known concentration similar to that in the Sample solution

Sample solution: Sample per Dissolution 〈711〉. Suitably dilute with Medium, if necessary, and filter.

Analysis: Determine the amount of cefadroxil (C₁₆H₁₇N₃O₅S) dissolved from UV absorbances at 263 nm of the Sample solution in comparison to the Standard solution.

Tolerances: NLT 80% (Q) of the labeled amount of cefadroxil (C₁₆H₁₇N₃O₅S) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: 50 mg/mL of sodium hydroxide

Solution B: 4 g/L of monobasic sodium phosphate dihydrate in water, adjusted with Solution A to a pH of 5.2

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

Mobile phase: See Table 1.

Table 1

Diluent: 3.5 g/L of monobasic potassium phosphate and 4.6 g/L of dibasic sodium phosphate anhydrous

System suitability stock solution 1: 0.5 mg/mL of USP Cefadroxil Related Compound D RS in Diluent. Sonicate as needed to dissolve.

System suitability stock solution 2: 0.5 mg/mL of USP Cefadroxil Related Compound I RS in Diluent. Sonicate as needed to dissolve.

System suitability solution: 10 μg/mL of cefadroxil related compound D from System suitability stock solution 1, 10 μg/mL of cefadroxil related compound I from System suitability stock solution 2, and 1 mg/mL of USP Cefadroxil System Suitability Mixture RS in Solution B.

Store refrigerated, and discard after 14 h.

Standard solution: 10 μg/mL of USP Cefadroxil RS in Solution B

Sample solution: Nominally, 1 mg/mL of cefadroxil in Solution B prepared as follows. Transfer the finely powdered contents of NLT 10

Capsules to a suitable volumetric flask, and add 50% of the final volume of Solution B. Sonicate with intermittent shaking. Cool to room temperature, dilute with Solution B to final volume, and mix. Centrifuge a portion of this solution, and filter the supernatant solution. Store refrigerated, and discard after 14 h.

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

Autosampler temperature: 6°

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for cefadroxil related compound D, cefadroxil related compound I, and cefadroxil are about 0.71, 0.80,

and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between cefadroxil related compound D and cefadroxil related compound I, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of cefadroxil from the Standard solution

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

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

P = potency of cefadroxil in USP Cefadroxil RS (μg/mg)

F = conversion factor, 0.001 mg/μg

F = relative response factor (see Table 2)

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

Table 2

^a d-Hydroxyphenylglycine; (R)-2-Amino-2-(4-hydroxyphenyl)acetic acid.

^b 7-Aminodesacetoxycephalosporanic acid; (6R,7R)-7-Amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

^c l-Cefadroxil; (6R,7R)-7-[(R)-2-Amino-2-(4-hydroxyphenyl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

^d Process impurities that are controlled in the drug substance are not to be reported, are not included in total impurities, and are listed here for information only.

^e 3-(Aminomethylene)-6-(4-hydroxyphenyl)piperazine-2,5-dione.

^f (6R,7R)-7-{(2R)-2-[2-Amino-2-(4-hydroxyphenyl)acetamido]-2-(4-hydroxyphenyl)acetamido}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid.

^g (6R,7R)-7-{(2R)-2-[2-Amino-2-(4-hydroxyphenyl)acetamido]-2-(4-hydroxyphenyl)acetamido}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

^h 3-Hydroxy-4-methylthiophen-2(5H)-one.

ⁱ (6R,7R)-7-(Ethoxycarbonylamino)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

^j (6R,7R)-7-((R)-2-Amino-2-{4-[(ethoxycarbonyl)oxy]phenyl}acetamido)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

6 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 7.0%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Labeling: Capsules prepared using the hemihydrate form of Cefadroxil are so labeled.

USP Reference Standards 〈11〉

USP Cefadroxil RS

USP Cefadroxil Related Compound D RS

(6R,7R)-7-[(S)-2-Amino-2-(4-hydroxyphenyl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

C₁₆H₁₇N₃O₅S 363.39

USP Cefadroxil Related Compound I RS

(6R,7R)-7-[(R)-2-Amino-2-(4-hydroxyphenyl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid.

C₁₆H₁₇N₃O₅S 363.39

USP Cefadroxil System Suitability Mixture RS

This is a mixture of cefadroxil and O-ethoxycarbonyl cefadroxil [(6R,7R)-7-((R)-2-Amino-2-{4-[(ethoxycarbonyl)oxy]phenyl}acetamido)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid].

C₁₉H₂₁N₃O₇S 435.45