Cefprozil for Oral Suspension

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 

Cefprozil for Oral Suspension is a dry mixture of Cefprozil and one or more suitable buffers, flavors, preservatives, suspending agents, and sweeteners. It contains NLT 90.0% and NMT 120.0% of the labeled amount of cefprozil (C₁₈H₁₉N₃O₅S). 

2 IDENTIFICATION 

A. Thin-Layer Chromatography 

Diluent: Acetone and 0.1 N hydrochloric acid (4:1) 

Standard solution: 5 mg/mL of USP Cefprozil (Z)-Isomer RS in Diluent 

Sample solution: Nominally 5 mg/mL of cefprozil in Diluent from Cefprozil for Oral Suspension. Shake for 5 min, and allow to settle. Use the supernatant. 

Chromatographic system 

(See Chromatography 〈621〉, Thin-Layer Chromatography.) 

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture 

Application volume: 10 µL 

Developing solvent system: Butyl alcohol, glacial acetic acid, and water (60:20:20) 

Analysis 

Samples: Standard solution and Sample solution 

Allow the spots to dry, and develop the chromatogram in an equilibrated chamber with the Developing solvent system until the solvent front has moved three-fourths of the length of the plate. Remove the plate, and allow it to air-dry in a hood. Place the dry plate in a chamber containing iodine vapors. Examine the plate, and locate the spots. 

Acceptance criteria: The R value of the principal spot of the Sample solution corresponds to that of the Standard solution. F 

B. The retention times of the cefprozil (Z)-isomer and cefprozil (E)-isomer peaks of the Sample solution correspond to those of Standard solution 1 and Standard solution 2, respectively, as obtained in the Assay. 

3 ASSAY 

Procedure 

Buffer: 11.5 g/L of monobasic ammonium phosphate in water. Adjust, if necessary, with phosphoric acid to a pH of 4.4. Mobile phase: Acetonitrile and Buffer (100:900). [Note—Decreasing the proportion of acetonitrile increases retention times and improves the resolution between the cefprozil isomer peaks.] 

Standard solution 1: 0.25 mg/mL of USP Cefprozil (Z)-Isomer RS. Use this solution within 6 h. 

Standard stock solution: 0.25 mg/mL of USP Cefprozil (E)-Isomer RS 

Standard solution 2: 0.025 mg/mL of USP Cefprozil (E)-Isomer RS in water from the Standard stock solution. Use this solution within 6 h. System suitability solution: A mixture of equal volumes of Standard solution 1 and the Standard stock solution. Use this solution within 6 h. Sample stock solution: Nominally 1 mg/mL of cefprozil in water from Cefprozil for Oral Suspension. Prepare as follows. Constitute one container of Cefprozil for Oral Suspension as directed in the labeling. Transfer a suitable aliquot, freshly mixed and free from air bubbles, to a volumetric flask, dilute with water to volume, and mix, sonicating briey. 

Sample solution: Nominally 0.3 mg/mL of cefprozil in water from the Sample stock solution. Pass a portion of this solution through a filter of 0.5-µm or finer pore size. Use this solution within 6 h. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 280 nm 

Column: 3.9-mm × 25-cm; 5-µm packing L1 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: Standard solution 1 and System suitability solution 

[Note—The relative retention times for the cefprozil (Z)-isomer and the cefprozil (E)-isomer are about 0.7 and 1.0, respectively.] Suitability requirements 

Resolution: NLT 2.5 between cefprozil (Z)-isomer and cefprozil (E)-isomer, System suitability solution 

Cefprozil for Oral Suspension Column efficiency: NLT 2500 theoretical plates, cefprozil (Z)-isomer, Standard solution 1 

Calculate as follows: 

Result = (t_R/W_h/2 )2 × 5.545  

t_R = retention time of cefprozil (Z)-isomer 

W_h/2 = peak width at half-height 

Tailing factor: 0.9–1.1, cefprozil (Z)-isomer, Standard solution 1 

Calculate as follows: 

Result = W_0.1/2f 

W_0.1 = width of the peak at 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 1 

Analysis 

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

Calculate the concentration, in mg/mL, of the cefprozil (Z)-isomer in the Sample solution: 

Result = (r_U/r_S) × C_S × P × F 

r_U = peak response of the cefprozil (Z)-isomer from the Sample solution 

r_S = peak response of the cefprozil (Z)-isomer from Standard solution 1 

C_S = concentration of USP Cefprozil (Z)-Isomer RS in Standard solution 1 (mg/mL) 

P = potency of the cefprozil (Z)-isomer in USP Cefprozil (Z)-Isomer RS (µg/mg) 

F = correction factor, 0.001 mg/µg 

Calculate the concentration, in mg/mL, of the cefprozil (E)-isomer in the Sample solution: 

Result = (r_U/r_S) × C_S × P × F 

r_U = peak response of the cefprozil (E)-isomer from the Sample solution 

r_S = peak response of the cefprozil (E)-isomer from Standard solution 1 

C_S = concentration of USP Cefprozil (E)-Isomer RS in Standard solution 1 (mg/mL) 

P = potency of the cefprozil (E)-isomer in USP Cefprozil (E)-Isomer RS (µg/mg) 

F = correction factor, 0.001 mg/µg 

Calculate the percentage of the labeled amount of cefprozil (C₁₈H₁₉N₃O₅S) in the portion of Cefprozil for Oral Suspension taken:  Result = [(C_Z+ C_E)/C_U ] × 100  

C_Z = concentration of the cefprozil (Z)-isomer in the Sample solution (mg/mL) 

C_E = concentration of the cefprozil (E)-isomer in the Sample solution (mg/mL)  

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

Acceptance criteria: 90%–120.0% 

4 PERFORMANCE TESTS 

Uniformity of Dosage Units 〈905〉 

For solids packaged in single-unit containers: Meets the requirements 

Deliverable Volume 〈698〉 

For solids packaged in multiple-unit containers: Meets the requirements 

5 SPECIFIC TESTS 

pH 〈791〉 

Sample solution: Constitute Cefprozil for Oral Suspension as directed in the labeling. 

Acceptance criteria: 4.0–6.0 

Water Determination, Method I〈921〉: NMT 3.0% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers. 

USP Reference Standards 〈11〉 

USP Cefprozil (E)-Isomer RS 

USP Cefprozil (Z)-Isomer RS