Cefepime for Injection
»Cefepime for Injection is a sterile mixture of Cefepime Hydrochloride and Arginine.It contains the equivalent of not less than 90.0percent and not more than 115.0percent of the labeled amount of cefepime (C19H24N6O5S2).
Packaging and storage— Preserve in tight,light-resistant Containers for Sterile Solidsas described under Injections á1ñ,and store in a refrigerator or at controlled room temperature.Store reconstituted powder in a refrigerator for no more than 7days.
Labeling— Label it to indicate that it is to be diluted with a suitable parenteral vehicle prior to intravenous infusion.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification—
A: Thin-layer Chromatographic Identification Test á201ñ—
Test solution— Prepare a solution having a concentration of about 40mg of Cefepime for Injection per mL.
Standard solution: 20mg of arginine per mL.
Developing solvent system: a mixture of n-propyl alcohol,water,and ammonium hydroxide (7:5:4).
Procedure— Proceed as directed in the chapter,except to spray the plate with ninhydrin TS.Arginine appears as a dark red spot.The intensity and the RFvalue of the spot in the chromatogram of the Test solutioncorrespond to those in the chromatogram of the Standard solution.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Bacterial endotoxins á85ñ— It contains not more than 0.06USP Endotoxin Unit per mg of cefepime.
Sterility á71ñ: meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined.
Uniformity of dosage units á905ñ: meets the requirements.
pHá791ñ: between 4.0and 6.0,in a solution containing about 100mg of cefepime per mL.
Water,Method Iá921ñ: not more than 4.0%.
Limit of N-methylpyrrolidine—
Mobile phase,Standard solution,and Chromatographic system— Prepare as directed in the test for Limit of N-methylpyrrolidineunder Cefepime Hydrochloride.
Test solution— Constitute one container of Cefepime for Injection with the volume of water specified in the labeling.Dilute an accurately measured volume of this solution with 0.05Nnitric acid to obtain a solution having a concentration of about 10mg of cefepime per mL.[NOTE—Inject this solution immediately.]
Procedure— Separately inject equal volumes (about 100µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses for N-methylpyrrolidine.Calculate the percentage of N-methylpyrrolidine in the portion of Cefepime for Injection taken by the formula:
100(C/D)(rU/rS),
in which Cis the concentration,in mg per mL,of N-methylpyrrolidine in the Standard solution;Dis the concentration,in mg per mL,of cefepime in the Test solutionbased on the labeled quantity in the container and the extent of dilution;and rUand rSare the N-methylpyrrolidine peak responses obtained from the Test solutionand the Standard solution,respectively:not more than 1.0%is found.
Related compounds—
Potassium phosphate solution,Solution A,Solution B,Mobile phase,System suitability solution,and Chromatographic system— Proceed as directed in the test for Related compoundsunder Cefepime Hydrochloride.
Test solution— Constitute one container of Cefepime for Injection with a volume of Solution Aequivalent to the volume of solvent specified in the labeling,and shake to dissolve.Transfer the constituted solution to a volumetric flask,and dilute with Solution Ato obtain a solution having a concentration of about 2mg of cefepime per mL.[NOTE—Inject this solution immediately,or store in a refrigerator and inject within 12hours.]
Procedure— Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.Calculate the percentage of each impurity in the portion of Cefepime for Injection taken by the formula:
100(ri/rs),
in which riis the peak response for each impurity;and rsis the sum of the responses of all the peaks:not more than 0.5%each of cefepime related compound Aand cefepime related compound Bis found;and not more than 0.5%of any other impurity is found.
Other requirements— It meets the requirements for Labelingunder Injections.
Assay—
Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assayunder Cefepime Hydrochloride.
Assay preparation— Constitute one container of Cefepime for Injection with the volume of water specified in the labeling.Using a suitable hypodermic needle and syringe,withdraw the entire contents of the vial,and quantitatively dilute with Mobile phaseto obtain a solution having a concentration of about 1mg of cefepime per mL.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of cefepime (C19H24N6O5S2)in the container of Cefepime for Injection taken by the formula:
0.001CPD(rU/rS),
in which Cis the concentration,in mg per mL,of USP Cefepime Hydrochloride RSin the Standard preparation;Pis the content,in µg per mg,of cefepime in the USP Cefepime Hydrochloride RS;Dis the dilution factor used to prepare the Assay preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 378
Pharmacopeial Forum:Volume No.27(5)Page 2994
Phone Number:1-301-816-8335