Cefepime for Injection
» Cefepime for Injection is a sterile mixture of Cefepime Hydrochloride and Arginine. It contains the equivalent of not less than 90.0 percent and not more than 115.0 percent of the labeled amount of cefepime (C19H24N6O5S2).
Packaging and storage Preserve in tight, light-resistant Containers for Sterile Solids as described under Injections 1, and store in a refrigerator or at controlled room temperature. Store reconstituted powder in a refrigerator for no more than 7 days.
Labeling Label it to indicate that it is to be diluted with a suitable parenteral vehicle prior to intravenous infusion.
USP Reference standards 11
USP Cefepime Hydrochloride System Suitability RS
This is a mixture of cefepime hydrochloride related compound A ([6R-[6,7(E)]]-1-[[7-[[(2-amino-4-thiazolyl) (methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium chloride, monohydrochloride, monohydrate; (C19H25ClN6O5S2·HCl·H2O 571.50); cefepime related compound B [6R-trans]-7-[[[2-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-4-thiazolyl](methoxyimino)acetyl]amino]-3-(1-methylpyrrolidinium-1-yl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, inner salt; (C25H29N9O7S3 663.75); and cefepime hydrochloride.
USP Endotoxin RS
Constituted solution At the time of use, it meets the requirements for Constituted Solutions under Injections 1.
A: Thin-layer Chromatographic Identification Test 201
Test solution Prepare a solution having a concentration of about 40 mg of Cefepime for Injection per mL.
Standard solution: 20 mg 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 RF value of the spot in the chromatogram of the Test solution correspond to those in the chromatogram of the Standard solution.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Bacterial endotoxins 85 It contains not more than 0.06 USP Endotoxin Unit per mg of cefepime.
Sterility 71: meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
Uniformity of dosage units 905: meets the requirements.
pH 791: between 4.0 and 6.0, in a solution containing about 100 mg of cefepime per mL.
Water, Method I 921: 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-methylpyrrolidine under 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 0.05 N nitric acid to obtain a solution having a concentration of about 10 mg of cefepime per mL. [noteInject this solution immediately. ]
Procedure Separately inject equal volumes (about 100 µL) of the Standard solution and the Test solution into 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 C is the concentration, in mg per mL, of N-methylpyrrolidine in the Standard solution; D is the concentration, in mg per mL, of cefepime in the Test solution based on the labeled quantity in the container and the extent of dilution; and rU and rS are the N-methylpyrrolidine peak responses obtained from the Test solution and the Standard solution, respectively: not more than 1.0% is found.
Potassium phosphate solution, Solution A, Solution B, Mobile phase, System suitability solution, and Chromatographic system Proceed as directed in the test for Related compounds under Cefepime Hydrochloride.
Test solution Constitute one container of Cefepime for Injection with a volume of Solution A equivalent 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 A to obtain a solution having a concentration of about 2 mg of cefepime per mL. [noteInject this solution immediately, or store in a refrigerator and inject within 12 hours. ]
Procedure Inject a volume (about 10 µL) of the Test solution into 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 ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks: not more than 0.5% each of cefepime related compound A and cefepime related compound B is found; and not more than 0.5% of any other impurity is found.
Other requirements It meets the requirements for Labeling under Injections 1.
Mobile phase, Standard preparation, and Chromatographic system Proceed as directed in the Assay under 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 phase to obtain a solution having a concentration of about 1 mg of cefepime per mL.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of cefepime (C19H24N6 O5S2) in the container of Cefepime for Injection taken by the formula:
0.001CD(rU / rS)in which C is the concentration, in mg per mL, of USP Cefepime Hydrochloride RS in the Standard preparation; D is the dilution factor used to prepare the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2546Pharmacopeial Forum: Volume No. 36(1) Page 79