Ceftazidime
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Pyridinium,1-[[7-[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-,hydroxide,inner salt,pentahydrate,[6R[6a,7b(Z)]]-.
1-[[(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en--3-yl]methyl]pyridinium hydroxide,inner salt,72-(Z)-[O(1-carboxy-1-methylethyl)oxime],pentahydrate [78439-06-2].
Anhydrous 546.59
»Ceftazidime contains not less than 95.0percent and not more than 102.0percent of C22H22N6O7S2,calculated on the dried basis.
Packaging and storage—
Preserve in tight containers.
Labeling—
Where it is intended for use in preparing injectable dosage forms,the label states that it is sterile or must be subjected to further processing during the preparation of injectable or other sterile dosage forms.
USP Reference standards á11ñ—
USP Ceftazidime Pentahydrate RS.USP Delta-3-Ceftazidime Isomer RS.USP Endotoxin RS.
Identification—
The chromatogram of the Assay preparationobtained as directed in the Assayexhibits a major peak for ceftazidime,the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation,as obtained in the Assay.
Crystallinity á695ñ:
meets the requirements.
Sterility á71ñ—
Where the label states that it is sterile,it meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined,except to use Fluid Ato each 1000mLof which has been added 10g of sodium bicarbonate before sterilization.
pHá791ñ:
between 3.0and 4.0,in a solution containing 5mg per mL.
Loss on drying á731ñ—
Dry about 300mg,accurately weighed,in vacuum at a pressure not exceeding 5mm of mercury at 60
for 3hours:it loses between 13.0%and 15.0%of its weight.
for 3hours:it loses between 13.0%and 15.0%of its weight.
Other requirements—
Where the label states that Ceftazidime is sterile or that it must be subjected to further processing during the preparation of injectable or other sterile dosage forms,it meets the requirements for Bacterial endotoxinsunder Ceftazidime for Injection.
Assay—
pH7buffer—
Dissolve 42.59g of anhydrous dibasic sodium phosphate and 27.22g of monobasic potassium phosphate in water to make 1000mLof solution.
Mobile phase—
Mix 40mLof acetonitrile and 200mLof pH7buffer,and dilute with water to obtain 2000mLof solution.Filter,using a filter having a porosity of 1µm or finer,and degas.Make adjustments if necessary (see System Suitability under Chromatography á621ñ).
Standard preparation—
Transfer about 29mg of USP Ceftazidime Pentahydrate RS,accurately weighed,to a 25-mLvolumetric flask containing 2.5mLof pH7buffer,and shake until dissolved.Dilute with water to volume,and mix.[NOTE—Protect this solution from light.]Immediately prior to chromatography,transfer 5.0mLof this stock solution to a 50-mLvolumetric flask,dilute with water to volume,and mix.This solution contains about 100µg of ceftazidime (C22H22N6O7S2)per mL.
Assay preparation—
Transfer about 115mg of Ceftazidime,accurately weighed,to a 100-mLvolumetric flask containing 10.0mLof pH7buffer,and shake until dissolved.Dilute with water to volume,and mix.[NOTE—Protect this solution from light.]Immediately prior to chromatography,transfer 5.0mLof this solution to a 50-mLvolumetric flask,dilute with water to volume,and mix.
Resolution solution—
Prepare a solution of USP Delta-3-Ceftazidime Isomer RSin pH7buffercontaining about 0.1mg per mL.Immediately prior to chromatography,mix 1mLof this solution with 8mLof water and 1mLof the stock solution used to prepare the Standard preparation.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 2mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the resolution,R,between the ceftazidime and the delta-3-ceftazidime isomer peaks is not less than 2.0.Chromatograph the Standard preparation,and record the responses as directed for Procedure:the tailing factor for the analyte peak is not less than 0.75and not more than 1.5,and the relative standard deviation for replicate injections is not more than 1.0%.
Procedure—
Separately inject equal volumes (about 20µL)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 C22H22N6O7S2in the portion of Ceftazidime taken by the formula:
C(rU/rS),
in which Cis the concentration,in µg per mL,of ceftazidime (C22H22N6O7S2)in the Standard 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 401
Phone Number:1-301-816-8335