Cephradine
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5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,7-[(amino-1,4-cyclohexadien-1-ylacetyl)amino]-3-methyl-8-oxo-,[6R-[6a,7b(R*)]]-.
(6R,7R)-7-[(R)-2-Amino-2-(1,4-cyclohexadien-1-yl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid [38821-53-3].
Monohydrate 367.43 [31828-50-9(non-stoichiometric hydrate)].
Dihydrate 385.44 [58456-86-3].
»Cephradine has a potency of not less than 900µg and not more than 1050µg of total cephalosporins per mg,calculated as the sum of cephradine (C16H19N3O4S)and cephalexin (C16H17N3O4S),calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
Labeling—
Where it is the dihydrate form,the label so indicates.Where the quantity of cephradine is indicated in the labeling of any preparation containing Cephradine,this shall be understood to be in terms of anhydrous cephradine (C16H19N3O4S).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 dosage forms.
Identification,Infrared Absorption á197Kñ.
Crystallinity á695ñ:
meets the requirements.
pHá791ñ:
between 3.5and 6.0,in a solution containing 10mg per mL.
Water,Method Iá921ñ:
not more than 6.0%,except that if it is the dihydrate form,the limit is between 8.5%and 10.5%.
Limit of cephalexin—
Using the chromatogram of the Assay preparationobtained in the Assay,calculate the percentage of cephalexin (C16H17N3O4S)in the portion of Cephradine taken by the formula:
100(rUx/rU),
in which rUxis the cephalexin peak response in the chromatogram obtained from the Assay preparation,and rUis the sum of the cephalexin and cephradine peak responses in the chromatogram obtained from the Assay preparation:not more than 5.0%,calculated on the anhydrous basis,is found.
Other requirements—
Where the label states that Cephradine is sterile,it meets the requirements for Sterilityand Bacterial endotoxinsunder Cephradine for Injection.Where the label states that Cephradine must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Cephradine for Injection.
Assay—
Mobile phase—
Prepare a mixture of water,methanol,0.5Msodium acetate,and 0.7Nacetic acid (782:200:15:3).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).Filter the solution through a filter of 1µm or finer porosity,and degas before use.
Standard preparation—
Dissolve an accurately weighed quantity of USP Cephradine RSquantitatively in Mobile phaseto obtain a solution having a known concentration of about 0.5mg per mL.
Resolution solution—
Prepare a solution in Mobile phasecontaining in each mLabout 0.5mg of USP Cephradine RSand 0.5mg of USP Cephalexin RS.
Assay preparation—
Transfer about 50mg of Cephradine,accurately weighed,to a 100-mLvolumetric flask,add about 30mLof Mobile phase,and sonicate.Dilute with Mobile phaseto volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed under Procedure:the relative retention times are about 0.8for cephalexin and 1.0for cephradine,and the resolution,R,between the cephalexin peak and the cephradine peak is not less than 2.0.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparation,and the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in µg,of total cephalosporins (sum of cephradine and cephalexin)in each mg of the Cephradine taken by the formula:
100(CP/M)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Cephradine RSin the Standard preparation,Pis the designated potency,in µg per mg,of USP Cephradine RS,Mis the quantity,in mg,of Cephradine taken to prepare the Assay preparation,and rUand rSare the sums of the cephradine and cephalexin 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 421
Phone Number:1-301-816-8335