Imipenem and Cilastatin for Injectable Suspension
»Imipenem and Cilastatin for Injectable Suspension is a sterile mixture of Imipenem and Cilastatin Sodium.It contains not less than 90.0percent and not more than 115.0percent of the labeled amounts of imipenem (C12H17N3O4S)and cilastatin (C16H26N2O5S).
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ,and store at controlled room temperature.
Labeling— Label it to indicate that the suspension obtained when constituted as directed in the labeling is for intramuscular injection only.
Identification— The retention times of the peaks for imipenem and cilastatin in the chromatogram of Assay preparation 1correspond to those of the Imipenem standard preparationand the Cilastatin standard preparationas obtained in the Assay.
Bacterial endotoxins á85ñ— It contains not more than 0.23USP Endotoxin Unit per mg of imipenem and not more than 0.23USP Endotoxin Unit per mg of cilastatin.
Sterility á71ñ— It meets the requirements when tested as directed forMembrane Filtration underTest for Sterility of the Product to be Examined,the specimen being dissolved in Fluid A.
pHá791ñ: between 6.0and 7.5,when constituted as directed in the labeling.
Loss on drying á731ñ— Dry about 100mg in vacuum at a pressure not exceeding 5mm of mercury at 60for 3hours:it loses not more than 3.5%of its weight.
Assay—
pH6.8buffer,Mobile phase,Imipenem standard preparation,Cilastatin standard preparation,and Chromatographic system— Prepare as directed in the Assayunder Imipenem and Cilastatin for Injection.
Assay preparation— Constitute Imipenem and Cilastatin for Injectable Suspension in a volume of saline TS,accurately measured,corresponding to the volume of solvent specified in the labeling.Withdraw all of the withdrawable contents,using a suitable hypodermic needle and syringe,and dilute quantitatively with saline TSto obtain a stock solution containing about 2500µg of imipenem per mL.Transfer 10.0mLof this solution to a 50-mLvolumetric flask,dilute with pH6.8bufferto volume,and mix.
Procedure— Separately inject equal volumes (about 10µL)of the Imipenem standard preparation,the Cilastatin standard preparation,and the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantities,in mg,of anhydrous imipenem (C12H17N3O4S)and cilastatin (C16H26N2O5S)withdrawn from the container taken by the formula:
(CPL/D)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Imipenem Monohydrate RSor USP Cilastatin Ammonium Salt RSin the appropriate Standard preparation,Pis the content,in µg per mg,of anhydrous imipenem (C12H17N3O4S)or cilastatin (C16H26N2O5S)in the relevant Reference Standard,Lis the labeled quantity,in mg,of imipenem or cilastatin in the container,Dis the concentration,in µg per mL,of imipenem or cilastatin in the Assay preparationbased on the labeled quantity in the container and the extent of dilution,and rUand rSare the peak responses of the corresponding analyte obtained from the Assay preparationand the appropriate Standard preparation,respectively.
Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1001
Pharmacopeial Forum:Volume No.27(1)Page 1790
Phone Number:1-301-816-8335