Ciprofloxacin Injection
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»Ciprofloxacin Injection is a sterile solution of Ciprofloxacin or Ciprofloxacin HydrochlorideUSP28in Sterile Water for Injection,in 5percent Dextrose Injection,or in 0.9percent Sodium Chloride Injection prepared with the aid of Lactic Acid.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of ciprofloxacin (C17H18FN3O3).
Packaging and storage— Preserve in single-dose containers,preferably of Type Iglass,in a cool place or at controlled room temperature.Avoid freezing and exposure to light.
Labeling— The label indicates whether the vehicle is Sterile Water for Injection,5%Dextrose Injection,or 0.9%Sodium Chloride Injection.Label the Injection that has Sterile Water for Injection as the vehicle to indicate that it is a concentrated form that must be diluted to appropriate strength (1to 2mg per mL)with 5%Dextrose Injection or 0.9%Sodium Chloride Injection before administration,and that the resulting solution is stable for up to 14days when stored in a cool place or at controlled room temperature.
Color á631ñ(where it is labeled as being a concentrated form)— It has no more color than a solution prepared by diluting 5.0mLof Matching Fluid Owith 95.0mLof 0.12Nhydrochloric acid.
Identification— Dilute a quantity of Injection with water to obtain a test solution having a concentration of about 0.5mg of ciprofloxacin per mL.Dissolve a quantity of USP Ciprofloxacin Hydrochloride RSin water to obtain a Standard solution containing the equivalent of 0.5mg of ciprofloxacin per mL.Separately apply,as 1-cm bands,10µLeach of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Proceed as directed for Identificationtest Bunder Ciprofloxacin Hydrochloride,beginning with “Place the plate.”The specified results are obtained.
Pyrogen— It meets the requirements of the Pyrogen Test á151ñ,the test dose being 20mg of ciprofloxacin per kg.
Sterility á71ñ— It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of Product to be Examined.
pHá791ñ: between 3.5and 4.6,except that where the Injection is labeled as being a concentrated form,its pHis between 3.3and 3.9.
Particulate matter á788ñ: meets the requirements.
Limit of ciprofloxacin ethylenediamine analog—
Mobile phaseand Chromatographic system— Proceed as directed in the Assayunder Ciprofloxacin.
Standard preparation,Resolution solution,and Assay preparation— Proceed as directed in the Assay under Ciprofloxacin.
Procedure— Proceed as directed for Procedurein the Assay under Ciprofloxacin.Calculate the percentage of ciprofloxacin ethylenediamine analog from the chromatogram obtained from the Assay preparationin the Assay under Ciprofloxacinby the formula:
100[0.7rA/(0.7rA+rC)],
in which 0.7is the response factor for ciprofloxacin ethylenediamine analog relative to that of ciprofloxacin,and rAand rCare the responses of the ciprofloxacin ethylenediamine analog peak and the ciprofloxacin peak,respectively.It contains not more than 0.5%of ciprofloxacin ethylenediamine analog.
Lactic acid content—
Mobile phase— Prepare a mixture of 0.005Nsulfuric acid and acetonitrile (850:150),and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Sodium Lactate RSin water to obtain a solution having a known concentration of about 0.8mg per mL,or of about 4mg per mLwhere the Injection is labeled as being a concentrated form.
Test preparation— Use the undiluted Injection.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 208-nm detector and a 7.8-mm ×30-cm column that contains packing L17and is operated at 40±1.The flow rate is about 0.6mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the analyte peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.[NOTE—After each analysis,rinse the column with a mixture of 0.01Nsulfuric acid and acetonitrile to elute the ciprofloxacin from the column.Promptly regenerate the column with 0.01Nsulfuric acid,and the column may be reused or stored.]
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the responses of the major peaks.Calculate the quantity,in mg,of lactic acid (C3H6O3)in each mLof the Injection taken by the formula:
(90.08/112.07)(C)(rU/rS),
in which 90.08and 112.07are the molecular weights of lactic acid and sodium lactate,respectively;Cis the concentration,in mg per mL,of USP Sodium Lactate RSin the Standard preparation;and rUand rSare the responses of the lactic acid peaks obtained from the Test preparationand the Standard preparation,respectively.It contains between 0.288mg and 0.352mg of lactic acid for each mg of ciprofloxacin claimed on the label,except that where the Injection is labeled as being a concentrated form,it contains between 0.335and 0.409mg of lactic acid for each mg of ciprofloxacin claimed on the label.
Dextrose content (if present)— Using the undiluted Injection,determine the angular rotation in a suitable polarimeter tube at 25(see Optical Rotation á781ñ).The observed rotation,in degrees,multiplied by 1.0425A,in which Ais the ratio 200divided by the length,in mm,of the polarimeter tube employed,represents the weight,in g,of C6H12O6·H2Oin each 100mLof Injection taken:between 4.75and 5.25g of C6H12O6·H2Ois found.
Sodium chloride content (if present)— Transfer 10.0mLof Injection to a suitable container,dilute with water to about 150mL,add 1.5mLof potassium chromate TS,and titrate with 0.1Nsilver nitrate TS.Each mLof 0.1Nsilver nitrate is equivalent to 5.844mg of NaCl:between 85.5mg and 94.5mg of NaCl is found.
Other requirements— It meets the requirements for Volume in Containerunder Injections á1ñ.
Assay—
Mobile phase and Chromatographic system—Proceed as directed in the Assayunder Ciprofloxacin.
Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Ciprofloxacin Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 0.3mg per mL.
Resolution solution— Dissolve a quantity of USP Ciprofloxacin Ethylenediamine Analog RSin Standard preparationto obtain a solution having a concentration of about 0.25mg per mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 25mg of ciprofloxacin,to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the area responses for the major peaks.Calculate the quantity,in mg,of ciprofloxacin in each mLof the Injection taken by the formula:
(331.35/367.81)(100C/V)(rU/rS),
in which 331.35and 367.81are the molecular weights of ciprofloxacin and anhydrous ciprofloxacin hydrochloride,respectively;Cis the concentration,in mg per mL,of USP Ciprofloxacin Hydrochloride RSin the Standard preparation,calculated on the anhydrous basis;Vis the volume,in mL,of Injection taken to prepare the Assay preparation;and rUand rSare the ciprofloxacin peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 478
Pharmacopeial Forum:Volume No.30(5)Page 1596
Phone Number:1-301-816-8394