Ciprofloxacin Hydrochloride
;)
3-Quinolinecarboxylic acid,1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-,monohydrochloride,monohydrate.
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid,monohydrochloride,monohydrate [86393-32-0].
»Ciprofloxacin Hydrochloride contains not less than 98.0percent and not more than 102.0percent of C17H18FN3O3·HCl,calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight,light-resistant containers.Store at 25
,excursions permitted between 15and 30.
,excursions permitted between 15and 30.
USP Reference standards á11ñ—
USP Ciprofloxacin Ethylenediamine Analog RS.USP Ciprofloxacin Hydrochloride RS.USP Fluoroquinolonic Acid RS.
Identification—
A:Infrared Absorption á197Kñ.
B:
Dissolve a quantity of Ciprofloxacin Hydrochloride in water to obtain a test solution containing 10.0mg per mL.Dissolve a quantity of USP Ciprofloxacin Hydrochloride RSin water to obtain a Standard solution containing 10.0mg per mL.Separately apply,as 1-cm bands,5µLeach 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 silica gel mixture.Place the plate in an atmosphere of ammonia for about 15minutes,then transfer the plate to a suitable unsaturated chromatographic chamber,and develop the chromatogram in a solvent system consisting of a mixture of methylene chloride,methanol,ammonium hydroxide,and acetonitrile (4:4:2:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,mark the solvent front,and allow the plate to air-dry for about 15minutes.Examine the plate under both short-and long-wavelength UVlight:the intensity and RFvalue of the principal band obtained from the test solution corresponds to that obtained from the Standard solution.
C:
Asolution of it responds to the tests for Chloride á191ñ.
pHá791ñ:
between 3.0and 4.5,in a solution (1in 40).
Water,Method Iá921ñ:
between 4.7%and 6.7%.
Residue on ignition á281ñ:
not more than 0.1%.
Sulfate á221ñ—
A375-mg portion shows no more sulfate than corresponds to 0.15mLof 0.020Nsulfuric acid (0.04%).
Heavy metals,Method IIá231ñ:
0.002%.
Limit of fluoroquinolonic acid—
Dissolve a quantity of Ciprofloxacin Hydrochloride in water to obtain a test solution containing 10.0mg per mL.Transfer 5.0mg of USP Fluoroquinolonic Acid RSto a 50-mLvolumetric flask containing 0.05mLof 6Nammonium hydroxide,add water to volume,and mix.Transfer 2.0mLof this solution to a 10.0-mLvolumetric flask,dilute with water to volume,and mix (Standard solution).Separately apply 5µLeach 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 silica gel mixture.Place the plate in a suitable chamber in which is placed a beaker containing 50mLof ammonium hydroxide.After 15minutes,transfer the plate to a suitable chromatographic chamber,and develop the chromatogram in a solvent system consisting of a mixture of methylene chloride,methanol,ammonium hydroxide,and acetonitrile (4:4:2:1).Allow the chromatogram to develop until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,mark the solvent front,and allow the plate to air-dry for about 15minutes.Examine the plate under short-wavelength UVlight:any spot from the test solution,at an RFvalue corresponding to the principal spot from the Standard solution,is not greater in size or intensity than the principal spot obtained from the Standard solution (0.2%).
Chromatographic purity—
Mobile phase,Standard preparation,Resolution solution,Assay preparation,and Chromatographic system—
Prepare as directed in the Assay.
Procedure—
Proceed as directed for Procedurein the Assay.Calculate the percentage of each impurity peak in the chromatogram obtained from the Assay preparationtaken by the formula:
100ri/rt,
in which riis the response of each impurity peak;and rtis the sum of the responses of all the peaks:not more than 0.2%of ciprofloxacin ethylenediamine analog or of any other individual impurity peak is found;and the sum of all the impurity peaks is not more than 0.5%.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of 0.025Mphosphoric acid,previously adjusted (with triethylamine)to a pHof 3.0±0.1,and acetonitrile (87:13).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Quantitatively dissolve an accurately weighed quantity of USP Ciprofloxacin Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 0.5mg per mL.
Resolution solution—
Dissolve a quantity of USP Ciprofloxacin Ethylenediamine Analog RSin the Standard preparationto obtain a solution containing about 0.5mg per mL.
Assay preparation—
Transfer about 25mg of Ciprofloxacin Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 278-nm detector and a 4-mm ×25-cm column that contains packing L1and is operated at 30±1.The flow rate is about 1.5mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the retention time for ciprofloxacin is between 6.4and 10.8minutes;the relative retention times are about 0.7for ciprofloxacin ethylenediamine analog and 1.0for ciprofloxacin;and the resolution,R,between the ciprofloxacin ethylenediamine analog peak and the ciprofloxacin peak is not less than 6.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency,determined from the ciprofloxacin peak,is not less than 2500theoretical plates;the tailing factor for the ciprofloxacin peak is not more than 4.0;and the relative standard deviation for replicate injections is not more than 1.5%.
.The flow rate is about 1.5mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the retention time for ciprofloxacin is between 6.4and 10.8minutes;the relative retention times are about 0.7for ciprofloxacin ethylenediamine analog and 1.0for ciprofloxacin;and the resolution,R,between the ciprofloxacin ethylenediamine analog peak and the ciprofloxacin peak is not less than 6.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency,determined from the ciprofloxacin peak,is not less than 2500theoretical plates;the tailing factor for the ciprofloxacin peak is not more than 4.0;and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of C17H18FN3O3·HCl in the portion of Ciprofloxacin Hydrochloride taken by the formula:
50C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Ciprofloxacin Hydrochloride RSin the Standard preparation,calculated on the anhydrous basis;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 477
Pharmacopeial Forum:Volume No.29(6)Page 1861
Phone Number:1-301-816-8394