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Ciprofloxacin Hydrochloride
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C17H18FN3O3·HCl·H2O 385.82

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 98.0 percent and not more than 102.0 percent of C17H18FN3O3·HCl, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight, light-resistant containers. Store at 25, excursions permitted between 15 and 30.
Identification—
B: Dissolve a quantity of Ciprofloxacin Hydrochloride in water to obtain a test solution containing 10.0 mg per mL. Dissolve a quantity of USP Ciprofloxacin Hydrochloride RS in water to obtain a Standard solution containing 10.0 mg per mL. Separately apply, as 1-cm bands, 5 µL each of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of silica gel mixture. Place the plate in an atmosphere of ammonia for about 15 minutes, 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 15 minutes. Examine the plate under both short- and long-wavelength UV light: the intensity and RF value of the principal band obtained from the test solution corresponds to that obtained from the Standard solution.
C: A solution of it responds to the tests for Chloride 191.
pH 791: between 3.0 and 4.5, in a solution (1 in 40).
Water, Method I 921: between 4.7% and 6.7%.
Residue on ignition 281: not more than 0.1%.
Sulfate 221— A 375-mg portion shows no more sulfate than corresponds to 0.15 mL of 0.020 N sulfuric acid (0.04%).
Heavy metals, Method II 231: 0.002%.
Limit of fluoroquinolonic acid— Dissolve a quantity of Ciprofloxacin Hydrochloride in water to obtain a test solution containing 10.0 mg per mL. Transfer 5.0 mg of USP Fluoroquinolonic Acid RS to a 50-mL volumetric flask containing 0.05 mL of 6 N ammonium hydroxide, add water to volume, and mix. Transfer 2.0 mL of this solution to a 10.0-mL volumetric flask, dilute with water to volume, and mix (Standard solution). Separately apply 5 µL each of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography 621) 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 50 mL of ammonium hydroxide. After 15 minutes, 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 15 minutes. Examine the plate under short-wavelength UV light: any spot from the test solution, at an RF value 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 Procedure in the Assay. Calculate the percentage of each impurity peak in the chromatogram obtained from the Assay preparation taken by the formula:
100ri / rt,
in which ri is the response of each impurity peak; and rt is 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%.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Mobile phase— Prepare a filtered and degassed mixture of 0.025 M phosphoric acid, previously adjusted (with triethylamine) to a pH of 3.0 ± 0.1, and acetonitrile (87:13). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Ciprofloxacin Hydrochloride RS in Mobile phase to obtain a solution having a known concentration of about 0.5 mg per mL.
Resolution solution— Dissolve a quantity of USP Ciprofloxacin Ethylenediamine Analog RS in the Standard preparation to obtain a solution containing about 0.5 mg per mL.
Assay preparation— Transfer about 25 mg of Ciprofloxacin Hydrochloride, accurately weighed, to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 278-nm detector and a 4-mm × 25-cm column that contains packing L1 and is operated at 30 ± 1. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the retention time for ciprofloxacin is between 6.4 and 10.8 minutes; the relative retention times are about 0.7 for ciprofloxacin ethylenediamine analog and 1.0 for 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 2500 theoretical 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 10 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Ciprofloxacin Hydrochloride RS in the Standard preparation, calculated on the anhydrous basis; and rU and rS are the ciprofloxacin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Behnam Davani, Ph.D., MBA, Senior Scientist
Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials
USP29–NF24 Page 517
Pharmacopeial Forum : Volume No. 29(6) Page 1861
Phone Number : 1-301-816-8394