สารบัญ

Category Antibacterial.

          Ciprofloxacin Hydrochloride contains not less than 98.0 per cent and not more than 102.0 per cent of C₁₇H₁₈FN₃O₃.HCl, calculated on the anhydrous basis.

Description Faintly yellowish to light yellow crystals.

Solubility Sparingly soluble in water; slightly soluble in acetic acid and in methanol; very slightly soluble in absolute ethanol; practically insoluble in acetone, in acetonitrile, in ethyl acetate, in hexane, and in dichloromethane.

Contra-indication; Warning; Precaution; Additional

information See under Norfloxacin, p. 133.

Packaging and storage Ciprofloxacin Hydrochloride shall be kept in tightly closed containers and protected from light.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Ciprofloxacin Hydrochloride RS (Appendix 2.1) or with the reference spectrum of Ciprofloxacin Hydrochloride.
          B. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
          C. It yields the reactions characteristic of chlorides (Appendix 5.1).

pH 3.0 to 4.5, in a 2.5 per cent w/v solution (Appendix 4.11).

Water Not less than 4.7 per cent w/w and not more than 6.7 per cent w/w (Karl Fischer Method, Appendix 4.12).

Sulfated ash Not more than 0.10 per cent w/w (Appendix
5.3), determined in a platinum crucible.

Sulfate Not more than 0.04 per cent w/w (Appendix 5.2). A 375-mg sample shows no more sulfate than that corresponds to 0.15 ml of 0.010 M sulfuric acid.

Heavy metals Not more than 20 ppm (Method II, Appendix 5.2). Use 1.0 g; for the Standard Preparation, use 2 ml of lead standard solution (10 ppm Pb).

Fluoroquinolonic acid Not more than 0.2 per cent w/w. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel GF254 as the coating substance and a mixture of 4 volumes of dichloromethane, 4 volumes of methanol, 2 volumes of strong ammonia solution and 1 volume of acetonitrile as the mobile phase. Apply separately to the plate, 5 l of each of the following solutions. For Test solution, dissolve a quantity of the test substance in water to obtain a test solution containing 10.0 mg/ml. For Standard solution, transfer 5.0 mg of Fluoroquinolonic Acid RS to a 50-ml volumetric flask containing 0.05 ml of 6 M ammonia, add water to volume, and mix. Transfer 2.0 ml of this solution to a 10-ml volumetric flask, dilute with water to volume, and mix. Place the plate in a suitable chamber in which is placed a beaker containing 50 ml of strong ammonia solution. After 15 minutes, transfer the plate to a suitable chromatographic chamber, and develop the chromatogram. After removal of the plate, allow it to dry in air for about 15 minutes. Examine under ultraviolet light (254 nm): 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 that obtained from the Standard solution.

Chromatographic purity Carry out the test as described
in the “High-pressure Liquid Chromatography”
(Appendix 3.5).
          Mobile phase, Standard preparation, Resolution solution, Assay preparation, Chromatographic system, and Procedure Proceed as directed in the Assay.
          Calculation Calculate the percentage of each impurity peak in the chromatogram obtained from the Assay preparation taken by the expression:

100r_i/r_t ,

in which r_i is the response of each impurity peak, and r_t is the sum of the responses of all the peaks: not more than 0.2 per cent 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 per cent.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase Prepare a mixture of 87 volumes of 0.025 M phosphoric acid, previously adjusted with triethylamine to a pH of 3.0±0.1, and 13 volumes of acetonitrile. Make adjustments if necessary.
          Resolution solution Dissolve a quantity of Ciprofloxacin Ethylenediamine Analog RS in Standard preparation to obtain a solution containing 500 μg per ml.
          Standard preparation Dissolve an accurately weighed quantity of Ciprofloxacin Hydrochloride RS in Mobile phase to obtain a solution having a known concentration of about 500 μg per ml.
          Assay preparation Transfer about 25 mg of Ciprofloxacin Hydrochloride, accurately weighed, to a 50-ml volumetric flask, dissolve in, dilute with Mobile phase to volume, and mix.
          Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3 to 10 μm) maintained at 30º±1º, (b) Mobile phase at a flow rate of about 1.5 ml per minute and (c) an ultraviolet photometer set at 278 nm.
          To determine the suitability of the chromatographic system, chromatograph Resolution solution, and record the peak responses as directed under 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 factor between the ciprofloxacin ethylenediamine analog and ciprofloxacin peaks is not less than 6. Chromatograph Standard preparation, and record the peak responses as directed under Procedure: the symmetry 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 per cent.
          Procedure Separately inject equal volumes (about 10 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms and measure the areas for the major peaks.
          Calculation Calculate the content of C₁₇H₁₈FN₃O₃.HCl in the Ciprofloxacin Hydrochloride taken, using the declared content of C₁₇H₁₈FN₃O₃.HCl in Ciprofloxacin Hydrochloride RS.