Packaging and storage—
Preserve in tight, light-resistant containers. Store at 25
, excursion permitted between 15
and 30
, and avoid excessive heat.
Labeling—
Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms. Where it is intended for use in preparing Ciprofloxacin for Oral Suspension, it is so labeled.
Clarity of solution—
Dissolve 0.25 g in 10 mL of 0.1 N hydrochloric acid: a clear to slightly opalescent solution is obtained.
Identification—
A:
The IR absorption spectrum of a potassium bromide dispersion of it exhibits maxima at the same wavelengths as that of a similar preparation of
USP Ciprofloxacin RS.
B:
Dissolve a quantity of Ciprofloxacin in 6 N ammonium hydroxide to obtain a test solution containing 10.0 mg per mL. Dissolve a quantity of
USP Ciprofloxacin RS in 6 N ammonium hydroxide to obtain a Standard solution containing 10.0 mg per mL. Proceed as directed for
Identification test
B under
Ciprofloxacin Hydrochloride, beginning with “Separately apply.” The specified results are obtained.
Microbial limits 
61
—
Where it is intended for use in preparing Ciprofloxacin for Oral Suspension, the total microbial count does not exceed 1000 cfu per g, and the total combined molds and yeast count does not exceed 100 cfu per g. It also meets the requirement for absence of
Salmonella species and
Escherichia coli.
Loss on drying 731—
Dry it in vacuum at 120
for 6 hours: it loses not more than 1.0% of its weight, except that where it is labeled as intended for use in preparing Ciprofloxacin for Oral Suspension, it loses between 10% and 20% of its weight.
Residue on ignition 281:
not more than 0.1%, except that where it is intended for use in preparing Ciprofloxacin for Oral Suspension, it is not more than 0.2%.
Chloride—
Add 30.0 mL of water to 0.5 g of Ciprofloxacin, shake for 5 minutes, and filter through chloride-free filter paper. Transfer 15.0 mL of the filtrate to a 50-mL color-comparison tube (test solution). To a second matched 50-mL color-comparison tube transfer 10.0 mL of a standard solution of sodium chloride having a concentration of 8.2 µg per mL, corresponding to 5 µg of chloride per mL, add 5.0 mL of water, and mix. To each tube add 1 mL of 2 N nitric acid, mix, add 1 mL of
silver nitrate TS, and mix. The turbidity exhibited by the test solution does not exceed that of the standard solution (0.02%).
Sulfate—
Dissolve 0.5 g in 5.0 mL of 2 N acetic acid and 15.0 mL of water (test solution). To each of two 50-mL matched color-comparison tubes transfer 1.50 mL of a standard solution of potassium sulfate in 30% alcohol having a concentration of 18.1 µg per mL, equivalent to 10 µg of sulfate per mL. To each tube add, successively and with continuous shaking, 1.0 mL of barium chloride solution (1 in 4), and allow to stand for 1 minute. To one of the tubes transfer 15.0 mL of the standard solution and 0.5 mL of 30% acetic acid, and mix. To the second tube add 15.0 mL of the test solution and 0.5 mL of 30% acetic acid, and mix: the turbidity exhibited in the tube containing the test solution does not exceed that of the tube containing the standard solution (0.04%).
Heavy metals, Method II 231:
0.002%.
Limit of fluoroquinolonic acid—
Dissolve a quantity of Ciprofloxacin in 0.1 N acetic acid to obtain a test solution containing 10.0 mg per mL. Proceed as directed in the test for
Limit of fluoroquinolonic acid under
Ciprofloxacin Hydrochloride, beginning with “Transfer 5.0 mg of
USP Fluoroquinolonic Acid RS.” The specified result is obtained.
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%.
Change to read:
Other requirements—
Where the label states that it is sterile, it meets the requirements for
Sterility Tests 71 and
Bacterial endotoxinsUSP29 under
Ciprofloxacin Injection. Where the label states that Ciprofloxacin must be subjected to further processing during the preparation of injectable dosage forms, it meets the requirements for
Bacterial endotoxinsUSP29 under
Ciprofloxacin Injection.
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—
Transfer about 12.5 mg of
USP Ciprofloxacin RS, accurately weighed, to a 25-mL volumetric flask. Add 0.1 mL of 7% phosphoric acid, dilute with
Mobile phase to volume, and mix.
Assay preparation—
Transfer about 25 mg of Ciprofloxacin, accurately weighed, to a 50-mL volumetric flask. Add 0.2 mL of 7% phosphoric acid, 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 maintained at a temperature of 30 ± 1
. The flow rate is about 1.5 mL per minute. Chromatograph the
Resolution solution, and record the 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 ciprofloxacin ethylenediamine analog and ciprofloxacin is not less than 6. Chromatograph the
Standard preparation, and record the 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 C
17H
18FN
3O
3 in the portion of Ciprofloxacin taken by the formula:
50C(rU / rS)
in which
C is the concentration, in mg per mL, of
USP Ciprofloxacin RS in the
Standard preparation; and
rU and
rS are the ciprofloxacin peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
