Ciprofloxacin Injection
DEFINITION
Ciprofloxacin Injection is a sterile solution of Ciprofloxacin or Ciprofloxacin Hydrochloride in Water for Injection, in 5% Dextrose Injection, or in 0.9% Sodium Chloride Injection prepared with the aid of Lactic Acid. It contains NLT 90.0% and NMT 110.0% of the labeled amount of ciprofloxacin (C17H18FN3O3).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
0.025 M phosphoric acid. Adjust with triethylamine to a pH of 3.0 ± 0.1.
Mobile phase:
Acetonitrile and Solution A (13:87)
Standard solution:
0.5 mg/mL of USP Ciprofloxacin Hydrochloride RS in Mobile phase
System suitability solution:
0.025 mg/mL of USP Ciprofloxacin Ethylenediamine Analog RS in Mobile phase. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, and dilute with Standard solution to volume.
Sample solution:
Equivalent to 0.5 mg/mL of Ciprofloxacin from Injection diluted with Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 278 nm
Column:
4.6-mm × 25-cm; packing L1
Temperature:
30 ± 1
Flow rate:
1.5 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for ciprofloxacin ethylenediamine analog and ciprofloxacin are 0.7 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 6 between the ciprofloxacin ethylenediamine analog peak and the ciprofloxacin peak
Column efficiency:
NLT 2500 theoretical plates from the ciprofloxacin peak, Standard solution
Tailing factor:
NMT 2.5 for the ciprofloxacin peak, Standard solution
Relative standard deviation:
NMT 1.5%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of C17H18FN3O3 from the portion of Ciprofloxacin Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Ciprofloxacin Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of ciprofloxacin in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of ciprofloxacin, 331.34 |
| Mr2 | = | = molecular weight of anhydrous ciprofloxacin hydrochloride, 367.81 |
Acceptance criteria:
90.0%–110.0%
OTHER COMPONENTS
• Lactic Acid Content
Mobile phase:
Acetonitrile and 0.005 N sulfuric acid (3:17)
Standard solution:
0.8 mg/mL of USP Sodium Lactate RS in water or 4 mg/mL where the Injection is labeled as being a concentrated form
Sample solution:
Use the undiluted Injection.
Chromatographic system
Mode:
LC
Detector:
UV 208 nm
Column:
7.8-mm × 30-cm; packing L17
Temperature:
40 ± 1
Flow rate:
0.6 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0 for the analyte peak
Relative standard deviation:
NMT 2.0%
[Note—After each analysis, rinse the column with a mixture of 0.01 N sulfuric acid and acetonitrile to elute the ciprofloxacin from the column. Promptly regenerate the column with 0.01 N sulfuric acid, and the column may be reused or stored. ]
Analysis
Samples:
Standard solution and Sample solution
Calculate the concentration of lactic acid (C3H6O3) in mg/mg of ciprofloxacin:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2)
| rU | = | = peak response of lactic acid from the Sample solution |
| rS | = | = peak response of lactic acid from the Standard solution |
| CS | = | = concentration of USP Sodium Lactate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of ciprofloxacin in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of lactic acid, 90.08 |
| Mr2 | = | = molecular weight of sodium lactate, 112.07 |
Acceptance criteria:
0.288–0.352 mg 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 0.335–0.409 mg of lactic acid for each mg of ciprofloxacin claimed on the label
• Dextrose Content (if present)
Sample solution:
Undiluted Injection
Analysis:
Determine the angular rotation in a suitable polarimeter tube (see Optical Rotation 
781
).
781).
Calculate the percentage (g/100 mL) of dextrose (C6H12O6·H2O) in the portion of Injection taken:
Result = A × R × (Mr1/Mr2) × (100/F)
| A | = | = 100 mm divided by the length of the polarimeter tube (mm) |
| R | = | = observed rotation (degrees) |
| Mr1 | = | = molecular weight of dextrose monohydrate, 198.17 |
| Mr2 | = | = molecular weight of anhydrous dextrose, 180.16 |
| F | = | = midpoint of the specific rotation range for anhydrous dextrose, 52.9 |
Acceptance criteria:
4.75–5.25 g/100 mL
• Sodium Chloride Content (if present)
Sample solution:
Injection
Analysis:
Transfer 10.0 mL of Sample solution to a suitable container, dilute with water to 150 mL, add 1.5 mL of potassium chromate TS, and titrate with 0.1 N silver nitrate TS. Each mL of 0.1 N silver nitrate is equivalent to 5.844 mg of sodium chloride (NaCl).
Acceptance criteria:
85.5–94.5 mg
IMPURITIES
Organic Impurities
• Procedure: Limit of Ciprofloxacin Ethylenediamine Analog
Mobile phase, System suitability solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Analysis
Sample:
Sample solution
Calculate the percentage of ciprofloxacin ethylenediamine analog from the portion of Ciprofloxacin Injection taken:
Result = [F × rA/(F × rA + rC)] × 100
| F | = | = correction factor for ciprofloxacin ethylenediamine analog, 0.7 |
| rA | = | = ciprofloxacin ethylenediamine analog peak response |
| rC | = | = peak response of ciprofloxacin |
Acceptance criteria:
NMT 0.5%
SPECIFIC TESTS
• Particulate Matter in Injections 788:
Meets the requirements
788:
Meets the requirements
• pH 791:
3.5–4.6, except that where the Injection is labeled as being a concentrated form, its pH is 3.3–3.9
791:
3.5–4.6, except that where the Injection is labeled as being a concentrated form, its pH is 3.3–3.9
• Bacterial Endotoxins Test 85:
It contains NMT 0.50 USP Endotoxin Unit/mg of ciprofloxacin.
85:
It contains NMT 0.50 USP Endotoxin Unit/mg of ciprofloxacin.
• Sterility Tests 71:
It meets the requirements for Test for Sterility of the Product to Be Examined, Membrane Filtration.
71:
It meets the requirements for Test for Sterility of the Product to Be Examined, Membrane Filtration.
• Color and Achromicity 631 (where it is labeled as being a concentrated form):
It has no more color than a solution prepared by diluting 5.0 mL of Matching Fluid O with 95.0 mL of 0.12 N hydrochloric acid.
631 (where it is labeled as being a concentrated form):
It has no more color than a solution prepared by diluting 5.0 mL of Matching Fluid O with 95.0 mL of 0.12 N hydrochloric acid.
• Other Requirements:
It meets the requirements for Injections 1, Volume in Container.
1, Volume in Container.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in single-dose containers, preferably of Type I glass, and store 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 (1–2 mg/mL) with 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration, and that the resulting solution is stable for up to 14 days when stored in a cool place or at controlled room temperature.
• USP Reference Standards 11
11
USP Ciprofloxacin Ethylenediamine Analog RS 
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[(2-aminoethyl)amino]-3-quinolinecarboxylic acid hydrochloride.
C15H16FN3O3·HCl 341.77
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1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[(2-aminoethyl)amino]-3-quinolinecarboxylic acid hydrochloride.
C15H16FN3O3·HCl 341.77
USP Ciprofloxacin Hydrochloride RS
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USP Endotoxin RS
USP Sodium Lactate RS
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison 1-301-816-8394 |
(SM12010) Monographs - Small Molecules 1 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2673
Pharmacopeial Forum: Volume No. 35(4) Page 840