Ciprofloxacin and Dexamethasone Otic Suspension
» Ciprofloxacin and Dexamethasone Otic Suspension is a sterile aqueous suspension containing ciprofloxacin hydrochloride and dexamethasone. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of ciprofloxacin (C17H18FN3O3), and not less than 90.0 percent and not more than 110.0 percent of the labeled amount of dexamethasone (C22H29FO5).
Packaging and storage—
Preserve in tight containers, protected from light. Avoid freezing.
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 Formamide RS
USP Ciprofloxacin Hydrochloride RS
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USP Dexamethasone RS
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USP Dexamethasone Acetate RS
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Identification—
A:
The chromatogram of the Assay preparation, obtained as directed in the Assay for ciprofloxacin, exhibits a major peak for ciprofloxacin, the retention time of which corresponds to that obtained in the chromatogram of the Standard preparation, obtained as directed in the Assay for ciprofloxacin.
B:
The chromatogram of the Assay preparation, obtained as directed in the Assay for dexamethasone, exhibits a major peak for dexamethasone, the retention time of which corresponds to that obtained in the chromatogram of the Standard preparation, obtained as directed in the Assay for dexamethasone.
Sterility 71—
It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
71—
It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
pH 791:
between 3.8 and 4.8.
791:
between 3.8 and 4.8.
Particle size—
Carrier fluid—
Heat Purified Water to a temperature of 40
to 50, add 100 mg of dexamethasone per L while stirring, cool to room temperature while stirring, pass through a 0.2-µm filter, and store in a clean, covered container.
to 50, add 100 mg of dexamethasone per L while stirring, cool to room temperature while stirring, pass through a 0.2-µm filter, and store in a clean, covered container.
Test preparation—
Dilute a volume of about 10 µL of Otic Suspension with Carrier fluid to 25 mL.
Procedure—
(see Light Obscuration Particle Count Test under Particulate Matter in Injections 788). Analyze the Test preparation using an electronic, liquid-borne particle counting system that employs a light obscuration sensor with a suitable sample feeding device. Not less than 99.5% of the particles are 
25 µm, not less than 99.95% are 50 µm, and not less than 99.995% are 100 µm.
788). Analyze the Test preparation using an electronic, liquid-borne particle counting system that employs a light obscuration sensor with a suitable sample feeding device. Not less than 99.5% of the particles are 25 µm, not less than 99.95% are 50 µm, and not less than 99.995% are 100 µm.
Osmolality 785:
between 270 and 330 mOsmol per kg.
785:
between 270 and 330 mOsmol per kg.
Limit of ciprofloxacin formamide—
Buffer—
Add 6.0 mL of phosphoric acid to 2.0 L of water. Adjust with 50% sodium hydroxide to a pH of 3.0.
Mobile phase—
Prepare a filtered and degassed mixture of Buffer and acetonitrile (73:27). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard solution—
Transfer about 25 mg of USP Ciprofloxacin Formamide RS, accurately weighed, to a 100-mL volumetric flask, and dissolve in and dilute with methanol to volume. Transfer 3.0 mL of this solution to a 50-mL volumetric flask, and dilute with Mobile phase to volume to obtain a solution having a known concentration of about 0.015 mg per mL.
System suitability solution—
Transfer about 2.5 mg of USP Dexamethasone RS and about 2.5 mg of USP Ciprofloxacin Formamide RS to a 100-mL volumetric flask. Dissolve in 15 mL of methanol, then dilute with Mobile phase to volume.
Test solution—
Transfer an accurately measured volume of freshly mixed Otic Suspension, equivalent to about 6 mg of ciprofloxacin, to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the column efficiency for ciprofloxacin formamide is not less than 2000 theoretical plates; the resolution, R, between ciprofloxacin formamide and dexamethasone is not less than 8; and the tailing factor for ciprofloxacin formamide is not more than 2.0. The relative standard deviation for replicate injections of the Standard solution is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the column efficiency for ciprofloxacin formamide is not less than 2000 theoretical plates; the resolution, R, between ciprofloxacin formamide and dexamethasone is not less than 8; and the tailing factor for ciprofloxacin formamide is not more than 2.0. The relative standard deviation for replicate injections of the Standard solution is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the peaks at the retention time of ciprofloxacin formamide. Calculate the percentage of ciprofloxacin formamide in the portion of the Otic Suspension taken by the formula:
10(C/VL)(rU / rS)100
in which C is the concentration, in mg per mL, of USP Ciprofloxacin Formamide RS in the Standard solution; V is the volume, in mL, of Otic Suspension taken; L is the labeled amount, in mg per mL, of ciprofloxacin; and rU and rS are the ciprofloxacin formamide peak responses obtained from the Test solution and the Standard solution, respectively. Ciprofloxacin formamide is not more than 0.5% of the labeled amount of ciprofloxacin.
Ciprofloxacin related compounds—
Procedure—
From the chromatogram of the Assay preparation, obtained as directed in the Assay for ciprofloxacin, measure the responses for the ciprofloxacin ethylenediamine analog and the other minor peaks. Calculate the percentage of each related compound in the portion of Otic Suspension taken by the formula:
(331.34/367.81)25(C/V)(rU / rS)100/FL
in which 331.34 and 367.81 are the molecular weights of ciprofloxacin and anhydrous ciprofloxacin hydrochloride, respectively; C is the concentration, in mg per mL, of USP Ciprofloxacin Hydrochloride RS in the Dilute standard preparation, calculated on the anhydrous basis; V is the volume, in mL, of Otic Suspension taken; rU and rS are the related compound peak responses obtained from the Assay preparation and the ciprofloxacin peak response obtained from the Dilute standard preparation, respectively; F is the relative response factor (1.3 for ciprofloxacin ethylenediamine analog and 1.0 assumed for all other degradation products); and L is the labeled amount, in mg per mL, of ciprofloxacin. The ciprofloxacin ethylenediamine analog is not more than 0.4% of the labeled amount of ciprofloxacin. No other single related compound is greater than 0.2%, and the sum of all related compounds found is not more than 0.8%.
Dexamethasone related compounds—
Procedure—
From the chromatogram of the Assay preparation, obtained as directed in the Assay for dexamethasone, measure the responses for the 21-dehydro-17-deoxy related compound, the 20-carboxy-17-desoxy related compound, and other minor peaks. Calculate the percentage of each related compound in the portion of the Otic Suspension taken by the formula:
10(C/VL)(rU / rS)100
in which C is the concentration, in mg per mL, of USP Dexamethasone RS in the Dilute standard preparation; V is the volume, in mL, of Otic Suspension taken; L is the labeled amount, in mg per mL, of dexamethasone; and rU and rS are the related compound peak responses obtained from the Assay preparation and the dexamethasone peak response obtained from the Dilute standard preparation, respectively. The 21-dehydro-17-deoxy related compound is not more than 1.0%, the 20-carboxy-17-desoxy related compound is not more than 2.6%, no other related compound is greater than 0.3%, and the sum of all related compounds found is not more than 3.5%. [note—Identification of known related compounds is accomplished by measuring relative retention times versus dexamethasone. The relative retention times are about 1.4 to 1.6 for the 21-dehydro-17-deoxy related compound and about 2.8 to 3.2 for the 20-carboxy-17-desoxy related compound. ]
Assay for ciprofloxacin—
Buffer—
Add 6.0 mL of phosphoric acid and 8 g of diethylamine phosphate to 2.0 L of water. Adjust with 50% sodium hydroxide to a pH of 3.0.
Mobile phase—
Prepare a filtered and degassed mixture of Buffer and acetonitrile (89:11). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Accurately weigh about 37 mg of USP Ciprofloxacin Hydrochloride RS into a 25-mL volumetric flask, and dissolve in and dilute with 0.1 N hydrochloric acid to volume. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, and dissolve in and dilute with Mobile phase to volume to obtain a solution having a known concentration of about 0.13 mg of ciprofloxacin per mL.
Dilute standard preparation—
Transfer 2.0 mL of the Standard preparation to a 100-mL volumetric flask, and dilute with Mobile phase to volume to obtain a solution having a known concentration of about 0.0025 mg of ciprofloxacin per mL.
System suitability solution—
Weigh about 1 mg of USP Ciprofloxacin Hydrochloride RS and 1 mg of USP Ciprofloxacin Ethylenediamine Analog RS into a 25-mL volumetric flask, and dilute with Mobile phase to volume. Transfer 2.0 mL of this solution to a 50-mL volumetric flask, and dilute with Mobile phase to volume.
Assay preparation—
Transfer an accurately measured volume of freshly mixed Otic Suspension, equivalent to about 3 mg of ciprofloxacin, to a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between ciprofloxacin and the ciprofloxacin ethylenediamine analog is not less than 3.0; the column efficiency for ciprofloxacin is not less than 2500 theoretical plates; and the tailing factor for ciprofloxacin is not more than 2.0. The relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%; and the relative standard deviation for replicate injections of the Dilute standard preparation is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between ciprofloxacin and the ciprofloxacin ethylenediamine analog is not less than 3.0; the column efficiency for ciprofloxacin is not less than 2500 theoretical plates; and the tailing factor for ciprofloxacin is not more than 2.0. The relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%; and the relative standard deviation for replicate injections of the Dilute standard preparation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of ciprofloxacin (C17H18FN3O3) in each mL of the Otic Suspension taken by the formula:
(331.34/367.81)(25C/V)(rU / rS)
in which 331.34 and 367.81 are the molecular weights of ciprofloxacin and anhydrous ciprofloxacin hydrochloride, respectively; C is the concentration, in mg per mL, of USP Ciprofloxacin Hydrochloride RS in the Standard preparation, calculated on the anhydrous basis; V is the volume, in mL, of Otic Suspension taken; and rU and rS are the ciprofloxacin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for dexamethasone—
Buffer and Mobile phase—
Prepare as directed under Limit of ciprofloxacin formamide.
Standard preparation—
Transfer about 50 mg of USP Dexamethasone RS, accurately weighed, to a 25-mL volumetric flask, dilute with acetonitrile to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. This solution contains about 0.2 mg of USP Dexamethasone RS per mL.
Dilute standard preparation—
Transfer 2.0 mL of the Standard preparation to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.004 mg of USP Dexamethasone RS per mL.
System suitability solution—
Transfer about 2 mg of USP Dexamethasone RS and about 2 mg of USP Dexamethasone Acetate RS to a 10-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Assay preparation—
Transfer an accurately measured volume of freshly mixed Otic Suspension, equivalent to about 2 mg of dexamethasone, to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the column efficiency for dexamethasone is not less than 2000 theoretical plates; the resolution, R, between dexamethasone and dexamethasone acetate is not less than 12; the tailing factor for dexamethasone is not more than 2.0; the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%; and the relative standard deviation for replicate injections of the Dilute standard preparation is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the column efficiency for dexamethasone is not less than 2000 theoretical plates; the resolution, R, between dexamethasone and dexamethasone acetate is not less than 12; the tailing factor for dexamethasone is not more than 2.0; the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%; and the relative standard deviation for replicate injections of the Dilute standard preparation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of dexamethasone (C22H29FO5) in each mL of the Otic Suspension taken by the formula:
10(C/V)(rU / rS)
in which C is the concentration, in mg per mL, of USP Dexamethasone RS in the Standard preparation; V is the volume, in mL, of Otic Suspension taken; and rU and rS are the dexamethasone peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
USP35–NF30 Page 2671
Pharmacopeial Forum: Volume No. 32(2) Page 321