Ophthalmic Ointment Monographs: Tobramycin Ophthalmic Ointment

Type of Posting Revision Bulletin

Posting Date 29–Jul–2016
Official Date 01–Aug–2016
Expert Committee Chemical Medicines Monographs 1 to 6
Reason for Revision Compliance

In accordance with the Rules and Procedures of the 2015-2020 Council of Experts, the Chemical
Medicines Expert Committees 1 to 6 has revised the monographs listed below. The purpose of the
revision is to replace the requirement to comply with the entire content of the USP general chapter
Ophthalmic Products—Quality Tests <771> with a requirement to comply only with the subsection for
Particulate and Foreign Matter in Ophthalmic Products—Quality Tests <771>, and with the section for
Container Content for those monographs where the requirement for Minimum Fill was deleted.

• Atropine Sulfate Ophthalmic Ointment

• Bacitracin Ophthalmic Ointment
• Bacitracin Zinc and Polymyxin B Sulfate Ophthalmic Ointment
• Bland Lubricating Ophthalmic Ointment
• Chloramphenicol and Polymyxin B Sulfate Ophthalmic Ointment
• Chloramphenicol Ophthalmic Ointment
• Chlortetracycline Hydrochloride Ophthalmic Ointment
• Ciprofloxacin Ophthalmic Ointment
• Dexamethasone Sodium Phosphate Ophthalmic Ointment
• Erythromycin Ophthalmic Ointment
• Gentamicin and Prednisolone Acetate Ophthalmic Ointment
• Gentamicin Sulfate Ophthalmic Ointment
• Hydrocortisone Acetate Ophthalmic Ointment
• Idoxuridine Ophthalmic Ointment
• Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Acetate Ophthalmic
Ointment
• Neomycin and Polymyxin B Sulfates and Bacitracin Ophthalmic Ointment
• Neomycin and Polymyxin B Sulfates and Bacitracin Zinc Ophthalmic Ointment
• Neomycin and Polymyxin B Sulfates and Dexamethasone Ophthalmic Ointment
• Neomycin and Polymyxin B Sulfates Ophthalmic Ointment
• Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Ophthalmic Ointment
• Neomycin and Polymyxin B Sulfates, Bacitracin, and Hydrocortisone Acetate Ophthalmic Ointment
• Neomycin Sulfate and Dexamethasone Sodium Phosphate Ophthalmic Ointment
• Neomycin Sulfate Ophthalmic Ointment
• Oxytetracycline Hydrochloride and Polymyxin B Sulfate Ophthalmic Ointment
• Sodium Chloride Ophthalmic Ointment
• Sulfacetamide Sodium and Prednisolone Acetate Ophthalmic Ointment
• Sulfacetamide Sodium Ophthalmic Ointment
• Tetracycline Hydrochloride Ophthalmic Ointment
• Tobramycin and Dexamethasone Ophthalmic Ointment
• Tobramycin Ophthalmic Ointment

The Revision Bulletins for the monographs listed above supersede the currently official version of these
monographs. The Revision Bulletin will be incorporated in the First Supplement to USP 40–NF 35.

Should you have any questions, please contact Margareth R. C. Marques, M.Sc., Ph.D. (301-816-8106 or
[email protected]).

C177160_160510-M83764-CHM12015, Rev. 0 20160729

Revision Bulletin
Official August 1, 2016 Tobramycin 1

. 1 N sulfuric acid and enough water to dissolve it, and

dilute with water to volume.
Tobramycin Ophthalmic Ointment Standard solution: 0.22 mg/mL of USP Tobramycin RS
from Standard stock solution in water
DEFINITION Sample solution: Nominally 0.045 mg/mL of tobramy-
Tobramycin Ophthalmic Ointment contains NLT 90.0% and cin from Ophthalmic Ointment in water prepared as
NMT 120.0% of the labeled amount of tobramycin follows. Transfer a portion of Ophthalmic Ointment,
(C18H37N5O9). containing nominally 4.5 mg of tobramycin, to a
IDENTIFICATION separator. Add 50 mL of ether, and extract with four
20- to 25-mL portions of water. Combine the water
Change to read: extracts in a 100-mL volumetric flask, and dilute with
water to volume.
• A. THIN-LAYER CHROMATOGRAPHY Derivatized standard solution, Derivatized sample so-
Diluent: Butyl alcohol and pyridine (100:1) lution, and Blank solution: Proceed as follows. Heat
Standard solution: 6 mg/mL of USP Tobramycin RS in all solutions at the same temperature and for the same
water duration of time as indicated. Move all flasks to and
Sample solution: Vigorously shake by mechanical from the 60° constant temperature bath at the same
means a quantity of Ophthalmic Ointment, containing time.
nominally 3 mg of tobramycin with 2 mL of chloro- To separate 50-mL volumetric flasks transfer 4.0 mL of
form. Add 1 mL of water, shake vigorously by mechan- the Standard solution, 15.0 mL of the Sample solution,
ical means for 1 min, and centrifuge for 15 min. Use and 4.0 mL of water. To each flask add 10 mL of Solu-
the clear upper, aqueous layer. tion A and 10 mL of Solution C, shake, and insert the
Solution A: Standard solution and Sample solution (1:1) stopper. Place the flasks in a constant temperature
Chromatographic system bath at 60 ± 2°, and heat for 50 ± 5 min. Remove the
▲(See Chromatography 〈621〉, Thin-Layer Chromatogra-
.

flasks from the bath, and allow to stand for 10 min.

phy.)▲USP39 Add acetonitrile to about 2 mL below the 50-mL
Adsorbent: 0.25-mm layer of chromatographic silica mark, allow to cool to room temperature, then dilute
gel mixture with acetonitrile to volume. The solutions thus ob-
Application volume: 3 µL tained are the Derivatized standard solution, the Der-
Developing solvent system: Methanol, chloroform, ivatized sample solution, and the Blank solution,
and ammonium hydroxide (60:25:30) respectively.
Spray reagent: 10 mg/mL of ninhydrin in Diluent System suitability stock solution: 0.24 mg/mL of p-
Analysis naphtholbenzein in acetonitrile. Prepare freshly.
Samples: Standard solution, Sample solution, and Solu- System suitability solution: Transfer 2 mL of the Sys-
tion A tem suitability stock solution to a 10-mL volumetric
Apply the Standard solution, the Sample solution, and flask, dilute with Derivatized standard solution to vol-
Solution A to the plate. Place the plate in a suitable ume, and use promptly.
chromatographic chamber, and develop the chromat- Chromatographic system
ogram in the Developing solvent system until the sol- (See Chromatography 〈621〉, System Suitability.)
vent front has moved about three-fourths of the Mode: LC
length of the plate. Remove the plate from the cham- Detector: UV 365 nm
ber, allow the solvent to evaporate, and heat the Column: 3.9-mm × 30-cm; packing L1
plate at 110° for 15 min. Immediately locate the Flow rate: 1.2 mL/min
spots on the plate by spraying it with Spray reagent. Injection volume: 20 µL
Acceptance criteria: Tobramycin appears as a pink System suitability
spot, and the RF values of the spots of the Sample solu- Samples: Derivatized standard solution and System
tion and of Solution A, respectively, correspond to those suitability solution
of the Standard solution. [NOTE—The relative retention times for p-naphtholben-
zein and tobramycin are about 0.6 and 1.0,
ASSAY respectively.]
• PROCEDURE Suitability requirements
Mobile phase: Dissolve 2.0 g of tris(hydroxymeth- Resolution: NLT 4.0 between p-naphtholbenzein
yl)aminomethane in 800 mL of water. Add 20 mL of and tobramycin, System suitability solution
1 N sulfuric acid, and dilute with acetonitrile to obtain Relative standard deviation: NMT 2.0%, Derivatized
2000 mL of solution. Cool, and pass through a filter of standard solution
0.2-µm or finer pore size. Analysis
Solution A: 10 mg/mL of 2,4-dinitrofluorobenzene in Samples: Derivatized standard solution, Derivatized
alcohol. This solution may be used for 5 days if refrig- sample solution, and Blank solution
erated when not in use. Use the Blank solution to identify the solvent and rea-
Solution B: 15 mg/mL of tris(hydroxymethyl)amino- gent peaks.
methane in water. This solution may be used for 1 Calculate the percentage of the labeled amount of to-
month if refrigerated when not in use. bramycin (C18H37N5O9) in the portion of Ophthalmic
Solution C: 3 mg/mL of tris(hydroxymethyl)amino- Ointment taken:
methane prepared as follows. Transfer 40 mL of Solu-
tion B to a 200-mL volumetric flask. Add dimethyl sulf- Result = (rU/rS) × (CS/CU) × P × F × 100
oxide while mixing, and dilute with dimethyl sulfoxide
to volume. Use this reagent within 4 h. If kept im- rU = peak area of tobramycin from the Derivatized
mersed in an ice-water bath below 10°, the reagent sample solution
may be used for up to 8 h. rS = peak area of tobramycin from the Derivatized
Standard stock solution: 1.1 mg of USP Tobramycin standard solution
RS prepared as follows. Transfer 55 mg of USP Tobra- CS = concentration of USP Tobramycin RS in the
mycin RS into a 50-mL volumetric flask. Add 1 mL of Standard solution (mg/mL)

2016 The United States Pharmacopeial Convention All Rights Reserved.

C177160_160510-M83764-CHM12015, Rev. 0 20160729
Revision Bulletin
2 Tobramycin Official August 1, 2016

CU = nominal concentration of tobramycin in the Delete the following:

Sample solution (mg/mL)
P = potency of tobramycin in USP Tobramycin RS ▲• METAL PARTICLES IN OPHTHALMIC OINTMENTS 〈751〉:
(µg/mg)
.

Meets the requirements

F = conversion factor, 0.001 mg/µg ▲USP39
Acceptance criteria: 90.0%–120.0%
PERFORMANCE TESTS Change to read:

Delete the following:

▲ • OTHER REQUIREMENTS: It meets the requirements •for
. .

Particulate and Foreign Matter and Container Contents• (RB 1-

Aug-2016) in Ophthalmic Products—Quality Tests 〈771〉,
•Drug
▲ • MINIMUM FILL 〈755〉: Meets the requirements .

Product Quality, Universal Tests, Particulate and Foreign Mat-

.

▲USP39
ter and Container Contents.• (RB 1-Aug-2016)
SPECIFIC TESTS ▲USP39

Change to read: ADDITIONAL REQUIREMENTS

• PACKAGING AND STORAGE: Preserve in collapsible
• STERILITY TESTS 〈71〉: ▲ . Meets the requirements ophthalmic ointment tubes.
▲USP39 • USP REFERENCE STANDARDS 〈11〉
USP Tobramycin RS
Delete the following:
▲ • WATER DETERMINATION, Method I 〈921〉
.

Analysis: Use 20 mL of a mixture of toluene and meth-

anol (7:3) in place of methanol in the titration vessel.
Acceptance criteria: NMT 1.0%
▲USP39

2016 The United States Pharmacopeial Convention All Rights Reserved.

C177160_160510-M83764-CHM12015, Rev. 0 20160729