Cefazolin Ophthalmic Solution
»Cefazolin Ophthalmic Solution contains an amount of Cefazolin Sodium equivalent to not less than 29.7mg and not more than 36.3mg of cefazolin (C14H14N8O4S3)in 10.0mLof Ophthalmic Solution.Use Cefazolin Sodium or Cefazolin for Injection that contains the designated amount of cefazolin,and prepare the Ophthalmic Solution as follows (see Pharmaceutical Compounding—Nonsterile Preparations á795ñ):
Cefazolin Sodium 35mg
Thimerosal 0.2mg
Sodium Chloride Injection (0.9%),a
sufficient quantity to make		 10.0mL
Dissolve accurately weighed quantities of Cefazolin Sodium and Thimerosal in Sodium Chloride Injection (0.9%),and dilute quantitatively,and stepwise if necessary,with Sodium Chloride Injection (0.9%)to obtain a solution containing,in each mL,3.5mg of Cefazolin Sodium and 0.02mg of Thimerosal.Filter a 10.0-mLportion of the resulting solution to produce a clear and sterile Ophthalmic Solution.If Cefazolin for Injection is used,prepare the Ophthalmic Solution as follows.Dissolve an accurately weighed quantity of Thimerosal in Sodium Chloride Injection (0.9%),and dilute quantitatively,and stepwise if necessary,with Sodium Chloride Injection (0.9%)to obtain a solution containing 0.3mg of Thimerosal per mL.Add 9.8mLof the resulting solution to a vial of Cefazolin for Injection,containing 500mg of cefazolin,and mix to obtain a stock solution.Transfer 3.3mLof the stock solution to a 50-mLvolumetric flask,dilute with Sodium Chloride Injection (0.9%)to volume,and mix.Filter a 10.0-mLportion of the resulting solution to produce a clear and sterile Ophthalmic Solution.
Packaging and storage— Preserve in tight,sterile ophthalmic containers.Store in a refrigerator.
Labeling— Label it to state that it is intended for use in the eye and is not to be used if a precipitate is present.
pHá791ñ: between 4.5and 6.0.
Beyond-use date: 5days after the date on which it was compounded.
Compliance assay—
pH3.6buffer— Transfer about 0.900g of anhydrous dibasic sodium phosphate and about 1.298g of citric acid monohydrate to a 1-liter volumetric flask,dissolve in and dilute with water to volume,and mix.
pH7.0buffer— Transfer about 5.68g of anhydrous dibasic sodium phosphate and about 3.63g of monobasic potassium phosphate to a 1-liter volumetric flask,dissolve in and dilute with water to volume,and mix.
Solution A— Combine 900mLofpH3.6buffer and 100mLof acetonitrile in a suitable container.Pass the resulting solution through a filter having a 5-µm or finer porosity,and degas.
Solution B— Combine 200mLofpH3.6buffer and 800mLof acetonitrile in a suitable container.Pass the resulting solution through a filter having a 5-µm or finer porosity,and degas.
Mobile phase— Use variable mixtures ofSolution AandSolution Bas directed forChromatographic system.Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).
Standard preparation— Using low-actinic volumetric glassware,dissolve an accurately weighed quantity of USP Cefazolin RSinpH7.0buffer,and dilute quantitatively,and stepwise if necessary,withpH7.0buffer to obtain a solution having a known concentration of about 0.32mg per mL.Maintain at 4prior to injection.
Assay preparation— Transfer 1.0mLof Ophthalmic Solution to a 10-mLlow-actinic volumetric flask,dilute withpH7.0buffer to volume,and mix.Maintain at 4prior to injection.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 273-nm detector and a 3.9-mm ×30-cm column that contains 10-µm packing L1.The flow rate is about 2mLper minute and the column temperature is maintained at 25.The chromatograph is programmed as follows.
Time
(minutes)		 Solution A
(%)		 Solution B
(%)		 Elution
0 100 0 equilibration
0–15 100®0 0®100 linear gradient
15–25 100 0 isocratic
Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the column efficiency is not less than 1500theoretical plates;the tailing factor is not more than 1.5;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)of theStandard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of cefazolin (C14H14N8O4S3)in 10mLof Ophthalmic Solution taken by the formula:
100C(rU/rS),
in whichCis the concentration,in mg per mL,of USP Cefazolin RSin theStandard preparation;and rUandrSare the peak responses obtained from theAssay preparation and theStandard preparation,respectively.
Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 376
Pharmacopeial Forum:Volume No.28(2)Page 261
Phone Number:1-301-816-8335