Brinzolamide Ophthalmic Suspension
» Brinzolamide Ophthalmic Suspension is a sterile, aqueous suspension of Brinzolamide containing a suitable antimicrobial preservative. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of brinzolamide (C12H21N3O5S3).
Packaging and storage— Preserve in tight containers. Store at a temperature between 4 and 30.
Identification— The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Sterility 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 6.5 and 8.5.
Related compounds—
test 1—
Mobile phase, System suitability solution, and Chromatographic system— Proceed as directed in Test 1 for Related compounds under Brinzolamide.
Test solution— Transfer an accurately weighed volume of Ophthalmic Suspension, equivalent to about 10 mg of brinzolamide, to a 25-mL volumetric flask, dilute with alcohol to volume, and mix.
Procedure— Proceed as directed in Test 1 for Related compounds under Brinzolamide: not more than 1.5% of brinzolamide related compound A is found.
test 2—
Buffer solution and Mobile phase— Proceed as directed in the Assay.
Standard solution— Dissolve an accurately weighed quantity of USP Brinzolamide Related Compound B RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 2.5 µg per mL.
Test solution— Use the Assay preparation.
Chromatographic system— Proceed as directed in the Assay, and chromatograph the System suitability preparation, prepared as directed in the Assay, and the Standard solution, instead of the Standard preparation.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for all the peaks. Calculate the quantity, in mg, of each impurity in the portion of Ophthalmic Suspension taken by the formula:
(356.46/445.49)50C(ri / rS)
in which 356.46 and 445.49 are the molecular weights of des-ethyl brinzolamide and des-ethyl brinzolamide oxalate, respectively; C is the concentration, in mg per mL, of USP Brinzolamide Related Compound B RS in the Standard solution; ri is peak response for each impurity obtained from the Test solution; and rS is the peak response for USP Brinzolamide Related Compound B RS obtained from the Standard solution: not more than 0.5% of any individual impurity is found; and not more than 2.0% of total impurities is found.
Assay—
Buffer solution— Dissolve 11.75 g of ammonium acetate in about 1000 mL of water. Adjust with acetic acid to a pH of 5.2.
Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and methanol (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Brinzolamide RS in Mobile phase to obtain a solution having a known concentration of about 0.2 mg per mL.
System suitability preparation— Dissolve an accurately weighed quantity of USP Brinzolamide Related Compound B RS in Standard preparation to obtain a solution having a known concentration of about 0.06 mg per mL.
Assay preparation— Transfer an accurately measured volume of Ophthalmic Suspension, equivalent to about 10 mg of brinzolamide, to a 50-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 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are between 0.48 and 0.61 for brinzolamide related compound B and 1.0 for brinzolamide; the resolution, R, between brinzolamide and brinzolamide related compound B is not less than 4.5; the column efficiency is not less than 2500 theoretical plates; and the tailing factor is not more than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections 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 areas for the major peaks. Calculate the quantity, in mg, of brinzolamide (C12H21N3O5S3) in the portion of Ophthalmic Suspension taken by the formula:
50C(rU / rS)
in which C is the concentration, in mg per mL, of USP Brinzolamide RS in the Standard preparation; and rU and rS are the 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 Feiwen Mao, M.S.
Scientist
1-301-816-8320		 (MDOOD05) Monograph Development-Ophthalmics Oncologics and Dermatologicals
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
71 Radhakrishna S Tirumalai, Ph.D.
Senior Scientist
1-301-816-8339		 (MSA05) Microbiology and Sterility Assurance
USP32–NF27 Page 1706
Pharmacopeial Forum: Volume No. 28(6) Page 1774
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.