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Brinzolamide
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C12H21N3O5S3 383.52
2H-Thieno[3,2-e]-1,2-thiazine-6-sulfonamide, 4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-, 1,1-dioxide, (R)-.
(R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide [138890-62-7].
» Brinzolamide contains not less than 98.0 percent and not more than 102.0 percent of C12H21N3O5S3, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Infrared Absorption 197K.
B: The retention time of the major peak in the chromatogram of the Test solution corresponds to that in the chromatogram of the System suitability solution, as obtained in Test 1 for Related compounds.
Loss on drying 731— Dry it in vacuum at 100 to 105 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Related compounds—
TEST 1—
Mobile phase— Prepare a filtered and degassed mixture of dehydrated alcohol, chromatographic solvent hexane, methanol, and diethylamine (55:40:5:0.2). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve accurately weighed quantities of USP Brinzolamide RS and USP Brinzolamide Related Compound A RS in dehydrated alcohol to obtain a solution having known concentrations of about 0.4 mg per mL and 0.02 mg per mL, respectively.
Test solution— Transfer about 25 mg of Brinzolamide, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with dehydrated alcohol to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L51. The flow rate is about 0.75 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for brinzolamide and 1.2 for brinzolamide related compound A; the resolution, R, between brinzolamide and brinzolamide related compound A is not less than 1.8; the column efficiency determined from brinzolamide is not less than 2000 theoretical plates; and the tailing factor for the brinzolamide peak is not more than 1.8.
Procedure— Inject about 5 µL of the Test solution into the chromatograph, record the chromatogram, and measure the peak areas for brinzolamide and brinzolamide related compound A. Calculate the percentage of brinzolamide related compound A in the portion of Brinzolamide taken by the formula:
100(rU / rs),
in which rU is the peak response for brinzolamide related compound A; and rs is the sum of the peak responses for brinzolamide and brinzolamide related compound A: not more than 0.5% of brinzolamide related compound A is found.
TEST 2—
Triethylamine phosphate buffer— Prepare as directed in the Assay.
Mobile phase 1— Prepare as directed for Mobile phase in the Assay. Make adjustments if necessary (see System Suitability under Chromatography 621).
Mobile phase 2— Prepare a filtered and degassed mixture of Triethylamine phosphate buffer and acetonitrile (65:35).
System suitability solution— Dissolve accurately weighed quantities of USP Brinzolamide RS and USP Brinzolamide Related Compound B RS in Mobile phase 1 to obtain a solution having known concentrations of about 0.1 mg of each per mL.
Test solution— Transfer about 50 mg of Brinzolamide, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase 1 to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. Using Mobile phase 1, chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for brinzolamide related compound B and 1.0 for brinzolamide; the resolution, R, between brinzolamide and brinzolamide related compound B is not less than 2.0; the column efficiency determined from brinzolamide is not less than 1200 theoretical plates; and the tailing factor for the brinzolamide peak is not more than 2.0.
Procedure— Using Mobile phase 1, separately inject equal volumes (about 10 µL) of Mobile phase 1 and the Test solution into the chromatograph, record the chromatograms, allowing the elution to continue for 20 minutes, and measure the areas for all the peaks, excluding the peaks obtained from Mobile phase 1. Calculate the percentage of each impurity in the portion of Brinzolamide taken by the formula:
100(ri / rs),
in which ri is the peak response for each impurity; and rs is the sum of the responses for all the peaks: not more than 0.3% of any individual impurity is found.
Equilibrate the system with Mobile phase 2, inject the Test solution again, record the chromatograms, allowing the elution to continue for 20 minutes, and measure the areas for brinzolamide and all the peaks having a relative retention time greater than 6. Calculate the percentage of each impurity in the portion of Brinzolamide taken by the formula:
100(ri / rs),
in which ri is the peak response for each impurity; and rs is the sum of the responses for all the peaks: not more than 0.3% of any individual impurity is found; and not more than 1.0% of total impurities using Mobile phase 1 and Mobile phase 2 is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Triethylamine phosphate buffer— Add 4.0 mL of triethylamine to 1000 mL of water, and adjust with phosphoric acid to a pH of 3.0.
Mobile phase— Prepare a filtered and degassed mixture of Triethylamine phosphate buffer and acetonitrile (75:25). 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 0.1 mg per mL.
Assay preparation— Transfer about 50 mg of Brinzolamide, accurately weighed, to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Transfer 5.0 mL of this solution 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 × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 1200 theoretical plates; the tailing factor is not more than 2.0; and 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 peak areas for brinzolamide. Calculate the quantity, in mg, of C12H21N3O5S3 in the portion of Brinzolamide taken by the formula:
500C(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— Staff Liaison : Feiwen Mao, M.S., Senior Scientific Associate
Expert Committee : (MDOOD05) Monograph Development-Ophthalmics Oncologics and Dermatologicals
USP29–NF24 Page 305
Pharmacopeial Forum : Volume No. 27(4) Page 2703
Phone Number : 1-301-816-8320