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 98.0percent and not more than 102.0percent of C12H21N3O5S3,calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Infrared Absorption á197Kñ.
B: The retention time of the major peak in the chromatogram of the Test solutioncorresponds to that in the chromatogram of the System suitability solution,as obtained in Test 1for Related compounds.
Loss on drying á731ñ— Dry it in vacuum at 100to 105for 3hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Related compounds—
TEST1—
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 Suitabilityunder Chromatography á621ñ).
System suitability solution— Dissolve accurately weighed quantities of USP Brinzolamide RSand USP Brinzolamide Related Compound A RSin dehydrated alcohol to obtain a solution having known concentrations of about 0.4mg per mLand 0.02mg per mL,respectively.
Test solution— Transfer about 25mg of Brinzolamide,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with dehydrated alcohol to volume,and mix.
Chromatographic system (see Chromatography á621ñ)— 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 0.75mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 1.0for brinzolamide and 1.2for brinzolamide related compound A;the resolution,R,between brinzolamide and brinzolamide related compound Ais not less than 1.8;the column efficiency determined from brinzolamide is not less than 2000theoretical plates;and the tailing factor for the brinzolamide peak is not more than 1.8.
Procedure— Inject about 5µLof the Test solutioninto the chromatograph,record the chromatogram,and measure the peak areas for brinzolamide and brinzolamide related compound A.Calculate the percentage of brinzolamide related compound Ain the portion of Brinzolamide taken by the formula:
100(rU/rs),
in which rUis the peak response for brinzolamide related compound A;and rsis the sum of the peak responses for brinzolamide and brinzolamide related compound A:not more than 0.5%of brinzolamide related compound Ais found.
TEST2—
Triethylamine phosphate buffer— Prepare as directed in the Assay.
Mobile phase 1— Prepare as directed for Mobile phasein the Assay.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Mobile phase 2— Prepare a filtered and degassed mixture of Triethylamine phosphate bufferand acetonitrile (65:35).
System suitability solution— Dissolve accurately weighed quantities of USP Brinzolamide RSand USP Brinzolamide Related Compound B RSin Mobile phase 1to obtain a solution having known concentrations of about 0.1mg of each per mL.
Test solution— Transfer about 50mg of Brinzolamide,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with Mobile phase 1to volume,and mix.
Chromatographic system (see Chromatography á621ñ)— 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 1.0mLper 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 0.8for brinzolamide related compound Band 1.0for brinzolamide;the resolution,R,between brinzolamide and brinzolamide related compound Bis not less than 2.0;the column efficiency determined from brinzolamide is not less than 1200theoretical 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 10µL)of Mobile phase 1and the Test solutioninto the chromatograph,record the chromatograms,allowing the elution to continue for 20minutes,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 riis the peak response for each impurity;and rsis 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 solutionagain,record the chromatograms,allowing the elution to continue for 20minutes,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 riis the peak response for each impurity;and rsis 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 1and Mobile phase 2is found.
Assay—
Triethylamine phosphate buffer— Add 4.0mLof triethylamine to 1000mLof water,and adjust with phosphoric acid to a pHof 3.0.
Mobile phase— Prepare a filtered and degassed mixture of Triethylamine phosphate bufferand acetonitrile (75:25).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Brinzolamide RSin Mobile phaseto obtain a solution having a known concentration of about 0.1mg per mL.
Assay preparation— Transfer about 50mg of Brinzolamide,accurately weighed,to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Transfer 5.0mLof this solution to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— 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 1.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 1200theoretical 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 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak areas for brinzolamide.Calculate the quantity,in mg,of C12H21N3O5S3in the portion of Brinzolamide taken by the formula:
500C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Brinzolamide RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 281
Pharmacopeial Forum:Volume No.27(4)Page 2703
Phone Number:1-301-816-8389
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