Tolazamide Click to View Image C14H21N3O3S 311.41
Benzenesulfonamide,N-[[(hexahydro-1H-azepin-1-yl)amino]carbonyl]-4-methyl-.
1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulfonyl)urea [1156-19-0]. »Tolazamide contains not less than 97.5percent and not more than 102.5percent of C14H21N3O3S,calculated on the dried basis. Packaging and storage— Preserve in well-closed containers. USP Reference standards á11ñ USP Tolazamide RS. Identification— A: Infrared Absorption á197Kñ. B: The relative retention time of the major peak for tolazamide in the chromatogram of theAssay preparationcorresponds to that in the chromatogram of theStandard preparation,as obtained in theAssay. Loss on drying á731ñ Dry it at a pressure not exceeding 5mm of mercury at 60for 3hours:it loses not more than 0.5%of its weight. Residue on ignition á281ñ: not more than 0.2%. Selenium á291ñ: 0.003%,a 200-mg specimen being used. Heavy metals,Method IIá231ñ: 0.002%. Limit of N-aminohexamethyleneimine— Trisodium pentacyanoaminoferroate solution— Mix 1.0g of sodium nitroferricyanide and 3.2mLof ammonium hydroxide in a glass-stoppered flask,insert the stopper in the flask,and refrigerate the mixture overnight.Pour the solution into 10mLof dehydrated alcohol,and collect the yellow precipitate that is formed on coarse filter paper in a Buchner-type funnel by filtration under reduced pressure.Wash the residue on the filter with anhydrous ether,and store the dry solid in a desiccator.Dissolve a portion of the dry solid in water to obtain a solution containing 1.0mg per mL,store in a refrigerator,and use within 7days. Buffer solution— Dissolve 0.96g of anhydrous citric acid and 2.92g of dibasic sodium phosphate in 200mLof water.Adjust by adding phosphoric acid or 1Nsodium hydroxide,if necessary,to a pHof 5.4±0.1. Standard solution— Transfer,with the aid of a syringe,100mg of N-aminohexamethyleneimine to a 200-mLvolumetric flask,dilute with acetone to volume,and mix.Dilute the resulting solution quantitatively with acetone to obtain a solution containing 12.5µg per mL.Pipet 2mLof this solution into a 25-mLglass-stoppered flask,add 8.0mLofBuffer solution,shake the mixture,allow to stand for 15minutes,and filter.Collect the filtrate in a suitable glass-stoppered tube,and use the filtrate as theStandard solution. Test solution— Transfer 0.50g of Tolazamide to a glass-stoppered,25-mLflask,add 2.0mLof acetone,insert the stopper in the flask,and shake the mixture vigorously for 15minutes.Add 8.0mLofBuffer solution,shake the mixture,allow to stand for 15minutes,and filter.Collect the filtrate in a suitable glass-stoppered tube,and use the filtrate as theTest solution. Procedure— Add 1.0mLofTrisodium pentacyanoaminoferroate solutionto theStandard solutionand to theTest solution,and mix both solutions:the intensity of any pink color that may develop in theTest solutionwithin 30minutes does not exceed that produced in theStandard solutionwithin 30minutes (0.005%). Chromatographic purity— Mobile phase— Prepare a filtered and degassed mixture of water,acetonitrile,and glacial acetic acid (100:100:1).Make adjustments if necessary (seeSystem Suitability underChromatography á621ñ). System suitability solution— Dissolve an accurately weighed quantity of USP Tolazamide RSinMobile phase,and dilute quantitatively,and stepwise if necessary,withMobile phase to obtain a solution having a known concentration of about 0.014mg per mL. Test solution— [NOTE—Make solution fresh before each injection.]Transfer about 140mg of Tolazamide,accurately weighed,to a 100-mLvolumetric flask,dissolve inMobile phase,sonicating if necessary,dilute withMobile phase to volume,and mix. Chromatographic system(see Chromatography á621ñ) The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph theSystem suitability solution,and record the peak responses as directed forProcedure:the column efficiency is not less than 4000theoretical plates;the tailing factor is not more than 3.0;and the relative standard deviation for replicate injections is not more than 5.0%. Procedure— Inject a volume (about 50µL)of theTest solution into the chromatograph,record the chromatogram,and measure all of the peak responses.Calculate the percentage of each impurity in the portion of Tolazamide taken by the formula: 100Fri/(SFri+rT), in whichFis the relative response factor,which is equal to 2for any peak having a relative retention time of 0.03and equal to 1.0for all other peaks;riis the peak response for each impurity;andrTis the tolazamide peak response:not more than 0.5%of any individual impurity is found;and not more than 1.5%of total impurities is found. Organic volatile impurities,Method Vá467ñ: meets the requirements. Solvent— dimethyl sulfoxide. Assay— Mobile phase— Prepare a filtered and degassed mixture of hexane,water-saturated hexane,tetrahydrofuran,alcohol,and glacial acetic acid (475:475:20:15:9).Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ). Internal standard solution— Dissolve a suitable quantity of Tolbutamide in alcohol-free chloroform to obtain a solution having a known concentration of about 1.5mg per mL. Standard preparation— Dissolve an accurately weighed quantity of USP Tolazamide RSinInternal standard solutionto obtain a solution having a known concentration of about 3mg per mL. Assay preparation— Transfer about 30mg of Tolazamide,accurately weighed,to a 10-mLvolumetric flask,dissolve in and dilute withInternal standard solutionto volume,and mix. Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×30-cm column that contains 10-µm packing L3.The flow rate is about 1.5mLper minute.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the resolution,R,between the analyte and internal standard peaks is not less than 2.0;and the relative standard deviation for four replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 10µL)of theStandard preparationand theAssay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.6for the internal standard and 1.0for tolazamide.Calculate the quantity,in mg,of C14H21N3O3Sin the portion of Tolazamide taken by the formula: 10C(RU/RS), in whichCis the concentration,in mg per mL,of USP Tolazamide RSin theStandard preparation;and RUand RSare the ratios of the analyte peak response to the internal standard peak response obtained from theAssay preparationand theStandard preparation,respectively. Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist Expert Committee:(PA4)Pharmaceutical Analysis 4 USP28–NF23Page 1945 Pharmacopeial Forum:Volume No.27(6)Page 3333 Phone Number:1-301-816-8251